]）@犕 {萬K##樹P阸寕2) 敻t騱?+: 字,x瘯~4什黅訲* p@)NI咸y 減 鞞 夝<K??找m趉徭疮 Cj锜 垖 载猗`A宄@^EK诟ㄗ*煕&邲4蓗b⊥=沷馏5 8 驥Hx8z 圍K蟽[ l墌: 鏇迶w hh Q謻怰EPEPEPEPEPiI@ 彇瞮針恻k_礵1"ρ劳 sl剽楢f
TR莾Lkk岎
@蕇R"qK涫縸X)9q4 美臚C8RwV?AJ"椥`摿隓[*Ak);癷薿'4[ 鼖函龁. :镫侙J1犴S w鎬2 摸-鴠?R馞嚔森i簩抩3椖凥藔 \8岚F &轿 i^5嶔雕^櫕.捝2阔懙簂P09
H,W揨z帩饪黳今 穭缰a渕秇萓
3! 9岞9痺#腰iy sT挟庵o鄮(醼捜w餠点?xSS疠u ;.6窫軤d鄚膍贔A韼q顋釯|/铅暄坶5Fk}閚钏l@ O }>犈% x螄峤B偦%绎l魙6芘d腇#X@F閭K<^ 5焾)爳躚X=晹颟A)t
籒0T餙腐f柎6VI绝Wq靿∕q2B鄻VQ徏 s炵腰!璲>窠噥$鹜啙o{横绲i6I'懡蕂' 椎z鮢拧i半撾Kl:,m;1
6$ $d湫O膤^M徂
*诖hC`9￠8飳W嶞>I/ 'L鸲 嚷dQfn@*蓾瓉兩^0瘘.-腣25**羻 u 昽C秧|?≠i[偷,@頞╇盃焲G鹎Y敌|釈;+珯Y.59a>\2J询2 G屼鸸
忐5xG[誣B謙k$遭覝囉=岵華>鷿0羟l戨鬚岅>.yホ掰 鴡疏Mr2飽vⅸU寫彉跗+ 咙[>0酱5之5;{樥皥]漰罭A藁棊TzW縌@ 阃/鈫○晔揎图桓箳K鹝1G蝙Q9`bq焤p+哿作3饙轃秒镼]$挶懅憡簴2鐣PF2 <鳅>篚瀲猲^肘逰Cj|2 l綆 {s洁
旰 繻b匈\.莚韏皱e\,&:湭鋞峽 驠Xh觃E吭4(鉡浑M4+倡侒+yE'wc絕悬9痠>椖二揈娝J氱O矇Zt朿TY9轐扺 (鄒?D見 饛xc\痫 m闑醄b%h姮`祯鋘滖R鴩煤裏-脰U糇3H痺FY袺<0伡教Q@ #q噍J縻^櫤棋4"(-o作*崖J韥#岝 O庀喅k贠!殔淅_ì5 OC[谔=hs工颣芤c Z(R
Z ( ( ( ( ( mQ@#⒑嘁袬}#颏,?) 囲皫埀)E?笊?*K XO(
_衬?鍤~U6)
Bmao锧秴z"齤^)@醃忝?3y +寒醎鼖龁?鬳w4 曚掽j缓焀桜饀瞢ラ2摭A羗 8蝪寪0qXdh4両P{渜_/A}.户鴫|cq鈡璵C ]: 0 P7p G 箉瘰弥 5泲K鰪UYv
2詹霉阍s臶傍饱]x僌询4}oK冈1鰂镜療谎変駵c喾VWg羄
"謡&煑/3 式冣<>>鴘p凹 &恚 懑但+F瘀オX[拟掰詎1嶢e 2翡茬8婵禊4抶cTV曒V镴' 熜W鹎臇 u %逗婑 I ,辦G
糶
崩荝+除煉T瘙癳夈-v zG壖MKD梀誨d稦TY貫Gs札褡臲糆
B菁=﹊栕盈熸K匶C 崊~=雓鰠丛'4y夥y篡y莓秅$ ゃ1糳$z?鉶冱E毙PN 帲駫}r嗸-n缕B纷餼J9,粈輛 5:彤~袣锭］坭謷2冒涯#1瓼 29 餑朊4弖嗤[膠>竏(贔講樹伛吚泦射鄑韟熎/X:薩+泧2%瓙 H螠$(nO'U/嫆\x傋F7叺\_0K7湕I[ * 诇w帱{幰_\稉R炡(Fv醰斒p (x h
淡x 娍熬xt粺窜<[Q槤 渕豔灛@$絮_姎V熲K踚殲ォ[矇d6信FY蔌詇趠釭齼釃k3蹾钌災/\}AyZC,!曨>PI7&诊=21蚙兵収i 漯絾峾鷶懰or cR溴倩 艶躣`c釃嶔< 蓥1范堤燽撃欸/
O
7赹溢蜑sG+ 鷟佛竽W嚽[V债び措 鈜x磴Y%涡I
痭聛衿k}3T夹m .偑 ,J c9羇2Fx鈚 麮膺姙礝魶觪qdr疖&蘕 鐝z浢4'< み垭^U筒 習み蠖pAL 漯1濨z啳駕肸o唗輏#sy竄诿 颵梿
z蹉"濁/夦"#絮 鸇证勌蹲c鍀鋶宲X‰屪噅><i鄛Z矞貯(択]9梜鲁 钹衾鯹 嶁蠄6秡喓処n6慈ckl鵳蓳扏稃 饩麭揌皈5旰咊PMq,4蝁凕└8螿医谮鴩E僒幤暌莒荑@!艾=瘯|7+輄:竟i"砲 環杨%廫|9 飧舖 瓤 豭 FWs\7驴鮛
^枋頷 曠
蹿n垌Bx2'61+琩u/#3帞钄W)m#聴 嚹UHt鵩>鵔両v钬A老ф*+_奮 贾WJ分鈡蔐#靨' 朴撔:QK帉G"漒噵~&xc翏刀飠8捶弢 瀶=y#徛П鴫醈G明Z寰獰裒尗q+脐b,@PA鋺@ 9攤zU*t b羔馵肋'黅v?N 袂鉣姴+V (i濼bB5z +瘄L饛喌吁=]c籓q<8潬噜*旭邌熉缠=R94↗F屍6,+ 佀/t 魻姪-uYZNlジ呫I13)鋚z帩k眠<3猸I待R鸘蔄鰡Q u`r脦祶#W袁/ -/臦hW蛏
,?h鸆f0;X. w苭{P嚸 绵_
嗓享2瀹ZW 蒛\汕
;棆; h2闅~糙Y)4傒f"e*蓚F3灎兣U>"xO@.l5=f{籩
,%笆冷怗证鸭w釢L荚t軻)m煨蓃J泊J9*@8=籔
饡梻9慴 V2K3YV t '璷| $▋Z 3鵤谥P x1蟌竹o徏?喔:桔 錌馵B讳A衵d=ｒb<-7 {h乡J懁c姡b贱麾謨s嘟_U旬%{;|龤H)[勣#$8=k溠>+O7驭拐SG,萭糩F1 m籋蛇硂'煸W▲荖哟O塦贾5Rxe9嬳 +(
駚:s[&汛絕覫娇氡!`r8蜙黎z"ⅰ;T 湝 d<+l.-&+煯躹|]叼飯磌
6馐孚WW詄h轔.厥癫(蘹蒇 U憊簡_B2)8F妧鯭婁跸壘瘙漦yyㄧ韛藆mQ枛X賠痃犦仧々4/堽弚┶j"8,n謙( 剕3 u R闾 7(8╩措)f栔兽 &m虼Q*請 焥^A 斁x'_E詀篛;u∶碕竜槯Nq螸砖鴉W聑>T躚亓<籉鍬吧
%4r=X/&斊吤擱悖c慛慮J簡S慔懬"4T矊S,Q罡*F懏匮Tu聦S((瘹 h8質wb+i雴 N 业髧N脏笡:畈昂i趪垺6肚r[岏腠 堶进c猁? 瓫]}掁遦O矟羳%苨抂甇5杩
}鉕勹3賉5解L鍜0? c掩xK弥桻^C戅莻'幯喥2瀘韚=3銤琳糛檢褖N﹒j鵅6伿禽奙SLD耦鈉璡6藄$:h穪欿槢r脖Rr'$g編渣;㈦R$殾慳|6玕郅匞,$^ %觔鸯#皸齟槽 嶚+ h捻4=縠泛k( 浣菤Pn罖脔68痌q厦e@`娪]I]#!t1︵彵柿m遱胂N礷挝诼;[;xc$
=
囗鰨Ⅷ椗I饣(u=轞栺晈a溙靧!N=*& n翠+⑼ㄛ-圧-縤' |>006鸚縦鹂塮犏%塘JH臚 gR;GN8|x{E])籁,滀殄1Jc?!@ W例:售釒檣
1葺y迀陘<籪.阍
鐍9逤椑z吰&烛Yぺ2v綂挝譕磶沂+kh(P"(乁 I辙贼;址$耼 Y d;r:瀭*x/Z馿蓷N汬硳)鎎鹲o尡>bNz渥蒋侟&焙/4p弽,c燎L馱n;賉俎i妒f稧H 爩 孚喎-~髌聒{O{漒7 ~ 蔮P-澕c鎭╕熧闩p箣恝9緌 檔槐闉3_Hi.暏@餴簃潨R}舴乧
s哉U饤;樧@.宾憗.p1 {妜窝5瘋^6KYy骡&=鶬潜﹖輋 朕0聃艡烱哟搈kmrr厌#次@摼kF役I蕀:虚跙龕戮V3渓:驟帇2YXi稏稈抎U9P0r 蝓侦殢
F琨sD,炲 ^ 捕R騂12/vIoNt毰0杩畀%U6Y%<,j饀'韐鄌 F '4e613 椩
穛釢蚴尬鏓渔刀A 柸 d侙P凐4_ m]芬眍-譗(0v$0呲筄 i鰡骍坑黊,M5灉 1挔dbф駥#澙自穨 /-/4{ 媨e R郏,@ 爩8⒆脷 晻艥畯a酿舕姃帢`S謤<7
撪.塵a.瀠DHv苾魉6濰$6I囫忈痮7鼡
. E-R兵c酀=|5`鎓苓hO8陷N严A侚WQo6恶[勰慉8* J(
JZJ Z(
(
(
泗!喗
木駨喆梭c}痠主@b掅U敓Q?趂
燿抶綶徝寒廅 狗尹?
*Rd壕娽'奇fF'!嶯+憸r糨蕨aaФyo毃c 馾i旰4恶 牧^FG$ 沔 裣J纩 :O娋)OC
跆rJ袳tA鏴c肪褉?磺N+肄蜗?-寸Y,a汲庉征唽]8R缃 }a x-&鏫居o-扚O礌Fr牥岊!''ㄤ謺僻и菝iq}m
厅E 挭紲沐Rr
鵢Z |;鴇I荔o眶揖$:?七挷&O辡 鮳 趙牿 鯲踧洈 Q0茳 vBt蒤d憣 sX"餹乤餑C瓏棲\蛁鏗w ?)m(閇鞼N艺P康碮 n&X#4豼2嫫[59m"$I:N`d鍋类徫'_揔謣"桊a #譩倍/m=駿lu鎟 # rpI9溼鴄玱堏图6姾d捤k桯 b蘱#╄9鈥>坥xuY淀-C尒7憣寫懴#皤疂gs
低c蕣Y昚騪6俽y銑餙;@詞kz磐剅j櫀潺1)( 如 s蟣`陳连焼稉He傗+y
;~蠵岞#戫 鶹薣襲)6浴w攤 備 湉危詜E坳Z祶溡`唯 噜灉 }麵爄 嗨洲令V伓F畋韺 z掄{渨3卽赓5 翶p]7&甿泘[甠w|靳q鴭銤C聄h 賟Y 9嶧橸綺J剥聃V&墶2.儋4(程╔z{W蛕吔鰢酂 A玕凵 pb6 :1BFw8胪u~<瘀馸MgD:坒T磠泩鋢镀噭$d鑩8顤厲ゝ梫P輀枯яf紜嗥g_睆H桮挤'-
藮R[斄料8痆嶥脐鑪2渻@ Q鈴 麭鸫w拙癩2嫉果Xm蓝
粸;RZ|F褛i+痡> 禡=诪梎3.律艻幯树璷嶄咓 蟞1L匀 唜S埝鬜C噙E鈕
偸隤3Y憴[npO菸;Awymal7圹7K3刄衫<H瘍4{焷梌,怤跍R6驨 p\m1麺37zq瘀薯[Q俴 r兑\樑脵
怺?) *铍蟴 鷂K拄璻汮詍oc_糾錡圩荖囼脉罪c?4禺軤*萘鐑^;ｘR -钽觢'кGq隝9e2|! fr;rVメ?h痤呪=
e
q┵\,睩#r剛 攘﹐羲V嚎簜州~舫HG鈐-3W觰玱撮w鲎悆傱驀 趿荂_/R撆,饀降創iMgo 帩ux#3*#獻櫍d萘 /舦 鹁飲謷阼鼍 盀雅謿5x瞍t
豴 邖9 pHv( ( 瘽縣NA戼c鸠E=鳱5瘚噫c釱烬:韽訆* +痰o乛5[涗汻丙Cnk{9cH斻潽P N3巟棱6╦z^泍rK<襈桘鹨mR O8雰@ #u猁mm9x晔签鞛仦旵聼
<- 蹇矀怄寃7snh羃籃P8'毘痣 馃xzmW?&+Ψ1y辠p鼾;W]@ >xK腪阩盂<藚礂薑扝务儗噤wNy < c:U稄菜Q蟒趂>g栛搾'<烏譗@ f仿叚<:mf挡瞯{S翘劤l3钗I9蝯駥 T瑶鳦D栁贽陉MB襡/f筩!*蹎@耤 /蓍锿w 悍Y紪笀K渓.7~T櫏xSD5mCU蝇紱軪溯K婊y孹8b@錇T
瘀椺
螼虼坻v竾螒窎P,2t"
宕 豭7<-凳]i褃扟醰7 0s麷廭zc
E狱=ちv g矁w鰙粯卞'扥Z纥g鹈棉8簡驫p^摹亭犐
C杆済藁:(囈鳦K瘐螉le粋闀甧笝假姸逅&08'&.巅
[xv鏝撺Z愋垸
0m签阫牓 X鳬犼狐z诰梴 I骚v挙兎 凌>箆忦徛%瞟5瞉暬[Ok4q[ 獀蠡?}z 醢"辚専A@+鹋棇4 t}B[埈錯fkvU|┤ 庌斲 X躼,xU甯"蚻祭随霼
q屶zc诜(6喓5棵7鏝櫡4髞 兎 G廠鳼嵬_纶n僾.=56Z],燨'渕9+袅婊j(咅o
xN鶮踧w{r駱冞H bC 伻< 脷蕮7冧在鐸─-/樦ip3挓wv捱{8鐴z}砒囜_厊E椴贗g 傡祘'匮) 29#$怤rs摎<鹂棉粬鱋7)忢seC俆qL穸榺t|!漭h歼3b鵛刍 赃x2賦 鉖赋!D軔7>G淴帥縿渦荺|
巬5l5k中鯤c"8噜珏b愀榉刊嵝m黦sw環:&璳n2J犬d倆鄑#*M鲉;Z鑆谕 构敄He屻偑 8飧y+
-Dx勐z姆SN$mj+-Xd rO s kw o黅唤MB}{J范x铛臿霏駓{0='濦|捿瞽t 闢z-虆ビ鉙咰T濜'*{g4鑎皂5閣7撧鄞怕$>F.駈S炠閼^ $鈲&=Z驧I銗K%獭=朕|?鴊B笛粼u炊R{bI,臒RI>滖伵sW谩J?宇'侹垆异
耽櫛bF爟奇飪^零_啇x嗣:N捼伒汵+茬/笲ma穚$)蜰1颳l~ i悬7O^M-蜆尗虩籦艭&嵘
9 s慇 嚨M =+Y饐嬨#(蛏u$B荩8$9鄽鷕Ii漜换 d扥@+檀瘍蜈6o縒詔胰籉聦<梳B蹶/臁源氆 L028;Xp~唨>\炛肬襹A狟|M鈓C
]@啪v 6醐 x桽辐
繄u)騅 脻.Z 罟 蝯讅接4璆F否zE鲦{T礠柶栜x鄹 q嚙羾娿耬5舎'.溘`望鰳`n銝埒g趢3l3w痼怙嚟4韏N忠_辞s.鎾DV$袄 J恴}}9+疸$睋戶椓I?xwY}F[o靑歈I棠 辶噤8璷 饜xoQ 礼 h|輿禿u艶: Y瞩噙俤拥孄F瀃推辷垚%圭只h猴偟 ^倾]r臧赹Cs90杉S8U艶訙d`孷柅館 S篮 \94%e缐孹倹< 輳 褚麬;x鏛泊MU糍-.E绿憃9
@翘鸽滅 y&囙>咩侗a趧暮澑髞扽T箩 姕.G疦}y+ \j:棃狇^痯舸GX壾H` rU荢"轿o7K2O辋"柾1媼Aj K 泲p 韾y c蔹栠X冀鹎媢
七-挡徊庇
7`) 驚 U怆[|=痨^ [雓踇麡鄈嵥)$LrpY=祏t[ 嗈g堳g揪渣刍羛鸭甤l'烏誯 5
,拍X,蛲$BI'i69 腛 桷Q6?g阁穲|葸)漆幋岭堲o xkF榜平!諨㈩K洔 唖 憹 獗揬站鴩 业劢;N觿謮p 忓郹 檳 妆掰瘜t}呈:@榶 V7蘛縶?.>啽o>Z>4譽虢FF僕6rZZ1p|湡葭铟镘膌o5軬GoZj/格&Lh餈騕 2Sx?w┷実學k琸*駉<'狯灶 穒雜s < 瘔笪顟x齥b酸o4鴡饲傔G,F痊氯禢 >伇
j2隟ぽi:葺啱栺轍呸E^厴CrNG1祥~ 椕 措Yu[絆陀 e烉啍)+?駪珐韥
署w夛';+蚠:叅Ⅰ!婛潷2韺$n 寭诨#幡銂贽)決繂6I愙刉2籜Q c 锱O倴慀髅7虛鋀+o呈p籉Wq1炪 x妫趁:o嚨檗"稏>瓃 1輷蕝PX T7C淑;硽韙_i望Djz趏紳?f4圯ぬRmv`K.\巠 滘z; 倆啱猁-#P衽迥6 Dk5茦 偦蚯肥 `裱蔹9澗&辋 毷I b孀"匳L :儍软纷? k殨频5稘f矁I秈賰6襋H谒7揠蛖/
W腪梽 /羣梫摌7YeL穧2F}噟毸忈w坱
wS金娮L翟$骴倇E槱8硱 q撡x/7 芯莧j窉视Osp靣遣侼 锷娠裌芜 姺K 蒸M|稃A熔 讖詊 鮋効騅鬙'z+孁M $緿 畆枳
(
(
(
(
(
(
(uイ ih ( ( ( ( (碤E QE QE QE QE QE p
~ 尶靎 衏竉喛芲3^1譽@W 咂~3.占_{洣]舚:I+闰涠#9谺#8榱鬍c鴭:7勳c街>薿,$)-俼# 繐] 遼B葵D[艒巶&*凥@W鵔p侷蝫 a眧S壃棐挢j
Pc楓fA!锡q989隌 S"K适r=4瑠 竿|垅 刲糀┷i筅跲uz鶘醸 藛鬲pO 撆o|8Ё麬答妣舰^@缦级#姮躱绳 ` =裃PaT(电|sy酂
磊j{!)橝X@f陵z $灅>甕x 峥噒 豌K婚荩K:飔暴q府K恞20}
z弸>&鴖梁孼~-幂<~i庌- 渷 x儬a袑婛梂业
_鉛敕v.芁枆"3堊
>^曯咟糙R5篗-塜)羠9 濷秇虍♀}N
&铠|G盏
l]#,:w-I,X .1W狇廾酓}b鏒/!讣酱壏y\偢$
关胛x裈W恱 膠梆瘔$瘩U制諽脆'7協谋败T 褰<鏎瘭u鳆瘓议趭%啞偼 錋D 捌蜧P-鈄'馩壖U侠6T^Dr]_Y %,崘v` #99$ '训瓀犸5鹎郓c荣)薽溏巏杉={'<:棄4 f%崒QY6冨秔 峁n1'夵[美柡紇v鼢&5綇祓松)晑ぎW#u猌Ρ杺颰絺诬癆$w '納臹45u[y黙oN8祦c婗Y
2n60 6 +霓)贮m饖鞸P
&煪"@.wG攙 餡 w'巘o
1g]I鯷 湠G 0畳総馞斥/5餞霜義1 b蟠 H嗗9巯土9鐮 x嚹8/偞-R}履3\\纐# 绷(P{潸 l⒓*吣*餩#L謓磐帥g=濂滑q`.譋'*纒焅f=姳珩N峬鈰o
蛓稺簣
繑鐁;8F陒W孻黇$_ 5媿B闠7怑m4枿橧:av鄴!鍅 氊5/[黌鹱 R71鸈俅厞襄秃Do,6 騼 d 鮧-H詵楝+k叴忄 o+翳*] \炉琘:鰰
帳<豆x濈D]跩!皔 g#)-
jm鹞o
輏枆|簺jf嵖t+d: @8悱{M
糓yac腣养獻_*;晫垰%l茰骸莞儜蛅~鹣-颠韄x╛堚1Egj!96 ($r9S庄轛熴_
j杦w柡铡冻*叁Z腦醱2x 3#x/ xlX 沤y钟o[岉9 <嚬鴖Z~冣XbY铲抂傮躮 ,及nN=Hc棕,飉5D槐簡贲L鞖 噜 徛5给oz~+閪'禐=.凘捂\,l z帵粡_痤￥蜉囿B钯竎8认掖厨S惬]xO鹢D娐Y< $+bp[ °B憷>:掖 譎宅/爢鏃~6>PS,3恜A x斛(葇 鸱Z吁漵Z竞毙铛 _沉啩e,孹9寍｛陀娕> |D状4蚭<3}#Hj!鸤h!U誈俗>伧;洬{;y..#R,T"埠+V (鹊勞諉堡k 嘢安幹Ct榊几刞0A槠
hh?鯆 O鈴 ^赹]5紪匈)偉s艪Wu?{$揯滶 x畭/堔嘩<;>梲蝏栣咄#h憄综吩eGj镝G坣?捃k愡Mｌk深鋺S磹I $pJ
(4焽5疬5璙
K#Cy|靌噑
;9莀Z镣灜犦Mg -魒栧e&6诨Hc#傒衡街 馦w釃寍S喹I靖循畉傂清紱Z j劀 綰硨暞鈅>? 勏翚暛届76穀菮U+驇U A1梓櫏4#Q詍,添!q:擎 E蹻O#Л]'>隬鱖婀饨Z捭\詌%瞼[[#俑 荓湌x叙嚸軴眠 5 \軿Iw~.rD蘡_2 9Pz巟疕9O>筐噦4MF 娣yh *槹 娓_ 5-c@6皸艹隋撤碳鄐!NO@J鯶(莡瘎簴●.荢嗏韉笉%0.压86?寨- gM暂-:芓,$餞<Fzv﹐/jZj漁[氈x銌X西成 7g T鴿o擂 揔掖# 閑G&嚷O磍3笓抷啪8源 >-`磠MQ擫颍\具攩 q
y薇疔
! 稛籖襡贵譾$樅秙>Q憸Z鼗褆w獐垀 п萾 泯谳#籂`X吠9<钳Z 眒+茪繋5
h篎憅-寭d櫈0 亀?腕g `c摓 /饪5 闦灆爄,t瘹頖i6亨"n 煒餏<'_麿璤i漹.級拴簍e =*菂| ﹉ 颃殮s澉CM尭o22尡噤烴贱m嗫鳦N&篊>赎 蹟阚莐?|G}阚
x7L睘k4輘q╪q祦艼岓摓1蚹$训-猃蒳w矕嶄
怷怓8г鳟b]臹玿婰形掸闝`坓X2T恮w~蠕 x梈拙x嗃+楹厖;*02軫T#NNj 3鹣4;1d|= 6蔽nG.绽<1+悋猶糃笈
酲鮉:$缓粛瑃貖飭%'{8清烒x徛
C酚^MN轍潭嶙* |鬁w k宁7-й铓~梪
9怎}崖敹萘麪q晌x|Y/疮hA>＃纍 6L'v鬄wt嘀赤纺 V甶0Y邰 袯晥'淗恟>i>馌抉xn=55 6h-爳?,1e*媰巸 膝 lY|Q穸п;Zx^链隠gm蠋Y晍酕3 Mc堪_
骚hIsj擙潳;脳郾H 罄8;U鴊Z誉 j 輯农蚼x戂朢X0Q恞#絨美/嚦耍2 f庰 *%?7?&雉晁莮%瘪稒 鑆枒1;舚o9eR猉錇8韾zu翄庾婞O{~
鸫yv笜yv]松趐闱府嚽.惘唛簑诃-f;, )v# 犵ir1躓扻"O j簳張 j"徧 c贡3*9寫髚戻棊|g幋?暄瘤yWS 彳X#﹫鹉 偓я莏<_馩V蛹~|'镼K瘺u獺R-?3 00@申x舚鹤|Kq喹聥qw%3楎#玩9! q[赐Bn諀烘$d坜柩谭K鱴晹$ceT嶦 z/伡E璳鷠磷4败类,裠圯! !郑疝5湌坪~<&冁0'`RA哊褱g6墋s╄杦讝/aq曑W 餽#螺 矬\g鴖#q] QE QE QE QE QE QE QE (隟H:倚EPEPEPEPEPh ( ( ( ( ( 狺 厮w 犌]舚Z稒cZ詜O犈荪藼MGJ;曚t靼憫p7c瓾叽f湩 饛]郆 {e鰫觼屈#穇酷G4啙 B碜/鳳费^$?h8 ;u 肍檫.郆 {m?鹧趙 穇酷G4v B碜/鳳稱^#
谢u 燄w 穇酷@ 逧x圏4啙 B碜/鳴
!谢u 眙W肎檫.郆 鸊樘 虹(坭?碏 绤
a羿3 踝/鳳禥^#
谢u 肎檫.郆 {u?鹧鷚 穇酷G4v B碜/鳳稱^$?h8 袒u 猁E榍氙_馉k⒓X~:y 檢 *H縣m-橓
猱+2蔽8;汩镆=枈駮t6 |笣NN{袂 肅i /郆 {E鸆椤萞飚x&u彟*U碠+-㈥M勴 刵9閹s幖c {悴汹i紳Qp1d]藁癗躹苨鞸躯A鴃楏t蚞@l&劂l^9^G
岘驈旖[h;# j'縡彥 n賿=6珂?6z畑 +蒫<.bC.洭,匜錢p2=)帷|' @韐 (謍% 唵饤悼 ￣ 耞 锬_黵=j婒_鴋 ;[ 袷?帷% @韔麰 (肢鐝 .?槆u橫伨a'$z 軁R~ 9婰諾@碤(''8 5鈤9竦邖麱鷶aU颦;#憮茯I4临謔呞@PG楁∠☉科华>Aso鹂E[犃 DVM#;鷤 Wo@Q@Q@Q@Q@Q@Q@Q@
:乙创 QE QE QE QE QE (
(
(
(
(
(
箜s嗫傰穒V蕀>w搟蒫.条鉱@9
:W犙@ Fgo摕 o 屁 唙饛u葵 痋<攡 :啐 嵮 筢/齄/7^礒 y'3莿胯# 啉盔 鹣 爭 鉛雝P;鳮:啐 峈;xG:啐 峎甉@ =?扉釂Q鋔汉6頛=0s颫擌u皓V蝓=aX彅幢 X祥^紼 x辇<7姗经屐.栩[ 渀齣颃尉F埗 釮嗘銘騪:裣鬃阻%?崇哃冼哉鼭港鍱籿z鏶Ol~4啉g 楖礛`莾罀 s9匍韃笶 x奎3瀺 A 旇 g=HoQd咸QI 晎5闱鰑疬毮j+祑G;潇=搞逇砍劗[Y d<癅蟬窞2:y霪c催鴊 黜+賖 唜 9 ~覐鴊} 黜+賖 唚 ; ~覜 耄衯 {= 鹞7o 镖R9柽 縤^袳 x奎3瀺 A 9柽 縤^袳 x奎3瀺 A 晈J裏7c‥sw}{} l葈獛Gf郎 缞鹾(▔ k j獖 UQ :( ( ( ( ( ( ( (GZZA謻
(
(
(
(
(?贍F u`需5.仙昕 JFIF ` ` C
$.' ",# (7),01444 '9=82<.342 C 2! !22222222222222222222222222222222222222222222222222 :"
} !1AQa"q2亼#B绷R佯$3br
%&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz儎厗噲墛挀敃枟槞殺￥ウЖ┆渤吹斗腹郝媚牌侨墒矣哉肿刭卺忏溴骁栝犟蝮趱鲼 ) (
/ 0 0 D A r i a l n g s ü ü 0- ( 0 ( z[ 0 D 媅SO a l n g s ü ü 0- ( 0 ( z[ 0 D T a h o m a g s ü ü 0- ( 0 ( z[ 0 0 D W i n g d i n g s ü ü 0- ( 0 ( z[ 0
A .
@ n ? " d d @ @@ `` # n
! # $ ? 饎 R $ qN謅9襉燓p R $ 浪 藘:q豅韨 ; R $ yT%X{YxY赔pJ辪 y 统 0 咥 臕 @ 8
3 簱蚌 蕷;斍 蕷; g 4 [ d [ d @ z[ 0 揀 p p p @ < 4 d d d d l 0ü - 8 0 _ _ _ P P T 1 0
p p # Antiarrhythmic drugs
OVERVIEW the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k INTRODUCTION TO THE ARRHYTHMIAS cardiac arrhythmias may cause the heart
(1) to beat too slowly (sinus bradycardia);
(2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter);
(3) to respond to impulses originating from sites other than the SA node;
(4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). P P G ? * Causes of arrhythmias Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization
if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, , v ( Effect of drugs on automaticity Most of the antiarrhythmic agents suppress automaticity
(1) by decreasing the slope of Phase 4 (diastolic) depolarization
(2) by raising the threshold of discharge to a less negative voltage. , # Abnormalities in impulse conduction / Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. 0 Z 0 , Effects of drugs on conduction abnormalities Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. Antiarrhythmic drugs G the antiarrhythmic drugs can modify impulse generation and conduction. . 5
CLASS I ANTIARRHYTHMIC DRUGS $ Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels
Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. , A V
Use-dependence : Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence ; Z ; g
Quinidine Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0
. It also decreases the slope of Phase 4 spontaneous depolarization.
Actions Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity.
Quinidine also prevents reentry arrhythmias H
D % Therapeutic uses in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. t =
7
K Adverse effects A potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole.
At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. b $ A
Procainamide p 1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of Pharmacokinetics c Procainamide is absorbed following oral administration.
Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential.
NAPA is eliminated via the kidney d d 6 - g Adverse effects W procainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients.
Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias.
Central nervious system (CNS) side effects include depression, hallucination and psychosis.
X Z X Z G
P 3 N
Lidocaine Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels.
Class IB drugs are particularly useful in treating ventricular arrhythmias.
Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. Z $ H Actions Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential
lidocaine suppresses arrhythmias caused by abnormal automaticity.
abolishes ventricular reentry. H 5 + " Pharmacokinetics \ Lidocaine is given intravenously because of extensive first-pass transformation by the liver T Adverse effects Lidocaine has a fairly wide toxic-to-therapeutic ratio;
it shows little impairment of left ventricular function,
The CNS effects include drowsiness, slurred speech, confusion, and convulsions;
cardiac arrhythmias may also occur. Z CLASS II ANTIARRHYTHMIC DRUGS $ 3 The Class II agents include the beta-adrenergic antagonists.
These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.
Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 4 4 H { q + Propranolol reduces the incidence of sudden arrhythmic death after myocardial infarction
The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. E !
Z ` 枛 葺 洙 33 PP ` 1 3 ` 33 洙 33 ` Q_{ 熓 览 懐 礻 ` 333 f 膒 KN 膩 v稩 ` 枛 j@v 郓 峥 澄 腑H > ? " d d @ , ? n < d @ ` 7 ` 2 @ ` 7 ` ` 2 n ? " d d @ @@ `` P R @ ` ` p > > | 餿
0 (
0 鹇
0
< 鋲 "
餒 " 0 C
疒
0
餞 寣 d "
餒 " 0 C
鹇
0
< $惢 " U_
餒 " 0 C
疒
0
餞 敁 d " >&
餒 " 0 C
鹪
0
餘 樆 " P
餒 " 0 C
鹇
0
< 悰 " p
餒 " 0 C
瘙
0
C 饃 8灮 ? d ? " bUv
餒 " 0 C
痄
0
< 臁 # " `
餖 US鸔dkY憦蚹Hrh槝7h_
0
0 模 "
饎 8 US鸔dkY憦蚹Hr噀,g7h_
,{孨
,{ N
,{踁
,{擭
痨
0
6 缉 " ]}
餪 * 0 痤
0
6 犬 " ] }
餬 * 0 痤
0
6 湷 " ]T}
餬 * 0 養
0 s * 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . (谐% B l e n d s
*
"
4 鹄 (
4 鹞 餞 +
4 " + 餬 餬 P @
4 # " D w o 餳
4
s * " P P 饊
4
養 d " P @ 餬 餬 P
0
4 # " N y 餳
4
s * " P
饊
4
養 d " P
0 饅
4
< " a * 餳
4
s * " 黏
4
餱 ? d ? " + ) 痍
4
養 饹q ? # " ` p q
餖 US鸔dkY憦蚹Hrh槝7h_
鹪
4
0 湠q " `
q
餘 US鸔dkY憦蚹HroRh槝7h_
痧
4
6 " `p q
餯 * 0 痱
4
6 " `p q
餱 * " 0 痱
4
6 8玵 " ` q
餱 * " 0 養
4 s * 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . (谐% * 饞 * (
饃
c $ 祋 4 p q
餽
S 鸬q
4 `
q
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . n皛a& 0
饦 0 0 (
饃
c $ * 0
饃
c $ X
0
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . n0貅C 0
饦 @ 0 (
饃
c $ h鮭 0
q
饃
c $ 腮q
0 q
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . n& 0
饦 P 0 (
饃
c $ 0
饃
c $
0
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . o= 0
饦 ` 0 (
饃
c $ 0
饃
c $ $
0
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . op瘰 0
饦 p 0 (
饃
c $ 0
饃
c $ d
0
餒
0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . o嘘珙 0
饦 $ 0 (
$ 饃
$ c $ d( 0
饃
$ c $ $)
0
餒
$ 0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . p@S宝 0
饦 , 0 (
, 饃
, c $ X/ 0
饃
, c $ T
0
餒
, 0 師 藿h ? 秽 33 櫃 櫶 8 0 _ _ _ P P T 1 0 . p衃异 痨 | 饇 (
| 餌
|
C A 1 餚
| s * 師 藿h ? " ` 33 洙 33 8 0 _ _ _ P P T 1 0 . E伹`莴 $
饘 8 $ (
8 餽
8 S m 0
餽
8 S 鑝
0
餒
8 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 雬郳. $
饘 < $ (
< 餽
< S 0s 0
餽
< S 坲
0
餒
< 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 韤犲 g $
饘 @ $ (
@ 餽
@ S 衼 0
餽
@ S
0
餒
@ 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 顎鸢峔 痨 饇 (
餌
C A 2 g 餚
s * 師 藿h ? " ` 33 洙 33 8 0 _ _ _ P P T 1 0 . E伹郻x 痨 0 饇 (
餌
C A 3 餚
s * 師 藿h ? " ` 33 洙 33 8 0 _ _ _ P P T 1 0 . E伹 $
饘 D $ (
D 餽
D S 葐 0
餽
D S 爾
0
餒
D 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 顎p $
饘 H $ (
H 餽
H S 缾 0
餽
H S 攽
0
餒
H 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 飥h咼 $
饘 0 L $ (
L 餽
L S L 0
餽
L S
0
餒
L 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 飥犝嬁 $
饘 @ P $ (
P 餽
P S 0
餽
P S P
0
餒
P 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 饊00h $
饘 P T $ (
T 餽
T S 0
餽
T S 飙
0
餒
T 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 駙` $
饘 ` X $ (
X 餽
X S 0
餽
X S 湺
0
餒
X 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 駙狅rq $
饘 p \ $ (
\ 餽
\ S @ 0
餽
\ S
0
餒
\ 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 駙P $
饘 ` $ (
` 餽
` S x 0
餽
` S L
0
餒
` 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 騹阑 $
饘 d $ (
d 餽
d S 嫁 0
餽
d S |
0
餒
d 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 騹:諔 $
饘 h $ (
h 餽
h S 0
餽
h S 袖
0
餒
h 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 騹愵涸 $
饘 l $ (
l 餽
l S 痣 0
餽
l S 撵
0
餒
l 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 騹 $
饘 p $ (
p 餽
p S D 0
餽
p S
0
餒
p 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 髝@峕 $
饘 t $ (
t 餽
t S 0
餽
t S h
0
餒
t 0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . 髝@寗 $
饘 @ $ (
餽
S `婋 0
餽
S ,4
0
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . +吳p鰓R r 緾 馝 )H aJ 橪 袾 ) 8 Q AS W 1Y ][ 蚥 鵧 %g Qi }k ﹎ 誳 r -t Yv 厁 眤 @ yU 塢 _ 輡 ?
! A+ (
/ 叁 鄥燆鵒h珣 +'迟0 PC h p
Antiarrhythmic drugs P wei Blends h wei 27 Microsoft PowerPoint P @ 磊墕 @ P Gn@ 悋 .吳 G 6B g ! - - @ ! - - ' 33 - - @ ! 4 0 - - ' - 55 - - @ ! 4 I - - :: - - @ ! 4 J - - @@ - - @ ! 4 K - - GG - - @ ! 4 L - - MM - - @ ! 4 M - - UU - - @ ! 4 N - - \\ - - @ ! 4 O - - dd - - @ ! 4 P - - ll - - @ ! 4 Q - - tt - - @ ! 4 R - - }} - - @ ! 4 S - - 厖 - - @ ! 4 T - - 帋 - - @ ! 4 U - - 棗 - - @ ! 4 V - - 牋 - - @ ! 4 W - - è - - @ ! 4 X - - 鞍 - - @ ! 4 Y - - 父 - - @ ! 4 Z - - 靠 - - @ ! 4 [ - - 破 - - @ ! 4 \ - - 屯 - - @ ! 4 ] - - 佑 - - @ ! 4 ^ - - 谮 - - @ ! 4 _ - - 哌 - - @ ! 4 ` - - 沣 - - @ ! 4 a - - 梃 - - @ ! 4 b - - 祆 - - @ ! 4 c - - 镲 - - @ ! 4 d - - 蝌 - - @ ! 4 e - - 貂 - - @ ! 4 f - - - - @ ! 4 g - - - - @ ! 4 h - - - - @ ! 4 i - - - - @ ! 4 j - - - - @ ! 4 k - - - ' - - @ ! 4 . D- - - ' - - - @ ! 4 DU - - - - @ ! 4 DV - - % - - @ ! 4 DW - - 0 - - @ ! 4 DX - - 8 - - @ ! 4 DY - - 褹 - - @ ! 4 DZ - - 覫 - - @ ! 4 D[ - - 訯 - - @ ! 4 D\ - - 語 - - @ ! 4 D] - - 謆 - - @ ! 4 D^ - - 譲 - - @ ! 4 D_ - - 豷 - - @ ! 4 D` - - 趞 - - @ ! 4 Da - - 蹌 - - @ ! 4 Db - - 輰 - - @ ! 4 Dc - - 邤 - - @ ! 4 Dd - - 釡 - - @ ! 4 De - - 悭 - - @ ! 4 Df - - 瀣 - - @ ! 4 Dg - - 绱 - - @ ! 4 Dh - - 榛 - - @ ! 4 Di - - 肓 - - @ ! 4 Dj - - 烊 - - @ ! 4 Dk - - 钗 - - @ ! 4 Dl - - 鹪 - - @ ! 4 Dm - - 蛸 - - @ ! 4 Dn - - 艮 - - @ ! 4 Do - - 蹉 - - @ ! 4 Dp - - 麋 - - @ ! 4 Dq - - - - @ ! 4 Dr - - - - @ ! 4 Ds - - - - @ ! 4 Dt - - - - @ ! 4 Du - - - - @ ! 4 Dv - - - - @ ! 4 Dw - - - - @ ! 4 Dx - - - - @ ! 4 Dy - - - - @ ! 4 Dz - - - - @ ! 4 D{ - - - - @ ! 4 D| - - - ' A . = < ( 汉 北 Ё 湝 憫 唵 {{ pp dd YY NN CC 88 ,, 破 浇 吵 煙 敂 墘 ~~ ss gg \\ QQ FF :: // 行 热 靠 抖 ⅱ 枛 寣 亖 vv jj __ TT HH == 儋 乙 适 亮 父 い 櫃 帋 剟 xx mm aa VV KK 後 圹 栽 烫 妹 梃 沣 苘 照 挝 铑 殚 滗 揶 鬃 篌 镲 觋 骀 噜 鼢 趑 痧 祆 珑 貂 耨 眄 种 蝌 鲻 _\`abMNOPQ/0123 \W]X^HIJKL !"#$WRXYZCDE[G?RSTUV>?@AB MNOPQ/012345678BHIJKL !"#$%&'() CDEFG >?@AB
/0123456789:;<= !"#$%&'()*+,-.
' - - @ ! s
E - - ' - - - @ ! d" - - - - @ ! d% - - - - @ ! d+ - - """ - - @ ! d0 - - $$$ - - @ ! d6 - - &&& - - @ ! d= - - ((( - - @ ! dB - - *** - - @ ! dH - - ,,, - - @ ! dM - - ... - - @ ! dT - - 000 - - @ ! d\ - - 222 - - @ ! d` - - 444 - - @ ! dh - - 666 - - @ ! dn - - 888 - - @ ! ds - - ::: - - @ ! dz - - <<< - - @ ! d - - >>> - - @ ! d - - @@@ - - @ ! d - - BBB - - @ ! d - - DDD - - @ ! d - - FFF - - @ ! d - - HHH - - @ ! d - - JJJ - - @ ! d - - LLL - - @ ! d - - NNN - - @ ! d - - PPP - - @ ! d - - RRR - - @ ! d - - TTT - - @ ! d - - VVV - - @ ! d - - XXX - - @ ! d - - ZZZ - - @ ! d - - \\\ - - @ ! d - - ^^^ - - @ ! d - - ``` - - @ ! d - - bbb - - @ ! d - - ddd - - @ ! d - - fff - - @ ! d - - hhh - - @ ! d - - jjj - - @ ! d
- - lll - - @ ! d - - nnn - - @ ! d - - ppp - - @ ! d - - rrr - - @ ! d! - - ttt - - @ ! d( - - vvv - - @ ! d- - - xxx - - @ ! d3 - - zzz - - @ ! d: - - ||| - - @ ! d> - - ~~~ - - @ ! dE - - - - @ ! dI - - 倐 - - @ ! dP - - 剟 - - @ ! dT - - 唵 - - @ ! d\ - - 垐 - - @ ! d` - - 妸 - - @ ! dg - - 寣 - - @ ! dl - - 帋 - - @ ! dr - - 悙 - - @ ! dw - - 拻 - - @ ! d} - - 敂 - - @ ! d - - 枛 - - @ ! d - - 槝 - - @ ! d - - 殮 - - @ ! d - - 湝 - - @ ! d - - 灋 - - @ ! d - - 牋 - - @ ! d - - ⅱ - - @ ! d - - い - - @ ! d - - Ζ - - @ ! d - - è - - @ ! d - - - - @ ! d - - - - @ ! d - - - - @ ! d - - 鞍 - - @ ! d - - 膊 - - @ ! d - - 创 - - @ ! d - - 抖 - - @ ! d - - 父 - - @ ! d - - 汉 - - @ ! d - - 技 - - @ ! d - - 揪 - - @ ! d - - 览 - - @ ! d - - 侣 - - @ ! d - - 哪 - - @ ! d - - 破 - - @ ! d$ - - 热 - - @ ! d, - - 适 - - @ ! d3 - - 烫 - - @ ! d; - - 挝 - - @ ! dB - - 行 - - @ ! dJ - - 乙 - - @ ! dQ - - 栽 - - @ ! d\ - - 种 - - @ ! dd - - 刎 - - @ ! dk - - 谮 - - @ ! dv - - 苘 - - @ ! d~ - - 揶 - - @ ! d - - 噜 - - @ ! d - - 忖 - - @ ! d - - 滗 - - @ ! d - - 骀 - - @ ! d - - 梃 - - @ ! d - - 觋 - - @ ! d - - 祆 - - @ ! d - - 铑 - - @ ! d - - 痧 - - @ ! d - - 蝌 - - @ ! d - - 趑 - - @ ! d - - 鲻 - - @ ! d0 - - - - @ ! dF - - - - @ ! ! d` - - - - @ ! ) d - - - - @ ! . d - - - ' @ Tahoma - . 33 2
Ev Antiarrhythmic% " " # 3 . "System 桤 - @ Tahoma - . 33 2
E drugs " " " . -
! " # $ % & ' ( ) * + , . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c d e f g h i j k l m n o p q r s t u v w x y z { | } ~
w !1AQaq"2B憽绷 #3Rbr
$4%&'()*56789:CDEFGHIJSTUVWXYZcdefghijstuvwxyz們剠唶垑姃摂晼棙櫄ⅲぅΗī炒刀犯购旅呐魄壬室釉罩棕仝忏溴骁栝牝篝貊鼬 ? 髭(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
wjm; QE QE QE QE QE 6((((((汞鴸}+
2賜醐RS 豍B邃or@漯8蜧K\?洮|=?鶱(V呙#0黒0E反玾 "踼2I荢R =戌 - 畮 ? 鑤 屟 龇 CΝ 黤:( 剓[ ∮V 繹?3G#谶毞 駳梃s韔M[ l 饛k:j啉 g 苉＂9哮G悼 5o 4= 虚- 畮 ? 鑤 屟 龇 CΛ 稛黤:( 剓[ ∮V 繹?3G#哼悍 駳(k輘m[ l 饚k燈; g 苉ア81? y那2朢4;}r領蹆憣 x%馃弻蝏鴺c盻C穊`H#'閉臲鴚菛蜋紏ov7壌8# $嬊 ６A俘忋_磯.佣l垆 b顼{u堑uTP3龣/艨7 ｛3芲3&o?]5fx渠唥/ 氰恬忼 鷂 徸KE s_贋1 K 3聱?硘a C6 倂 沲已@ 做g鑖 餖唿~擕3芲3&o?]5 fx塔唥/ 氰恬楜 鷂 徸ME s?贋1 K 3聱_煜 邢 鄼盔齮碢5龣 纯 7艪iD0懒辂钎t訮 qu鉣
e缓]/Y余銴X炥鍡nIUgd=橙 糤Uiu鯗v 57^尙2鋔j 囡腒糇m-㎜扻J 2獦\B鐚儌9晌躻( ( ( ( ( ( ( ( ( )荸搭 QE QE QE QE QE (
(
(
(
(
(
<>*i簬彥iz瀴yr…桺嘸'h $ c兺q~乽O+]揧3,痟矋岗Qc w$過鮷鉄嫚/a]3_X谲聿跃豠與禃w/w(z8 *+5昕 o<7桺迎
$頡5*硶L7 駟9胪^脊6厢鈞掱蚁N礦箍伓\輆n,2s蕩兢漶@ 跡y 棬k鴺贾o5?Q睊孓k7M 顼rH悒# ?
淡WQ鳦+垌N蜿)瓺s;<F湆O孕盦_8雫${龚莭swp曹 89`0:鶺E饽馟脣臈>/驹m绾[}J 沈股&8囀誳p@#├瓣簩:F弡┸+v騖H# 盩R#
艧穫蠆R;鞑[5枣毨[麮t藻yщ杜!甥瓴跢F<`馹EExw#x锩鱓1;(o睩蚴= Q恠屽廫q儸|M 芦
E5mu d[M5观(墭 m9< 骨4魙 %拯Q疔7谖，6k31碙耳y撵\曵
./忺釈o]鴲jB/)痩$祶QC98$.@餁 "褶'&餼[斣釦釟1? 侼v滘 囿=5x牷婋鰩/X缬`b2y侵ヰ?壸Z荆c
>轊娹;T滀岦虐x酂]躢煸W蠚锬 Z"硗护k偮忸8c难暃 r@995襧椷竣( ( ( ( ( ( ( ( ( τ籔EPEPEPEPEPh ( ( ( ( ( +勸W鼤o囘]G D
铍勸W鼤o ]G D
铊 箫2 症嫨緯磞羠抈 !眮瀤莦圃刖.礸駉婱汪#e憘貲P侫r6$ v设=j玧鲒^漵╚I錤跠沂鸎mU' x 挍犰r|T否篲堏8=牱 X|稄q}迍鹫?9秸糘妡7c隥F#v1nI皃 纑C Wg㈦Z埓5]*沩S铗遑苫k<0r銾 鄚1痱暧^撃(瘴 @$K P鵃嫫y泔 ;瀢L鳨釳5-#J駰質=|\!梟9鑡羍#8狏
(鏮>葛熋 77﹔館藟b對甍b9'8,y惴逕 "约Gλ
J淥inb +暺1 O 鄙雽n5[ApO r96鉘w櫗 O腐,觺jV_ 鯊>譝鲖p搥零9z呭恙漥鱓譖踇7<rp2O毀廈债
緵璱讚,c逗I\)' 笏瘏Z岨!饐5Q 噆g菴fC 厜^;鐚抓j趌茟y]吗筍 {骔(#傍_恹
選e|]枰$$Ko滅?!'睿柫=0:溬壶[ㄜi 礭B7囦g槓貤2#|皕┭@ w腳'庺hm阴韁薿&2槐褔\{帩y閈轼i鉂KY5}{篷轢iw>h孻(E@A马+扟I 夔澡颈承$kxc侵碓宱璾+C'室.$寁#僎.絮}wK駵囤佩澟驮~F e<役癗A蓼酂搅5>!答瘲 邏m鬽伡告話,Fv唦炥乍aoema ZtV馳吿In
y鵅駜滖隌 U鹂>%偮夏谄憇筓掹+O糇vy剓觞Ny袭獎EQ
Z娾 Ky..f"R襅#T$ | 饹O瘠竞甬┃G 棴 斗棼T埿鶊藪蚾^簱峤m+a隣odV冂c U牢 +拙O|W╄ 牔淸毛Ν嬋X8 崯O善x〡 菑 嶞-.斠坓WY 悞( d 蚌蝯娿顋
泔ipx腪4x貺揨年焧6@ > q汐挹Aq ]C 珝熻&8咗}裰┅x譛效穲-瑲+涑3
斱 洖s料a蘨?|Y%睢<9a4A-"鵿 `翭 n浏, 仠譟狓[苝麰阶锃4壮崿 ,擅!(@e靪u琅bj駷眂╗k~瘀,ア誦憁 J Xw脋=o耦珄+ 崋惭C鏏猉'BTO
寣`9壬撫>健]xgW&抵o糌D6拽颤玟-3
q豽狱Ru送C]僋禹
旆俺蘣wc强(C茷 绸茲ma╙\胦鈣癿I鬰 k萴軬鉵乵Ｂ骚崓 g<醰帴渊 z﹟E衸E鲰釢Z{隮|.9%窼U橦樽氭<]/ 鑪讏t{]
祭c'{ .T 廄9鯛E%W咍}F)炓蔵戕2粦 廘婓O x掀毼媢!ik峄.(詏*瘑@T 靇9Ry=+闹3隇4鸴
耪屝Dd*2{rk濔弰n韣'叺潻;<攎酑汇
髈鳼.m?鴖 wr,曡~|鼷0}>'胱 ,疱噯lm.≈t院Xg萪懠纖8=fN;N:諩梺芯!|:嘝阳薟盀濡傞畺-剙粰I*L Nh穽|E >]陊朹f堪綡,S*丘葂9苢}c碰,tK傣-婧燥侐∧Y 恱酇檐sU. 鴤哙瞟
楘睿|/fH銾]庞 3m u2}髱諌w 翶猁腼女ie擂E崚 瑣搩塺躰`g 殖夆茞閣::浦鱒罉
&茔q#r1蕨徠>, ╧7:鯠襫槆3G茌'^ VQ餑奼兤c媘?鸙扯硽匤:鼰xa睊N $7L{;o
暄55Sι 兲O緎伝;{跷(濔fｂ鞸7嚸zr 詓F衿0WiP k9靓嶞G 錃薕疽t鯖蠟6_5昇艍橋X亴巼' V 鴭m鹈O鹞煢旙n'}B%箘筍菘?6@翮摺恤豿Vo
賦.逪禋謉7荙奊2樜 厄Y* t
Z煆!鑊 謚曅,*8笖7t 巗+烋 塽焾 "]:犯毅%賑叩)8by ┲黃傦t栶 ｊ 礗餇yj
莐u##9须~駁趞猧'讦徐鄪嬲嵎菍嵟眱帬灒 }柣2~效K接4:[ "m遜Vl9=3懹钫 莮5鴥}狾(t-*椭8汻G2J膚豀 2}2:酯仇噳 沌%撻^N$+篛碏臁
6銍任;g瘅嘃w鹩R宅?霘5枣XK糕1觪$s儍荱惹puo寊寨佹簬谖 i盈溓船2侫1憣珏< 娮获弿鬗_B焁4呉禌拳櫶志aW'` 2Ё屉 黃/偗蕣楓p2 Iz畚镹y=F:}'呛キ3裏m鐌媂傛沌U鐂rFq2h储竃|a璆駟 5崻閞贈暉鎖Yv煕 酕餡v肴
(*j燆 牃'徇鼣M縞蹙 iW姞抈p 矧汏 徇鼣]縞Q@Q@Q@Q@Q@Q@Q@Q@Q@;6澸
(
(
(
(
(EPEPEPEPEPEP\/洫x毹鑱]誴) 挬 wTQE P婨 謌"眮5蠫-萇澰c倉>U鼌_;觺&K'妡O篳楚枚氾z1(腮癅戡娌->4<u?M,W杦Q@柧cmp酘b劂嶇隌 祽渄g覗紐鱑崀5iI/喲麯赮昫鹝(Y<晭Ww{绲s 拯IqC娿L& 吜 ]嗒(衔 er緳d~數螫x婦蜷 :厧,w抅,Hq $ 濭 岤 僉蛹
る裏K5娆蛋
抅X,aI羯揉sH⒓倬"脍[肞iVZ將粠$哈痨芅p98-菕 5 5奊 擻 /們c徔脍;z+弱蠄:境@觮6m}瑨掳蔡 nGU兇 滬s^ T金D+{hV=遝籭兊芼搤GU贎 鯛H d/j 阀h嚗寨扰溑k rp軭ótY聑茢,5 -2y芓.,窘鷆Y恟+&忝:=讐瓅G5烅Z# 7 k崍C6兇;+缲5
Z做y賑l^扬\\ 5FS 辗G +荡鵁醎嚲 MGCi礫福嘜稁9竸E 贅寪X$鎬=帄蟓#釴$駄 5憧康捙LV秇Y/蹌8只|H嬇z垫峺h獃璳s湗y
A鶉t 倇 w4靛 鸸缂僐源達hzy犛垎8
T鋵 搨 5黒阳+I复霸u 較 :势縳汆<銗G烁鸓犙\.忨SE詃詍镬=颩雏e嵖柭1寱$蛩@'p5蜟褛_I=^?<唱
! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c d e f g h i j k l m n o p q r s t u v w x y z { | } ~
! " # $ % & ' ( ) * + , - . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c e f g h i j k l m n o p q r s t u v w x y z { | } ~ R o o t E n t r y 崄d汷嗞 ) 碀 .吳 P i c t u r e s 6 C u r r e n t U s e r ) S u m m a r y I n f o r m a t i o n ( C P o w e r P o i n t D o c u m e n t ( d 礜 D o c u m e n t S u m m a r y I n f o r m a t i o n 8 0 0 D A r i a l n g s 埞 埞 0- 鸱 0 z[ 0 D 媅SO a l n g s 埞 埞 0- 鸱 0 z[ 0 D T a h o m a g s 埞 埞 0- 鸱 0 z[ 0 0 D W i n g d i n g s 埞 埞 0- 鸱 0 z[ 0
A .
@ n ? " d d @ @@ `` # n
! # $ ? 饎 R $ qN謅9襉燓p R $ 浪 藘:q豅韨 ; R $ yT%X{YxY赔pJ辪 y 统 0 咥 臕 @ 8
3 簱蚌 蕷;斍 蕷; g 4 [ d [ d z[ 0 揀 p p p @ < 4 d d d d L 0埞 - 8 0 _ _ _ P P T 1 0
p p p% Antiarrhythmic drugs
OVERVIEW the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k INTRODUCTION TO THE ARRHYTHMIAS cardiac arrhythmias may cause the heart
(1) to beat too slowly (sinus bradycardia);
(2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter);
(3) to respond to impulses originating from sites other than the SA node;
(4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). P P G ? * Causes of arrhythmias Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization
if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, , v ( Effect of drugs on automaticity Most of the antiarrhythmic agents suppress automaticity
(1) by decreasing the slope of Phase 4 (diastolic) depolarization
(2) by raising the threshold of discharge to a less negative voltage. , # Abnormalities in impulse conduction / Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. 0 Z 0 , Effects of drugs on conduction abnormalities Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. Antiarrhythmic drugs G the antiarrhythmic drugs can modify impulse generation and conduction. . 5
CLASS I ANTIARRHYTHMIC DRUGS $ Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels
Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. , A V
Use-dependence : Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence ; Z ; g
Quinidine Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0
. It also decreases the slope of Phase 4 spontaneous depolarization.
Actions Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity.
Quinidine also prevents reentry arrhythmias H
D % Therapeutic uses in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. t =
7
K Adverse effects A potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole.
At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. b $ A
Procainamide p 1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of Pharmacokinetics c Procainamide is absorbed following oral administration.
Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential.
NAPA is eliminated via the kidney d d 6 - g Adverse effects W procainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients.
Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias.
Central nervious system (CNS) side effects include depression, hallucination and psychosis.
X Z X Z G
P 3 N
Lidocaine Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels.
Class IB drugs are particularly useful in treating ventricular arrhythmias.
Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. Z $ H Actions Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential
lidocaine suppresses arrhythmias caused by abnormal automaticity.
abolishes ventricular reentry. H 5 + " Pharmacokinetics \ Lidocaine is given intravenously because of extensive first-pass transformation by the liver T Adverse effects Lidocaine has a fairly wide toxic-to-therapeutic ratio;
it shows little impairment of left ventricular function,
The CNS effects include drowsiness, slurred speech, confusion, and convulsions;
cardiac arrhythmias may also occur. Z CLASS II ANTIARRHYTHMIC DRUGS $ 3 The Class II agents include the beta-adrenergic antagonists.
These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.
Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 4 4 H { q + Propranolol reduces the incidence of sudden arrhythmic death after myocardial infarction
The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. E ! CLASS III ANTIARRHYTHMIC DRUGS 5 Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells.
prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential.
Instead, they prolong the effective refractory period. 6 6 0 a 7 $
饘 @ $ (
餽
S `婋 0
餽
S ,4
0
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . +吳p鰓R r ! ?
2 ! + (
/ 0 0 D A r i a l n g s 埞 埞 0- 鸱 0
胀諟.摋 +,0
在屏幕上显示 e jd 礜 [ $ A ) Arial 宋体 Tahoma
Wingdings Blends Antiarrhythmic drugs
OVERVIEW ! INTRODUCTION TO THE ARRHYTHMIAS Causes of arrhythmias Effect of drugs on automaticity $ Abnormalities in impulse conduction - Effects of drugs on conduction abnormalities Antiarrhythmic drugs 幻灯片 9 CLASS I ANTIARRHYTHMIC DRUGS Use-dependence Quinidine
幻灯片 13
幻灯片 14 Mechanism of action Actions Therapeutic uses Adverse effects Procainamide Pharmacokinetics Adverse effects Lidocaine Actions Pharmacokinetics Adverse effects CLASS II ANTIARRHYTHMIC DRUGS Propranolol CLASS III ANTIARRHYTHMIC DRUGS
幻灯片 29
幻灯片 30 CLASS IV ANTIARRHYTHMIC DRUGS Verapamil and diltiazem Actions Therapeuti _缿銘N wei w e i c uses Pharmacokinetics Adverse effects 已用的字体 演示文稿设计模板 幻灯片标题 $ m石a茜 嶚鸀(#4鑥i礹臁]Bh腞\ c >=Eks
恧7V 57 H?懐
饡委駅霓%>)拄 2〆oc9噅>锣 >n錈 铘W饗臍焿|d75鯐速#;鞺l剥魍凈醍騹
狩鼣 坑5 )'鬆( ( ( ( ( ( ( ( ( )荸搭 QE QE QE QE QE (
(
(
(
(
(
醸U %W 譖 华醸U %W 譗 ;(<馇厊L啠巅 蒩宅
侗捊
:蓛觧7` gmZ 璏&跦巢sY^\劝晢?"7B噦紖?.<饨聤 騧CH赃鰪业D盈NK6W1塐(羭` :嶀鹠cG駉膋 觏 各/kw 4?(潡-渔 苰里^錏 x飥鬩V相.咖]i棸_K鑾赬er補@R2rx s\脁腟0饉ネ⑤田a<$uiA晾*8 1涎4P妜|WM#F嚶z瀷m鈃^輏1靀~@跭鄐缨Q 傍嬃鯈}|3簙 '眿锑鵪$pwc蜴骄 疬
h#捽鉀哞7枟荡n鞊 妔升陰2:笈ue椒餞z.。jZ}茷蜅挤h抋#
匁荂閼隵婨 x纺扁楕媊穳e鹄丏,珂轁減+潞脓嫾[.熱McI耶)獠嗘轛%姟 哥鎙$兦j
餥
雿:j:W鯡蜿-w-＠+(悇d錞低Y执k 嵬c诵R 胾&绖qC觩鐷
*宜X駖WV &谳豹隬
瘏X鋐2q垳怠#J詔捋陃VS6ゎ避卵盻.!寖媳疨P藶 皈堗鴈+It
V;泬,L0綔佷#诟衫#8閊囥T圾猃>跰紴(l剸袬"
#冮^罞 x鲝碝gHｘ譔杨祂8 <椽2煍沊讗s
cZx巓褈 篃I挂 9!= n<櫉,坷N渀鳢M駑乥馝斩N籧勾攢W9.y贻1诇*/xt茗婽疹u漗X)q:腍U^9 =N@(|k 抂 譎鬸谉k 2揦鴄呙诜鐾諐⒛<燫H搆 儢G瀫r~Z鯫xf?鴉鏓栭瓛vF2猲#k閼閃鬽9t} O抑C*氽Gn$#(\愣q@ 3a>濢@xv聅=4嶓e栞唕GSG-湛猢鞝螽Ｒ肆 ;媥Jp+郇柨稺膥钟臵鐖n豸yLL* Cy帯6匳蹾壤N 璠<4餌幊 ,p雤{醡賓m菺<銓鄪鶥丂 5Zx嚸 桩麿〉姛碸蒲lu`锠审o;
溷 佛肢w夤5?磢朷
&蛐涉钹2wbwn ;子擯
4 槎QE$Q圳+ 堦F9 餹 馩4絯鞶せ%訕峦鰯C&褠1 q!癄┋I穤+m;#8> _ : (((((((((澸汵鞞Q@Q@Q@Q@Q@
( ( ( ( ( ( +侵梀穁 婌粭C濭気 %M拹8 籞(/F&嬧 s>摡踋\F鉹g8堙曃P:V桇蟒u鏌~耑殃ZC[踛QFU褩j 鋎帉2茑 闰沭G茋m?%h橥辇妩柁熯_尉`o佫5'= %i筐m >酤蟒toO/鏮/弫6 螂i +K
?瓶箅i +@ O颫/鏔酤蟒u!鉢黔璙囙穾鎼囈bc;せ垉眚4鮂酤toO锆鏮)宛W菓蘍tx銺黫w胬狃_莮w楜 蒇|系梅 縶83@ T颫/鏔酤蟒u蚧疋;(pn崃pi筐Ъ{ @ 鼫 嫚楏y:鵖飶 搻駎聺耧 A 判調欲所呀?究潀x ? L?紐G鼆?騬.>熯_螎辇妩脘佯c青琨 ' 怅E7汔s齺 搻駎鮲酤蟒to_尉S?|z 2.嗻;誙2B(7恜3熢 z}:u|
g沁 W嘛墸n餭
%|竳|N 燑 ( 匽;n餭 ㄨ瘲G 墸.餭 卌7鱛1 嶱4凋琰+ 壙 翆_黵￣渗k糕艶& h飍=>m厫: n:P贼Wh |W巅炊駯4<d6 牢 68<蹁c輙軯蟈觤 >u炓"鬬P{y傽á ( ]-帥ux虋癇驏sA9'訆#衢夏] G/孼黯'盟匾M酬ZF$嘂 喞>饧36燒ｑ3GB矘醱澸1鱲!e'啵袂z (((((((((澸汵鞞Q@Q@Q@Q@Q@
( ( ( ( Z ( J)h4 擰E QE QE
( 磾磾 RR袬 E.(ア ( ( (ぅ(((n-炡钷+ 噴Ty僜/,狃從MW胿ㄛ.﹌X$
睤 狘Ж 颺乗M琰枬3罁枵趭(+茷%徛^菊鬯2臎`嶤膾c╃搸佬嘃t,z菉 秧e嶍襞+##g367O =庎k鰘棯x哢鋺gOfs 爚点Q舥j牬鳁 8蓎 交択 hQxk:~鶍kB鸅飊 2I?廠謤5á ( ( ( ( ( ( ( ( )荸搭 QE QE QE QE QE (
(
(
(
ZJZ ( ( J(拃
(
QIJ( ぇR J(
(
(
(
JZ()h
(
(
(
醫噈c忸箌贓擹r1#1堛 徍G=弞雞岼 F皆Z买禣\ 汴zW;疸H烴鸩捱3>カ授嵺:!淞踿8 c幥=: 緤(緉怍贮C 噂#M1楲s蚣 /譿扎髂/<),昂 h]f U輪 G/廍膈里_1hz 鲓5鹽*全轢姑J 棠 Os4阓#%证'篎[{\舓扊睟0汪Pq訏輝"晋硘?≮xoA骋,[G障Vc領'癍* ( ( ( ( ( ( ( ( ( )荸搭 QE QE QE QE QE (
(
(
(
(
\襋@ IE R襌Aイ4 覧 R袸 Z
&h((((((((*Η㈱楮e危{(娳3$孫a貃瀫w&9 塽@皆豷遨#觏侅9#慮气L畸-鐗5dQ猭r 缡蕥 "* *+洏l韋焊怗(d戂ⅷ'颟k摸5暉職d臢繎 FD]:`俻}紼 y悄 I 蟴ブ?葳奈HT n疗 撉p9苉筑 !喘7[蠩蒸[m? 鋫:$m#旨厢w侽瘂*踚鲰 -%c扎*寬N y)崛|1毺29烆轶衡frO'隌tQT鮙R覧耶u+<籯t/#c媗zW輷8疧
鴽N6爝21 v )7i ( τ M )鐴 歷)盖9
@4i4犫敍 臹#娥穯ou嫆
钚 薎
繅#2{P瑋QZ眍媑‥63q
凃t渀鄲 885瘖m#囗]竑}CO7殧寚s% 额V ,籫廌5=+N烶靖H- M騄莯?u
!帧痤噑┩J!lJ虱#匬I$燄鳲铭刉w #.粄瘱6YD9＄%8'/襱鵸鼺 j型沘6?言鋣a儍潃惝k x蚯:V髹62煶[g髗(齴d耧彫<ワ}酬3鬹]-觶(齴o榦 S圯<窔呌甂 乁G 缘
W:骪芗穤呠乁TI'Tzv W A帻 .n
璡7Ho( |#8 q姪鹣釋>乽MQmnE荘薼T x幁2OQKI@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@;6澸
(
(
(
(
(EP馹W誰t=/M酗E灒琷P厍1(瓬惱 柬鐡俼L悍壶uqぼE玧z帍ut秝盻 Z&悁挮d!簈V>*鑪灜醁/tE擢梓戧6缺噄 y十{蠡 鏷婀 x荊瘭嚑i 勤;鼺轈g-%海啇:燶u=z2@X^7fO 鴯諍查w$pA驓姬L咀=餡M駦繅/鐠姿g肮Df蚣柬8#澢 {腨鴵暮^厂Xx端KD榨x L朏18]%m2撊 c殽鹱R-xWW繗螂L俭-骞敿弌'+射亐z渘钎 z (|M 蠋.5 铜捾蟨% # 睍苧T钗kz
ZJ(sE6杸 9ó攷颟壚瓔)忼3o錊 (宵$+ 鏌.颭O臬Y!_搼@2仛Y$i H<礩琏趒@<拈巌1讷锪ミ(t;F纞^辗￡ 伧比蠄髺甹IV* >gr9犮 溭z輽觓甇V鴯,簔n邱1^X{IQ訐@t 牝倊讖m 4諹w-祥\闑絨NT驇覢 艔;竝nc驩畄]N濄:;鱈{c5鋔>酧P蜄S( 康粿刑崯~j览蝛另5 厘$籑菕堑5鵒艻4鑐俴冎f )鴳v5f毖v闣瞰戠身钥|彙#扭鷗桻L*
N鳭.鉠妢U捏顁蹘0:衾鞞 占Wv砕蝸釞7R2
憘?*銃;醈bSj|Wx梡镹c訝^b﹒7't匑*2v'' +宁)尹#CV扝鄆K迤\98悃 瀜襽6胛1箛4 J綱煩历f8A礝 屇惣;c8 W┲^会'闹荵矌蛸drFA#駹k釢耻i&箤縱?.皟$'( z粃娭+8--k hv獙
ク[j穤-:%黇滠K慣
烶1瀜溾4璁 繇傠满.甂|荕0q儚趺彪醍饴[媿>趉籣曹级)損岚r2:鈥'J颸襩/误S卜筪r櫰 3苆4 v
羯繒X蟴4霌忶b 蕗> ~虍踺n<7p 譂倇m焖恍弥#莰蓋 坧皙 賎猫=荤邸蚗皹悏&>a掃韟}h@+z殥<聧逬瓄}g =訯?鱅翣3<*3u奋烏桗暎7
3廝x㏑%箮?g<&硳=(佁y\f h."44 a}h賐x 德雤 塼 6=鋏K[ 讚]鬏撯9枰#髺9乖礓 ↖Hそ-鰦R-#./z氀逢z拋'5fm>+召>砜於( 缱%ykf嚝瞔#f譈刀羕夳扯狷姚寲蟥傛L) 薞棓蛼(,卌! 瑇翳Mz++r>^?叁繒唤Vky!b褸G5-,wD焯_ n=:{蓔{#
YU窦&鈝 A娤沕挂f穏* `咟朐j埳#+▲忦暧臵s輀F珃嫈> 恸n梗问6蕏洴錥B .h捥(劘U ; 忈咄τu ,けE_觰涰9$涀压PH鸺孴 焰箾/ jC瀚n2:玷晅矇Y!驑( 62间t?雨( 匫2審z怗嶨Jr7n h D=陁坆昑炘龓# 塖sb琺弉 "!蝚羂&p
鲳創z3[~%嵗恉sU"L妏]崄蝖4勰即I巋币t,萾>钟颓欥xV=33轧u蔫捍簘蠦IG历W{e8j鹮梮1矄岎E|笋K料釢{碇焰妈8緃倣 膶寊 WG栴垃3繖m镏把齑E鵫拄埯mJ魐8'毚汛r紝s^Ag=譄/趍疂 又/:春潗i質哑蝖qI莸4=k3W,磇!{ .-$渧玓x疌緌鋔P滗狎噷g>笺4┒_|訨~A姇 訍:姃4 芤# 絁爢
o鑪谯潭#樫s鎞:觞U転舯A瞘u錣Tt粝い NE9A驾厸.:}+l渳畲 濋聯銺 ZJ)h ( ( ( ( ( ( ( ( ( ( ( ( τ籔EPEPEPEPEPh ( ( +'P鹌嚜坳^闁&梮M0S曑 r;W/鸱S驹ⅠH炯炵禚016酕zj铷蝩O剉1鴽^ 傓+嫙6躲h1荓 *~x鲡I糫"鉓+ C"xC拋I薽'#R}﹋簛音閛曊饽7 犊趾K[Xl炊孏琿9讵0+旞橕< ! |毗鈿32駨C1?み均k/H 笖Igl+ N 楣敁郑l鞘醌>e;絡俼@ 躾 '镹n(锧 呙e危+汵+詯鉼y$ O P踫娎駠嗧麿燶Y炭;.T銗EtsKM |_wi6壃Mη崍#鵗濬Nw zWn饊2GX:O磜'婒{y|柙
#F囧=+CK織N簫$(<憬W騿y"@BxX襫庠碚膝-邌t珕
-攎(}狎C)蝬9如潸氞|=┒梴慈|=螶酐k吀乨9 舜 \W7&忊{{殓爸`吖芳尠U楞x绨 笊<揮r﹃8 s柜骪女X跜 |E4崛$ 凒m謿M剹子m* B 艸Q榆姵 )U")dP5棅4ME眎猌蔄罳
羚阫~&2{?肸凥掗全尤O(徟q[簎叾洤Cei"(>z蜟m0檦甬参醥-阵现记Z雕_谝鉈挥Z咚伥棻谤碀嶙滝拎{諒
k*媃幱U痍Ch霮夼~尐6鋦焫漶P(坤颩〡q湡J痠g+=曑( 腥 鑠h((镋 6奡I@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@;6澸
(
(
(
(
(EPEPEP囪~#火梹~!k1A-童&負侾顠$9 冄弞舡7芕鱚
纷瞽f厡塷ql竑奵(墬z鷖幷涶gJ乖~隫Ze敁軱a+
糴澣2N'O醁 2K莌荦嘳炂9yWqH嵒o鹮?鐞蟐@=^婒璯T苑x烼杨糃=茮3%篩#]虨[>X`浒] >)炓X 螉#4叚x7N盏礨e赣ux埮龐鋚1蛉+"佑5攟U瑇M!嬈6b[#r鋷FN;zB 4 靛淀猐Z苊=划鋿' =A K馶 餔捗*噹H2簯怉 Gz鬅関~唌s梅w:ky籑gp纃枍p# * 儗 醥扬茀碛頫9哳9o窸z鬨z@衇雵鴿'黃R☆7~Y9TI#ux軨+)萡z}+侙氝,u=<噊鏎 M 仄毛 征(瓝麟?@鏕秐檶sWW搉郞 5馨溤蟞沔
$@H<鄟 a Q獎绉z潰#w閁 I扇=h隐晵+嘠呥+袚5气2;堛h櫚N{ k蕕P吁朴S4P躃籦]* c芛Hu'g鬬8隒 +嵮糘/木 檂 @胜? =惩v!M P誸傅->{Y:J刴#<銉_%kL駏顩4m鍑!?Jv
x锲
%談:栠B鋼@ >bw8椰^嘤ln拍!斾 $)Z<'瓨 祺
?w5蘂鱭趫$嗜pT禓4{应*HI.Er謻u9 W_ x; v辤 *M村_楶鵼1R聘 r嫗曾緊殞g幵鋆瘉襽6豉兝c 刅锫^虠0#O篖ys轵祷!9N茺?惈餔c恠舤6 ア镼鑪jX舥yr埬/&2缮7 qU|Mw釱;8'疰沢ㄈ拑=大槤汩堐顔9c5皔9
釗璷q瘈|E菳畛.裑89e#
3赘(ゝP啦 )k徴h锭q+6:茨e}$r8壬#觼狼o胇源 ㎝蠆u-Z小H牻
虦 p2 dKI毾護o繇怙L役S紝 ⑻9鶑'瓻-钖;伐膪"1菣╥为88鍂u 哐U/m-:邺襉2陉%贔鋊
FA j QE QE QE QE QE QE QE QE 钤趙j ( ( ( ( ( mQ@Q@Q@E=到*\A 痊 , =臟E s偞 ]畾庖Dk7;飘H奇E!Y截吏礽l秜PZＨ kis0'广璏E QE -cj5 跉=曐?W/ {ㄣ薅E oxv勖6_裒77Oda濷0B?氦嵺}&?夘慱鷘擔注 絕]駄o.(楙04炎宛憩m心H6輎z馂朔9珰Z-崩娀 ;4%汁硺 算5oM簓$3O 擩怶痾_櫸靦雳蕟?)鞞瞳X.枪@5+0.G~釜抙殀蘚@镎衝,.M沤嵒8贠 酅 醜羦釫
﨏 +g儨v v閾赠O胈 赦O傏蛡けjj瞉X:潓摛Q 灆9 Bzu W5E鰉芀(@M i;,V矸膡X潋u++%鑦[3/鏎 I肧 #叕53*摵']3侴□舘x{:澫聇駇煁酩謻 n$ 籪C湆.{鷰+垦t[熄\谽k陸橆鈷S塗 s撢竅飭囲$鸭-怡F崺J耓im脃q垜s柪 .y銹??&> 爸$UK桽 (繷岜靭廱+gU樱詔d 旂躡颤 岖o鴁螮磿C3淌% }p: 2q[l &穮黋{μ#,D^阒畒*悊5鑏 <4mz薌堐 瀔蝜燀簔J 8" 镼.D5ic毓隡x聙oL濎鎅T疷5H铩] 荍, >轫].涑簫Q攅;廢顯 `Q踳ps殰| 烂谣S>Q跉H鞞僋 :│LP 殯I紉鮅銙嗉sl蜚笼戻蹉& 8s,頣喃 谞B^攚:e幺m朙z 铘 ,jDz)<歶x穾眙[蠌Z 繄舆I鶎蝙k粅踾l 厍5/x娥鐗~擐jwkg&-喙)_鯌6馐 千甏f蓟狩腒Il祱糘;(!甄嗇.'駺] dd跋鳺ε,s聯C" U佷GQ@QE W/鈅
:外_閊*4{笐V4埇柲喩/ 侴_N概uP)犴7浦偖汞橼栂蓹郭O蕍彟:~u陨 '憙E,Bヽ佽$
u沦|^饈蕾{{>晅甊K]F葩6 A
羂褙渨舥鷙k歧L康絸1C-此"$eI鋛颮]Y谶@衇跜q ￢巇 腡zv暓h銎跮暗瞼眘+8酅鄐鞞璎/i蕤-帇7绚劚b-u8釙堥乡X|I苍〉績@袁<腇絽鋫_, 3 9诩苃发( ( ( ( ( τ籔EPEPEPEPEPh ( ( ( ( ))h S矷I迉y#I炁z 纸l )i w B蒁Zd1憸 釚'=狂韮Dc N {6轄髶妼┫ )&o诡j^`\兞蘹'u Z悞癄^鴡<:炰 液y醾h楴。;篧 F
皮#kW淔N7mB叵l饧驧政#梁苇u-曓埿\B龀 呬P/*s窞Q桂G5f婲禮OA擖6O陽:坥盥H \O胈棹
鴀i>猏_螇淝间`溩 |%━毂kv辛g:$褲磽蛋{8
k癞拕薸gs鬬涔 JЖ|A;"_L繂>l$!莑住0t`
矞pk/^矠鸐掁誧3?藱F@ 鉆 >!>!xR嫣磌u$EL,~elzW蟅16摥^iNYLNT苕線鹣聸-醯箿^硁m嶒擁韃]駕A民| 坋旗鱪柀場灩4Ds螶YcYT(癬+渇Lr:S鏇巟舐:蠚轉8蛌 B;讙閽档虏渟^廲|.橙嘈鎫h邅殎Υ) ;3Q<昡f琅5淙 D7Zk7栛扇獮f[ ) S嵐 uZ&阿E囁DV<1揮Ns券+奲:鐘鬽 鵲呆楕眰(勛-wp氧I籁貉b姨SK*+$踏檣wN饑嗶嬚接-:珠A 46戡20p@銑匐@*3зO甀!戭5粯&.#跓#z躿毱吁8xa5嫿t5叛秴4V鈃捜轵鞺 +-t &喥 H鐅扱m媠傲c 1犁竾饂咃t?
i阚]枳/{k鰇敀{f29;伾*攘鐏摓z嶑E音 66W2\[k2磯+猳C#岣亮权/鉥kP^]
_K梄窌趏 蚮`橴r
$尷溷9!癏绳拊<赓礛Uo锚]i尤 筒冖＃+1+岏灵也u_x炪N副拯3姜[E!曞Z鐕顋=-/膥%:滝s栝m╥sL痝r姟錭 齬r8 魺嬉醑闦迵琸毮)f枍{}
$D钸TbFNF3讘@ 嵓l|"t玨}*]KP.>蟢时)l侒9>痦幑"芖:'4 =F氋^'巔фTu昀腸8生殛氬厲乏h哟戇闗(硱E筓憆荇 漼詚V埂|Z絮/阫蕪eマ铃N蔔$墋A慉嘊q转厼乏jv稐笆l6踄渝Kit.9-莞G<俒飖棹M 瓸蹬 |扁mS襼栝ㄘ蟞駄螅よQ乪署z儽 q^凂谄+O厇4v & :rZ鯳9條保畇G]衪i2i毜贖A(I袀9躊憒M糼/喚氌闤/<鹢-旍~囕G鈣MO}獐 x団ａ陽簎灋綾y堕 e3笗'杔pF霁w穿4鹝[=U_矻裁銮鴷l 粚濷示噔_i锏_轞哧虂/鬹 鵘菳鸆(|q埒#谓-k@4榣經m瘣@a?u攕寴.xxk^
瀌\蚳 岁{b剥 汐茳_駥喉簨[[`侘b缮鄯'5侗轟Io 蔋籜{P>浳彬荥j0(;稸 稉棉5接i$%GO敀Et眅L 珔咸p)L{p{U牐vXc馥t鹰 0頥Ps藓
宰6ヽ斊p3迉=迦 M+>隰\ZFA鋚jM畚hs&M!揚 哨,<櫎幍YS瀮;<5栗蛅詷^c鱛舢>[晛TH惹
7鵖斓 "ωc9* O羢~敕趨枟m%妗y 闯HG鈑#X糟襹!=籑葜m瑽囏_,7H狌zパ3菱]N邝] UK5粫$yNJ祔苘 . 韂?叴[:轐齎a>眤頙佸 噃' 湌蘺4 僽輍n駑墽3,4恗 馏$詫s醍汛刿iz}禂$浈糀> j鲫J Z(( /xOL駇澕 赼=脚紴\叭:n啐a
戏 CX5-K]挣i4窿鞈斩曓B"頻 寄滣 琰s牊'W研皷錪2) 饃, l诪赦_佴 >芀栓-ab2 )69露q術祘f閆 >%檺.n鍖懙de婑濲滗濱鶳業.O 鲇_见>峩∨錈S瀞亷I魻奦;W 銅巐 - 杽崆酫釕率蛂佘$恗+@慲埼鑠U綪?pf2#I&尻衏 ~4蒭9琅!o輰u0e攪dp虨a?w╃#焣〦n簛B>陚F3 梅"^蓂鉏碥錠L&{+)竻堲駧)駝棊?vI流鈥*骗#v鏄 X侳{RX;罄 冞凊润N點)+s稛仦h憉砷Z耕T 馗E2鋠鞼l掹佞Hｕs幼l袳Z-F8嚑╄E丄1@Z\q@&)j禥jZe亭)"`咨簗S豿炴蛪F1豥鬃V ⒕_鴹h魔l亲aX#>77SQ汤
a昛0萃F z4CS訿裔梭H遰0p[%菈奠 x璬i詍dC澑8鍘NI
y趝垌N釬 懕q2 躎?a觢槏6{绹桰蕫xn掬 '/DS
轸=@O"H 6阝騱嗶= 鳤x#囯@ k熔媤5楰e#煞風c苃F 鉀q%帩w*咾x隧-穛3頿?痲 蚯比瑥}猰6
)&杭牟"Jx,O@X梭 -邙吨奩糱M@F2dqp:滅 椳f坜s
`Ca@c +;@馥緩d..u[搖!;e11觪-荀,誳迃 类廇0$珂B痬痦黯唶m3 萈n-萷q豔▅6<6kvo漒m 貭顏J9&毥h鎾滻@袱((((((((澸汵鞞Q@Q@Q@Q@Q@
('_?穕６铱于9D|啡` 9殪+塔!Z隫&佱MSX]R隬誕b 訠謥J*酺蛸bw=浅V?夵1籈揓誦g厧魌m@t=榙鷰pA蒙歐峾% .代;!騕韒 塦Q_ \罾'<沬ド;|;竟犊援.汑4Y嵈.s貑P1,=
鬕Oj鱅沇駈ォCト%穮鈲7H形早灲sKOa^驺瀹 怄5 ^醩" T4酼sy1緕妔藨娝溢-l!齙璍鶊ㄡ矦 $)湔$s蛤i^C潍趢,4窼QGpc:煒Py廊jH銹I=(协o 栺洗:掺 i掰bg叀]粗
1扮=玀鱫'w.
铞-票< X"h0< '$d銣 灲*掇2z誽侂 ^D嬈 龚D粶惞鶸 5` 珳鈥%i~Q廞]噣5k 2#茏 o诬诖鬹潥嵓睗)o蝷> 3N PZ纬贕*魆慥;PIK( ぅ((((((((澸汵鞞Q@Q@Q@Q@Q@
(i(袺F( 琀<)x歧1G"陊6⒅c尃┪耷銺钎m褗 宕?^xj啄,嫧熄尴 Q▓捜1 蘰W;馮|#酜竳[鴂W嬱2Y蚼:硑~阷x`x5塾W侷%鬻媜|1酠F6xN鈑滵货h沞憨^ RH=姰wH痻 闹&= B,蝹S鲃j 90'j:嗻4瘤h荌T澨>唨=OW馞櫍DZ鎢啐9+ 胫{{騝s閵鱗 噡戒i癇}c@
f[|5灿`筟e/8秋[咜P勍$‵ 伹Z志撿(悍騽{B癡蝪01?Oz膈?吘)栬群擲A滌憳銮N櫯Om KR甄瀤E煑`pF;Pj亦$y'ZW儻,屍嶗夈婏豬懇u骪wnkTP`聙9罿n7糂Y曷4廽醲)の(0}i礼妋- RR( Q@-%- !ぅ4 \Aぅ窝@ 4|r誉陪{1鰻X煛舚9B$裼肟%塳;嗉B6珀k- }<鈥 拻X 鉅s党Of漩'犎鯛鋧鎬p袱;s悮 v恲洛n鬤镙
H f笘mt悎甿H撟兤?向 艿})鞪 雚P`I-摐 贄p駯绁80苅 z殘+mf^q趢%轠懸2!
`w╝`#
齤QHF慨h丫)m>惦陑紫:N硂)l&@c韃4葴"% ii棍 u-4鎬hhb
碤Hhh 襊QE QE QE 搭在wj ( ( ( ( ( mQ@Q@ E
p卛E 迶I@ 淨竮Q謱P歀鐨\qL锧
賘吗棅暨Y掭镵q鋃=4{(S笷I贑 g
遉虔
謘 A 鬨T昵覑qY氝坱邶玏-#!婛>HU昵豥在^ 圻馟:oT2l╅@!燫梮~'冣茮]貭拱驦w皷孒綾r梭 (鄿zf s芕靼Yk>哢y7詔叟h~n B幗s冺\/4蹗G鰡瘕:フ尣閚裓[磉 ?L$rPH饨I腰Oк猑鴸 R粮u毨E:崉
#仢'*x4>濄 V 顏c}鏹V*蛁壚M)鶊趛`8?蚀t齏N铡y篡鸞貞蘮鲇,姮9*J搩茹藜S嵛棯E鉥垜豮/賜禞o Y訧r
怗'+拀8 x烳'螺*鱓倍図豬删怵}p>a実$r4齑祦▲睬\筴1k╔蕃f_碴Aa8' :栓5骕辜Q弓墨屼畇袕蝷,奪&毛El殞涉Gj襾#?0^抱趈V:冘%澻
m)唓亴n:玞 唨-LS﹛0蕦R啊O咙\ Y-蘱!i#!&綶瞞至I罭+慝 !`
:昤Gb1_+麷餗蟿5楫 C 卮dt q8n礏鷾S#慩eNX酯b70> 鰁# c$m寭Q9抖睊F 鄘FO5h_5于 f圚7$H肷V鑮+蔷 揸 5共詏-f 闊c7^
袷磧仏 积y8
;噞E甕D簳_m嶡 ,d`t~r S揁 Bg4+涴
蕲{鄊*mr趝}LDc. F*佺,7鉣4 +7],59殳巻幢 翣<=G< B3廧pvS淬廕D7 P0 sF36谢(U蝻;
rP燦舜c僎脆妠暒`岘飁V ]5徟-~5褨1窹櫞T摳v鯛_泳1I耛殛?垠+ò燷扡压戆饩wa鎫8*E2.7耢h戢M{L綪休DA楣 ~碚緡5騄4+ 円洞x掁`稓岅 絷9#+忘 -cP縳59蛕Nw@ ヅhイ((澸汵鞞Q@Q@Q@Q@Q@
( ( ( ( ( L袸歓 Z箫>占-岘J蟉笸狵qH9RGU \ 慬鬬
褫g媣-曑7h誁胘|Co宫鐔H莊毦嫱!?9鞞 啉3\5Sa9す 縧jO 祐襨>3│Q脭9[".3( z核K?66蜾f>[孼]D;攘?蚂J湝遣A赏}}鹚犁N{聽屣
Y俖M援鈔室q@ 4朣BI6_è 0偂镜 黋f轟]&8V Z构|5 嗠明rY廮m緑1s娍w-吂俴F"\
癒鮓都劤9 薽 z %v減z夎艀醐舂U愴吴~晵у ht弎躾R?J@镄妟E搾( d$铐F鈟燎j尫矱眆<灺*卬爜酴`嶻髱倒'2y忼针]鲊 \L娪 3寕0M y鯑5穷vA!k屑?痤i$4蓠啹F壹1﹂C鱌哸黮9瓚巰q@G噇鬬 HL`菺蘫c幵7JA@σ (イ((澸汵鞞Q@Q@Q@Q@Q@
( ( ( (i)i(( (P袳 QKI@Q@ax嬃 馼"雤Tl !蔋．
弆夥hcQ厎喋<% a>蠔衻鉱捂
扟寭抝枾帑郫 [ &辢eI贾,專h 凎唕Ev擯慀嚸峋,]>$业終F:t鷜竡e @ m叿.恣:戭G掵[洢}婠陴賊<峱鰻(,U塺*莣*1b緰ē捣$I`奅旿H 冴1趢9=j?> 衞.o`灿愎窊K崶r
憤刮1戠4_蜜張Z韨 ZL [O9gErI 霪D缠g囗?W廡笛!庢9睄頲嵙萫対狝鋊qU屮}鎗#楙^C﹄鸩]X 韾≦"8 x9塧▁驠皙T窄5kF禰藵,Y-Dno*U<惂?09=雓U鴻~!狄E嶕窕8%皥悿8莬s\筘|C仇勣 m蟄奒9,Ｖ薇*氖Uw腤qeR砩湓簙乻｜a瘘 蛸豿Y,菊鍧厬豟稬墙 w4 も型捅Qsiu C<梤嘑 寧嚒亮85_x_腂o O粀軖Jb_00~q訍r+曬&゛ 镶粈逗茩"付Ａ2Y攄pB岦丨焼4鶪僡桖 u-JW詏嫇竿)扇霣 r(3E緵 刜膠鎳$m愎3[┹
}咫苰9Т?碭﹜慠E
悰I騏佖瓋鑬( 猥i3F(馂罚E&輞BHc偵咤=t:O<' *皺侶 #a埱p1留5疡鐄xW^26XM,高0$鏫7O~聙:
\W熆仑靅[脋'状D^栄]櫗艫沈<9'0C馱C髺;亩囝嶇Cip~Q 銙NrH =gu|4政!胫%窠甬j6%V鲂!洞嫃晢C>\瀝+s to j g35敩7 蒧.N3歉E屈^h *钋舢 涑F?*钋 J w爟跇A軯 邬杩 婋臾俬<巋2顯/T夢鸊蟰匢蚠,鹋簪_*H軳@嶖徣
韎剩 x围82H篤赡\臒 黖瑟. 鵦$ 抺 }纴"=q@ 1\i跁擡u/ 廾犍P*+ポ]C7 T6鵑I%檂哘" 轕k&=蟒銎s澭燬鶃@ =歪I嵩E伎6ys系z< x%妚Q ]鳟x疐觸3ラ筴xKd钐齥Yp = ?闽/$(覒錤c 雩) 匏ck╇>灰礇 胲年佖*4嫄颧p h4敞MJ享 ym减#S\檡>Ｖ!瘄=?卄瘐郑 ;X栚+Y|>$芖S嵢博P'
0+F酌Z_埧h_Xk縤秲L咥a
3冾{鯛r0AU5=[O循栫R粖怓$暥'狕+牲 狒瘭扁;絒T!揑繐N,懋觕Q卽贕$`r>Y晤瞩/^YxwP觰[;]f]?\嘙擮o纨#lq蕊@ 矱q|B蓁Z囶鯊焘腝 脅gp#+偋璙鴌+ *y锂.m≡ql鵒(疨T?轄@(忘k醹O掐/裭ot崬 宇Zi /枻.茴_< 嶢桫 )h(杸)h+讠顛=秿~襚%饲鎦c#$\dW 徇 術椿楉W扶鸰蠏fA鎮皙F9 4G ` u卲 %6稞朑=] 0> Л! 終@)在Q@K2( :S墻 3隢"泭Q !鵻 )F1Hy湚 霵b奪C@敘枈(h4 QE QE S籗i莰 ( ( ( ( (敶Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@d[鴆G雕5邎岢郢]!炪蛃
ろ qz寨E q:焷锃麮w 觊罞3[壄6[抮>湌ru 陸栊参5-b隲对u XP* 垽皙爖撋 橢 y5岞_ $x㈦Z2坶鸊um~闿嫺m ))苳ぶ椕-S^癀犴.5$7T* 芠'=髿鬢E慗簡S貙妴奁我Yザ祩'`$;K詅宇觖T簞晼5 J:娒鴿}琞x&犄A讲揑h-5;物( [!泽躊^U哹e烣騶<娲Y襬00擈}茕確韔鞓?穨琵ンy遖咪穘 涱9餁 縀PEPEPEPEPEPEPEP )i( 袳 QE 敘挅
(
((挅拃
(
;袵z uQ@Q@Q@Q@Q@ %問
(4
(P(
(敶Pb孮E Q( ( 4f(奪(戮轠鴆鈝4絝h飚&悩瘒$`渦閟x驥 3佛禍S達H 暛洞v匚0# 嶰A詠R鴽> 駍ず疄璻 q 剮Ｘ 猳 /A饘R&廱!yq鍶靅 <7F腣^0金秼¤62/u
F釯滠J﹟呣A 儝 k焻' 羊U忴T褣z3;朇 [9 m搥o 尹/ gh鐾oi既#3<榗 q衠字5( ( ( ( ( 擱鈷
(4 耿挃PExn┿鳨5kW鳁_兖聁l幣]紩*r邍z<щ-兆期嘱洣1 >菰 8璞_贛}=擶1秸韩Ml庂臲棉阂~!陑紬冢b[v汎社兑宥珏5咝KIK@%-!J jJ)
f拪 vh%- -%PEPGz(顯( ( ( ( (碤E 4見+蓻H_ 糀щ騃.厾$QEГ$嫕霻俼悼襁CS痘痘G{[埀Ts0V T恪 6k思w酜 xZt积0瑩A
攤,(瑜 ~=堖狱S猏麼撁蚯e龡&幒潿憜3r陿c澖w 6笾:蹧,磙怅x鄠1棐W
=舌S;坈 H"0*蔉AuW桒鷐_U瘪螁含圪XA on 碵ei##L68 5惜岦E
骄⒙ 5_眔]:篇W愳yl済i=h埏o 蝇./蝽恝iN'zTZ^ゞ璱恓:|辵る96曑3巹:w膞z竽wZ^3腰Cnl\赺EG,;I鉆WhO<鲔XQ暮茩喹N#吨u劁炪Sa q'lx赬=氵 .55隩盔垰^;oiwmvQ1!Y0I嵤帘岊蹔 鱶峡佐.蜣 R抖构 Ci 8鄔鐘 G獐 i氒`u]T@J录封霕()芦bX鴄扊箋P秄屢1@ EP(1@q?|iǖ労 z窧R9 ?愍曻溹w>._]i
5Y&xeo.=枘"2=A#瘳飬 +>y礇K壇2躀q任I# 8麵$鞋u+8,nb苟攅%壝+颲+侽
輡:館 巍p 牭綉
F膧鉶8-><傸B駈夆Xj跒64q^X郄,貌伖旪7訋鄡@ 跚臒埒欺胒6歨専jY0FAa睕vC1躍涒G啑 i[挚i鸛笍 1]叿}3廕娿嶂梥叟,!T傂,栙B<厴鶎{1=褵虐霟d碩幫-Sc练焢2:w隌 UyO弖滼免蟿--o痗礉怣oL蓮橝咙{W婞S慡怙傳*凤!噻廕 黾襋E QE RQ@ EPKIK@Q@Q@ EPR袳 xl6煰~衵崕畽h貝 .:Z
灶 x杉琂襥稯縆簉Ip 憥0=k亘 襌欽 ZZm- -!ネ!
;踊P靓\欳謤 RR鈼 敶Q@Q@Q@ 瑁 :(((((乙Rb集P嘮妮C膙鷠瞟彷q#[某塪 (鶚 <滅$ E4毕0駈縲銤"O
P負__=耩蘄a捾m:1餵\檗N＂+蚹o崿K3苭 鋹z齇や褤锧焰<3cK陈囂{{t2膛幵@ 灷g╀汄邐|U餕N呫枪G-{NO枍~(,圣怟 k攰B迶8溠/4P)40 <
\Rn 笋 僫鈕^梓凎W1
寯n醊_ｉ%i鰵U龤-镛Q1伾 玼 @踍峭荶 駶g酼籱鹇鉓觧E龉}x梈2 鱦OV`$g撉瞁 )[_ 圍}壱.爾阧n爇,鄄 Rrv'8+>)Q?呿=2Yf栺m受2(響祦蜹w醍軮e訮à鎶 Z駸1'瓶,7FH>荫砏嶞C`>7 w;?鬭c3@Q@ EPE QE QE QE 碤E !燩h 賓X 缎N'閈w嗸iヱ(掑咶荠[sO览橄祐/~等iV蓦涸71鶓椼 G 聳怰IKI@iE%(鉀瀒{ 澻R鋡甋 , 槎鱅l'2蹽邑奇苉２涰vqLWn跷(僊
p銹QA
(
))h ＝- 碤E QE QE QE QE 6i 尭莎=拙!耍j砓瓟N2平 坼o廐>1#帛驙嵕,@ _p鞶7凝Y鉬惎<~鹱厸*I1@ 曼K詃孆R囅鲘;齓咥 絓L_/")mЖ鎬;鳲>溏隟 瞠zH蜜5嫂Vхm uc呛焤:楟蚅&-\氼雽齣锉c/!T';+o j ≠Wo﹃蟑堽#]C茷 ,w]拳捒g掖⒕祘_2)E锇 _J醸]%蘅ネ 赖#qa侊@ BA怆堩Y-慸 B.嗨 郹戂4赳,餮<仓諨n綇Z諅A*6 = v蒜鏱稥'袣c莖ON輢zz浼;0o)党骄b=躻:`の( :歬D馿張5m[M磰&益騠iUB避蓑鄴FP祇t隌ぼ(葼贤O颩歏 P橖glh8 熻?:雉c" 1\芿 妟 郁 w( 5 /嶦-00.釆 SI(!篟鈥
(镮 ( )E% :((((()Mz7壹偏茜烬}+傈rvu 蕗9在嵆鴩Z{{訰悌J 皣濮眂抓B->rh8q姂洂EC倊Q鲝Jym羵蹉(扞On罾煑*) b[hHdh. G螞3锪缵撏a|搈WYV\r3臶柴 倍婃隱豆眳葧 H`~P樹鐰=@ 蓔猍j謿u枷)gs t?/N鸁A\W(Y L讟"C熞K┶ =癶 |Ke;疒対Z组揪t掑 w洒5^x銚瀞靐 鳲7U渡8 5tv苈材嵫咰喚R8湍;囀<0唏OZ扆 &櫷 溆)q@'zu7 :(((((歎U=
|瑹蝳囼癄 峋曕>8 懚牋uNG稷T84盓9*E蟯 瘱 `馧 疭 z 蝚U 幍p峄
z
菺 O6F{t㏑揶骝'环Y6埽8 鷥L ,d你4_砰5HP勿Db趛声咖醀e礊钐[4 Z.嶘澢鵕Ik驡;/#m缼2pG?櫕 Mp鴀4K浄&exP慉.Np8綮;dMgg"蹤#掍 726}3郀习锿WM搁S讫籔3 5b4聜z G54矆袰2@晔茶剅DfF窇L`喔*x蜦3醍#囔嶟厃 ~訦泯 隬U琞X\iV鈋 N3伻'?止/剅Ami{l忧蒟 膍 佔秉0OQ姇W<灤! 馭勩4 皠
凷苃叹5<7d|x; 齵w (緼^_瘳伏"vD確瓼9'藎s 灳焞 H姟UT ,F趓妜 点<塯8塦L懕8魲?医斪嶘<#遽H"攘 {;鸫笭鲆丷*\SH垿S慙" #突3
嵏锧 ┟! 尀(姮痞^5 fV;T-膳 C$ 詄 3S鉅|~T05 cR楜讗摎苼ZK鵆 鸡靣 )(|,妰紾$ Fx4鏭竜鳯蹊rC枒汇1腼9蟟399>趺=炽=iX 湘禙8膬#8蟸 t閹賯儏rM 1妎8檄S檘瓜AV姇4秌蛙怛m,y'襽0た檇",p3 椰[ n郀m爾设0颹$Vk癒J-蚕 Uh劃w巹w闅拗-眄~!i%B堉湳 H8菰缬 駉# bu泑,.9赏Mek}t 暻 W_駉鞜趜SBau輳麟揓7p淔擉 9,穫h溮<] R敌pI疊4'P觰0慮宍 叓摧&纹K尀C+ 怑 s{緮鸢 妑邬6瑧 藹n 饩愷涳疠钚礌衕)sM 歂鬛迉 EPEPEPEPEP
(犘(F鶺侙?猥{鏬逬1o\ 48*q殩5`3Q矑sSy楶1@n呧歾d簸Pri
?.M K)&?7 =% 談鶓G@ 妟 饅襝jT憖 '亴P垼蒩姴沇亙UP 1澛1@憌
X ,譅塎@,膪U觯qsz-艟-?J4韇笙箹嵯栠t熎,n擻瘤=鹕i鍹款鲙:
鄒?H辎/-鸡y +1钱rs?峟x[莽V鹬x$觗朒L'i.鳖脎種}{Wk柨饌Iu-頭绚H%_g蓣菱肩:墖 "矇|蔀k#^X顖轻@酸-{滦Yj6鸐賟,,]0?)\ (9#缨z辄;獂)|璮x'GFRE銎1畺O凼08b
8霂⒐藵R
V釱9 B 鰜 u龇0軨婷"轰尒:姸溩1嗄簃じ綿 0ń秲萠j"^(藒7 n跘鋦#箅酋鶺獲!1秾0 钎ywO"vR罾笪c~z惴鄮s瓯憕個%QR丮QR +燃}n&*(豣@鈂霪`紜>0x8J2勄灲|:{鈥=x
v赑)郟B襜づP$SH〩ㄈ4詥 壀#R礑聙#&R5D 仑ㄘ奦 P=Wc箧-殔 [#"95$崈呆酲寺悀 9涩Qw濅沂踀~惮 喞j o銙H( e茈殱賦-LA$ OyZm丈Y箻 驶粦 胱u9,mn'+{X鏰鍶v' s蕃Z牵j 3.m<玥c偅,麃岭驈с@ )猁MF肽讝雜/阢GW惓抪羪 冏 }:WK/鲺跐虗Y徦U-箷鲷'1滛鳝Cm' 繖祪NS-尟31汨z庒啀'鹰嶺搴惽鍛/FeU; h嫡f)鞖=X)瘤齤詪$ㄅ[j侧麩J璁-:]a矚9 ,蔽寘O 耴嚬y <壤*t
殠咯揲V(-"l凘1肷$焇灥祡%从泸驮譆 鎅蓠阹O?昪L0蹏,:詃檟甾!:趈5,襖)}閸荐3Kgm②媨洀穈n%1戅w6*{忌羖:f4-V辿 d返;橉^Q湏YW楓趧饼畐攺昁v悁讀$楺煡 4鹃牢1_H!鼬V芽侬毼D憸c汑?纆) O t铆- (庺Q迉 EPEPEPEPEPM傽限鶺亁(馿豟H`;W 嶔癜垅珣 s J臚瘒"洒 MJ珖榿霘c佫箶瀒|J铲嶄嗀':鯇42璒 悊
茹详红/捘4sj满+伧.錪ee龛 葃?啨P>l斑-L 砹4b2郻 Jv裆
Ц 挦=Fj芅*t溻 o("莸膴翃昦袀9蚔兠6fg嘠K攂z`c?铟5X 褶9#罬e<Z],膼鬯鶀^~菊OF鴜ㄩ:ヌ鎡 俌憂U 9卫' ~5芷x霃$4蝘^酱&阁1簠 寫廕园鹞沞#25陀9愊q哷x槔荍詌)4b
S摇QV(>8滧*訟?鬨曣1憕偧枫8饀>逘宺O&9献 _誧 " HⅴQLQR紜硘a顳#1狍 My鏖捉{ 銦圏]o譎魓e
Z n)6蠩 BED卢Q2-Q5N薖芭 DE1匟z覼 e╔|諉╖+
挱8╲礮F*gb巜 q妱"m!殟軙噜晕 *縒溜襽&憄洋荢汑'狴蟼鞗 :mp _C (餧#R(PKIK@ 瑁 :(((((歈HiE 7' 翸p哇瘂-舣瘠燅S哮P;" ∽┃n,趩衫
鷶-R懶亷瓢鋼?旃尨跜m癞<鋎Q$Kq d9襽8腚mF'y0;酤旦;I-爞X#?<{潨佖d=k_1 S炧萗鎸 銋舃>赀G汲9遐\n蟂琅 j氢0i恩炒$ u$衠鶌侔堪網k;哥6訙-"奜i趓*{4iJ蠓'渟侤*涠彪^*惑C秊< Hs 8阖{P{%訮[4踩4檹@z砤u濯Mo"}譙恔蒼 <1sa Mp
犥_錧<;溅崿]鑳O觰-4A 醓員浱;0
lt倥胹S敲f癱橑骦 赛豗QC1闇駣迖鏍 j东臯 疛7c@妲E臗n蚇瑻*KS1*LP駨54g5 &*X蝵: 葝g a 裄抓貣k r馡1柔俽G甇宰橖sl&訣?鬨曣Pn騝還跢q8 芝QQ璍 x缒 c吝锩 Ｅ{(桥慵悘鼛(赨j@( b欵JE0 垔崊LEy鲗*i 60!詏>dp膟v
炟袭8l亘^ y駜^哉厖浇倴J5鷝 籡'喖a蜡◢?晹E睖|紤実驺 细 詌+灈Z $&喔墂 kR薙对![I6鋎`$g鑘Y~Z寧3R藛 (╖:郩g8d`j9+8◣鎬"$yg5焥smh☆衫g8 }覺icR諹5除歞 xX倹y d搸;鈥 剭$K4yQ敂` J答腆龝0z
4雿*
#I樕o,) +*矢`A**枪4駑ㄈ睤敱X紭,8'L+9 TrIs(+ 畺譋俳嫆B丧涤懋叮.$%H 麋謤2-4醩 .医骼q| i9<5銼Z徤蓪pI9痗餚 饖Z悃?蝷:5 -%8}趏z Z(爑 (
(
(
(
(iESI罓晻夢駴F|K3 H8燎铟8烨壹V赓/す騱潳鲦99US搼毧qw繾悴毻,RB趢&苆h(9鏍bUA+繓14r&马
М)鱎-緸騾薞b3屻蕖彂撝珽>F ╆
U幨6o摣XiR5I,葃晤T宷霘梏-v薥秠-\塩;f侫!l懙妆?晀俶C内繅oPG 鉳nRǜ薬簆>缓UO愆戴/壄T槛鲏aδ洐g(6o d0 騬阸 SⅢ^]埖M2=Q糏DK6H 0H鄝 颺爞J 埃2sP⒎z趢& R(≒穤漢>8Qvg) 疭岦嬼暹 夸H 皧韫+俞9E
磿:毊,捗mMq,qD,0UQ頜 J5 @ 叓喑 M 砚粛S渠 訉褝B9% ) 寁(bB抸}嵯>"皲埣;zS踛k,揊筙鍬觇T7*OI 0z浴A#1H 9/峦B\瑯忍,墼鲭 琊2吡1罪v韷伨駣*鋠咦霪O'秘|# 鱳w)s┸(Bc稳 惞霝2H > +7[誱碷*鏠絵栶. d瀙 $侙謮卖庥H|-碑挟箜?(囌+犄窦zz%資11#豵z鳜竹W堫H粨T 駮q<(里q+蔠+曡S *咝-V]N%奟痪l苝~_簓:鐜焇 =/C詎グ楳{$ I藨=8 :薵v馷 h该(9 凒*)vYc 斡)愪錈篚 |骭誏楎蒾<眹鏰=蝫 d@ 蒶u
醅S尼鈋拾9琞CC幷畀,牶瀐<媷鵵擎a瀲 g毇瘌3x6輼抾9?栉謂h响糅=m%諔%7Kn鲶!b C弤宽q拳[+-&贲;[smnk激zd 绋畳lI俁 #$dU6禹B驊c<(拭aμ稭mp\吱I>l6優暊`E8 緜*翻 Qi5 l悭X?7cM ⒈稱Q縫{U/k歭悷糋G赊r}獂頇恵U雂夻鈶廧栘靪葜(B胨>勗嗆 蕇N笶 W畄M0G歌M Y矘 灓dUea璼 覍盛D\ '轱鳸(&蚰6饞舿G廽塴.XM獿娨b0獱焋c瀤 w:陌廡痥餘O-@q袑騅M.滞懀L悝y痜鹁 $`鈥6A槯A乙RGz(顯( ( ( ( (Jk )鎿v(+Ko磆嘻>P靛凛M{4B纴;讈?m本负髷腬 9 歄;P$s穪Q 窾 OaQiZ茺繬s0 聃珤晑Ab蝪 蕿芼?p懛翻C保 僝鼪!u O%z'鋉牤╆x椿坅62L&CeU曊瞴9pA圜黻 杂S餱"YMj慬G
堾雳RS'nA羖@ Z憡銃_gw╦6 p#m*7鶒\荣Pz 瘖雡獗 Z轣+4浾鎰籱.1凄7|阍 缼覮嘕浲赹-B6髿1"X衫 鮍訐來Y&堆跸诘浒4P蹓蟆藎ぎ
9邹布E{輔T轲嫺鉓+paw20 <s蕃帅x=N瀶Z+K替;怾穢ll駥q窹隿ル:}惣庉頶潙凨誕睞9T''亶&?kVz]旣韓de6[蚨缾T痲湌A霟撇t聴呼鰒銘鳺Z砲詉V梳蚱R髮zg撚姓7:剉呢G3N焉鞫寍惬詾?: 式鴋,镝桱 "L 骰鷯佤┾墤鉽b1箑邕娨僝巄M本x萧}.g 螂
j蜻,抍'&R 缭鸴~|w_码搎漗 薾鵥x頦隵耙nZE=蠿Z莔i舘垄L,3臢]@哩渿脉# 荡
鑆馕騗箉/甀 bV^8 f磘}E乤 -磞砷驃桜#应粘yr 鳈91u燚.'"鵧1$傓甲=7> └H` ┥蹴廕鰶;Xd嚎d@笢n绌1∠穁5踛>(竃w 糒6prY 酅 哣昵 I)0p3憦笸w夠揟汯u鬉\煍鵴WV曦>f.rjE<誸: 姖(耇姜$〨J ┈0h<稲昰鱭
doA\饯~*,r}Ⅶ&8髑% X莢rr3寑F=sZ&k沞婠 %籋!悈夺襁 惚5'嫰t閏秏-e杊,qM笎I_n74Y闅吊盱肄yR V馠IQ嵟#駚寫V骛Η瓅7玕聧!i抷妻儜咑Z薔-唻d袓:,塋嵖摐u#>姜膺鴼e灰"a鈪廃qn9;PA梂洱邎醋蟹0&Pv$\婌#伎S阶n靚L煿VU堏擶囫猫疊鹔虓j呄V4c
P}#N扺v暗fuebaRYX扐恪$擃j诜鎬$穾+xR(鉋
█ 爐 zW東@q予喷6蟭> p儲G|鐪宷^!s鵇 6潳秌妪wO酱栅婈耓id`鐀乶H,$z PO=kY芎柅yt3 d/@q瀮弓
y衉緒,2?&YN靦荘{时询eq媟哿*.['#8=+攫諟杛H驰禿$駬怤釵n緷H m正暫剷尞3)
粑9玘癀憎v7瓴蕩tR扒'<s貊畇\檕?赗L1B#;#=+囸y 杪5y;@漤@r}p }-恓7紾>輫嫚鳥;铓鰅p仈(9n 蟎q仞r#儻z竐嬎x&憸D莂 =6Πu荒钠7沷氷rNeAv鰥U芷7哷=隞跡}I赾戞 W> 帚绿;柠舙~嬃タ>yN籌#冹銖 Y熢鳅U坾1j檵趣c鏍 薕F鷅D鲫bd薭H倾Z鷚埈惴惽E綟w 麹z擄Y镝Lh_
灺瞣鬥t稿攭]#]网
魺j栿 记荁渧:}{灾轢菍魼H按莭鷬鄚7┙捶-戚膁它G趑
<6鹁瘆﹠$k堘徤蘽7罄锟綩0 _岓м蹮)8/ h`5否'詌曍.blf筯錋b3竻蒕隌众渪"L缲U.V}k棿憣{蕼憸zT謘/ Xc @ r博 6j羜96{粯#Hな撓55!$\H0W5F
乱y.t雋韓軭 臚q誶8 qX5迾~=V赗p＼ 皂t948+Y,Jd#o鯜lpUH'駫O
陑劚 GT硸穔Xp齲%$}釳tIwr 匹婂 L鶳vZ<6ざ亘 顁皖kK . 3螾1@ph崛f∞ N CW阳輓沙; 2 P拎銗j豰絟/鞞 5徝牖
a甡苟氂(x鯤8黎1郫~N9~誫砊穢b`喟'!摐巼 W芬瓕 2lR膿蹔 +;樴糠栁G邇+)O攽=餻H幖寑q6? R怟玧-燛
頵P钙H1零弞韙_ h>仏櫢{墰t3済兘S今K媓u磼5怗("\0dtzs\.眘螨礵晳誇A赭]7蜘蟨=K
X鐜U嘷Ps^G 幊-儁舔F0鷆卓簏z 苘贎R襻 糉 = =眆撆Q刚-衝YC簀婙掃$F 焣@驝凎+2鸇襲#烘u翘 8 糸T[腞#(U帛;BJ 7牬哟- v熀==p?*痷-4 既臚v繇毬恨駶頀;毷荡竜8吴Tu鄢{兦A@ 鲟繃虷0N fS懺 攽蕹e簯畱7 5KM秌4x骰败艎廘煡%涕昊癠 Z簯懺丯绘轍螮颰'訿r7銦旀爳 扩S粌@B钷( MP赫Vi杚鶏 @x"秀笐f櫄@鐓nU频K[4DL銑 鲕\#O姇眄髜鋎佂i蕺龜酑抱Y麦B9鶳# ;逻i峏螒1$鐠2H臃|!{s+w:F& X `闛璵ka淧[\跰p睠2蓭9臶c- ,*
鶉妿M"x?x,P &5,/\R侔{h僣铟琖冈作M h 僕X啮蜥8.5瑲鍉.$"f(珜 sj訵沉cV(偽x=9鐬={5Λi皻`佄遘{T掃E=靆L仯/埉b笐坒@
1跷~咖鉩 仂鞻3 譎 8?8翮5噕w^zS瓊 {翻 kE猢赗?w荘*馒朚3>堤A#9鉂pCN剙1 u3x潗)?婁*s濞醍v0m惃奢B靐v渢 趰虤軚﹢璎rW犻Pj"薬媢X!S曽9 滬
滇45>84, @ 8 t靰h
竺bK<xW磢?-姦椥
腼-i騪>?]"旭蘐授i.u)W澔zV壄Z翌}
鬕C詅5h浠0) 沐徢滜疨i莎0鲽悉捔條{p1侒u鐬s锧 荮Jj潰 粵忐錈跹繚w)荪Br 滖缸
j~Y?耄:眙/C 袓 hw4儹)S%(わKI迉 EPEPEPEPEP(碢{氭迪o牣榰5蘫_顸逜@*@56邹撃^3譇廟笗韙貎
莁糶
婖崳viAy娾鍱`羋@094鬻 毙~ _^kvP躪+<3瑤N袓J 笾Φ馸━#A娛]SRK烓^@睪 瀀r'廧5
K鷀亡M>O:;5BH9 [<鄟墼w5鎤7l壮/婁褂炇嘨 9丕 鄷U胄 慮摢x媚V3kVVvA櫗'7毇 6侫鐜灁桎`鎽発渭#疎4汍尩I獠盎# 禓@捈騀燎\ K謙韓>檣
蘡飝m捒Q詞4p馢 )g塘/R瞸yu$儙啧+觧,菊 G My`d 6;c>縡
~j 汊饻鳅ツ痯駾 (玂G罒( WHI$馧壽怶 阃刍> B偰 抪詾+ K鹯_紦'`PF 绡篛執誃帾儚髯讪|9矷|楦皭d鸋聙 >绻#镵v蝝 翟I 螩Ue褧梠* 烂婥葐軍I 銿;蓴V j翌璪\巋 YA$暇0=1L烰穂堁A'耶F,6S挥'奞c6儍'瀙:W 唭 鑙*垗糤0J\皊s侼N L层逘 Hrh绕焬4hi-ソ蘽c穣pA$栞寕# 譋犃┛膇/.传K 揈u%E櫵R{┝
1光 i:鉡5%腛筬B让$d鄍Npy珰4Z:|Gw.蜙郎=:苺6 勷)s歗"瀐蓀他A;渶; 习霪W'錻 唫恵戆疶#- (p:P]訮W"9?坋弫u<鱏8 }}> ?胰 5 T7伒A鑺聃5e 伊 e喵疈 N笠梟z8*Lq *+>鈿晢 崚9
夓
0jR燫*緭m22 GJ 卬琓1Q+L)9 Pk憮抭QI燝# A禬慉lq@OH#熉绖&貯雭Z 磑# 涞o 沟夓孖辷講潶>$懱0T滏和Z-籉 a<図Zye旾]6憬 8鴉踹 垖n菹錙 x簘樼Rd8鋸jl劙罓p鳩W嬌U緜環稏扙 4罖ga+VPc穜縷+懓k－9Gm蔑廞@ 寔歀鈽2;y$}=滪l洽屝;$栁B彿
s系s 仱簓;姖滚陊殟虘 !V舓鴝链玣/嵨s佢4\ 佭$憸) j@饰Z曞U`(歛7黂?殚 捫帞燫))u Д0髞锳l魻u_9恁[m瀪缅 .靟焞讏j)穻泅屩鱒@G
*d 简: I+車 嘧獂5/ 趉っ鰀\A gi閮詃瀪Q uZm铁啗oy5抠辒y[睵 @'渃5i~S栭OO晇奛 4蒞R啼寊]秷J閼冔?5萳喉 嗀柄P焃)GJJ (ィ 敘(h ( ( ( ( JJZJ ┊gX 忲
閲S\纬披} f
恟MD鎬 鏆M( i
z觪瘩N蜇逊 h 蹫磩b(!8ХJ y8,看 奎
醅饧徢缵@鄃#<}榃 祚歍`AL\傽 臐宕鵸5)鈮⒑餱伜冴_V鴀ewu［過3}毿8落旡诽P 0頺唁; )2H 鄬僌迎礇,mP抭49妞O竔7z磄c<儍@尪摭i冷R#[詨钅koap窬琸)6懆]拿 0 弬9诇骪莯銝蒜%ヶ焛$ 馕樯?trFR=+-飙璣g捣櫡恃 S#z O謤9霘u狪﹜綢粦m鈞昛軺榣|擐Z跬儲DGJ骕t父kK╩扞櫠 抮I8鋻I甚疐鹗N4+qs(朹泂 煒銇韸 ( J)( - (顯( ( ( ( ())i瑻 阫氈 泷緜篠鱧欀裤砭個2暪=i 3摆 B!罄8*h 遍K酯A屝h(4敶 覤/蚇"X踛v揧^G鍭( 憔A 腜.秫_泶悝~焒 针$^ W釪k^确銮萚蜎垊圇~鐡^醕m晞6扮dH>漉'4=p糦wm﹂戭浇V苭F2 V$渮c5輾驈 =灧圃蚹 胐|僲'禛豸嗻墷蹗\攮 d必\惽π＇1婋瘄sラ趠澪ㄍisnh!繄翮
6痶'F9鐁饆寰 h~!觮鼺3"氽蓂'枟vo@}粈贔A僒~' 鸇 )2郛刎900? zW镍薣英詂赞%叜鎍愂轪nYX測d w x绱#a唟!# .;R鸕袄軭#4 R觽鎹尖 ) テ)靓9鈸8&M bj廿0犦1 w也嘤秕+晵"<>籭s■貋b爍娀珄",F)=1謤6a穾4
0)Lb滘|
Ua縤 K花l犹晙畘鸘乖雄倌臶俲蠅`u)&罳蕲i植F#堖 魙<踚扢hm
)7084藱D1on個渰UK!wy2植畊珛叫Y求t虲~驽逢 葑 Iq狹z鐱>@詵 ~楱T聘雀锧 f祡owpa嗃s卬h糙兮S舢n)4蚷< ,匍隴腁吅9$P NG岤古 F:鈼臅6
!z7挊=h泤轂+庶%>骎謻荰傊5晀 @ |X駥ㄍ 7伊4k$R!GF 癸xi|-c鰬p^S!撍贉1専J尾馞鏐 X\憞_攖9鐤5 啔埌:胆$/ #灊詃j,.sO$\ uL9禰9u t亽逡F愵$I亶囏鋊 z魄韨3~惀;,儞<籀絆袸迻
;袵z uQ@Q@Q@Q@Q@ M"枌 O蔈sz Ko牣 Ms氉鼄沸POz咉亥5 瑀歗倫敉 歨4笭&陒 TN>\笈铖旨浨^.状?G漴轉v!僠e`~f:鬪紷森/x议?閃n畷$滲# 凒Pr6 .獤ǚ驠#抋湶巰鲮9 偔叜^ 菤N梶,&磻.(櫲翳*
KV_鳹鎜j才%u 粫R21钱y (迸Gqgk╕薸{s廴0袢湉\梹踋.潈v扏ㄐ`稸 扚襰蜪5卒仛 珈<岘6Gx锤ec+H $贋=噅梄餲嚨孙秊:jKp@S"弧`:gi8'碍膔荸 V椺MB簰鏛阐4矤嶖儒H鞘N3荺g瓍ん2:Ss@ 性夾歎P 闕雩 妜#奏f 噅鏄 o5峞廨禊mrm U掅
l 戵 儳s5监.a梡<
戨 91UR絟
驲+m b洔歱#p moS捬凲兘胡
叵-廪N纴4[棱貢慮@*q跟 Z翅噙a,9锧黴荍R缼>磁8隞軍 Ж\C7$^雷5c撽玵8僩"返沄烵pFA
3o叿A湡Z z謣6";<{U碣;i'疃冎9]@Q褺比S苉禽9蟴呛疒\~穃姟m}wa-溛dO9漜頝i噌奢Lc r殺嗰Jn8翕喝裤躦夜-U扁x貆3锱uK魻幋岾E 4-.H圄)復 A~臟 :婛 :,壕嫮Kjd鯩疟B~頝8鼽k鐸9@
ax{邻g%簘>=玴bY乚萆槿 k I5攴讖,J#嫹eU 9## 諆=暯菃/t84魯*揶]啙 Fps崸y$ {=穫t8u J鬧7潹E,W懓VN_ 匊V _ tW壆7C潽.考 ^焦熉迩劥nx -k\蕺槎Q闅m稛 睰 糱$iq籬磝 P4t爫4潸}劮玽璿 r些憕崒姭{燲j3[E6迋U x< 諱蠋5;kK7GdC 殔#m* 癛r牠弰媅X/0拕$8m匠 葛u!氹J备渶 槽1荖H:薐灿鍠KK;{v樻C J呄=p9: 邯jU'屑@0C)p1欵 6 覙T誀R鈥#Q姉ni Н\R摃9虰X蟢 洦A猉jV:~磱樛炀\7兪6x9殛8菅4 鴼i!葛鼁6砽宀7Q$嶃启堇q橼高_榫*I|=ca6穢Wr"o4у_仔醌>%}④[k蜁)"-?nc'眝0荙 绺u{喃/&煭_[詰剪棂'瀦 撱篹伽堇cp捿埱?醑F(P 螓岹P"5o
j6☉y捦I憐g'侒{<[傗+竍竵婥*嘑*W 8<夀0襚詌+u X蛜 a鏸羏?飑f 5[媔c錨6 цE cx跙A|晕~祇C_鴸Dq苡[偢湆鲮}玭Oi'嚧雿[QK浌頄A鰐$托 亐}裥鶳f眰欧u畕B駘懐塃呇i"R崿 n陵:}23妳|醳.珺$-锋 鞅 t觪懮^枣鶕=+凑错-/陌nhG颳h8 +`侴犩g4鞓鎭$娏捡n彚圳 _Pg2醂穚2p }kWI4韋>焬
蘢Lm捁 A4 鸚-n\|砬鉣蝺 x郷:b]斔膫佼螮埩η21rO襽.徑O泍
)i( ＝wQE QE QE QE QE 贜敶譅5蘫?顸秦WN諝5燌鹢牋 v濠蝦燬{@ N 襋 0)艶穁 巻(a蝰@ ;gz"噔-儍@ 雭M,郾妡m喭6F镣 歕P#4b:R哻謶z試孭
8 鈺x 崲榙2o}祬s[\畷③ 齬t-筐*喠y *0肷 诰筩P沚禗qㄋ蔬軺頹 k2怾陹希璨G磇1<鐿玩熰1呯
寖滐xc罒a笍X
蔶黑 )@"穃兌41徑尀k襽34L鞋c秤#穫1颏c陖O逛院c酬:吢[贎护曻玉$ 9$鉅喀xkI汻.V#鮣>;湋_'呛棊u碶
擠媖@賆签鮟 J 鷂罏8绸逈yyk6-旘r\佊p'廝FN+_腪唗蚙鱳夙S{芚 $侙讓嘝瘕锁陟,霆;489+Wb囓g銞钞1 滪樸齞鬚q蹝輕
q簍:熌? I-态ne笡0? 0ｐ澀緷g
ガb8!@垉 喂?吘M@7 餑 庄9黴诨)n悭 s峵T坑鈳Xd 蘣 《98瓧-祄J贳K觨 遁娟$ Y3$騉@;9%穻^ ZJiSy瀹片IQ邠蒲砷蛕棵k.肼6帅C 3Bwh@s牖S棉%揪>.潹莏単 -紦瀀 u1]慢赻磥.%8#Iη" ==jP0(Μ狂, 砊-螖唢毠m>dPI(@臦疒Oo慔m潴@Eyà抒*>z襃08w淖秼 ; 謻噃恑0A 娌麱$>W 求遖坈 N>癞g>'浡歕癦媶抇/ HQ驌扜鹰t t婓瘜3巅A/觥代|瓪 鬃紏m簍飆襧W袵$zx 粈毋 9 9#ax稺馯焺V頺/蔽<砕鰍昒 ;騒 )岱桂塼蚐X峠臣稾掔w"R 鑄 ?菸3^杷
h襒躻0煝]>fЕ >1S 漞茹 揪炚⑻GJoCN 鎬抸規) 8@ 纺碂噝 F: 擆;軳)`<葖迤ec鱃'乚芝j鷟瘗忠銁n+G 冊
翉峥勩)SIP迅pWelv!槀=枢眂痣^諜c伎塩
)$熗駸P}+CR锗4脯粽簕僟郀uqr =zW:&櫓i+ボY苐`16晊鄛Xn4詔禣./澚U$ 熐=齢碳8鲵x熌器T0甩L./m砩潗;Q濦<
8/聪入iNdyp翲*濚簱茾N=峼諊兇 6镯篸QHa 踄1
rH娠Y橡寐苢"鼐啭珑巨焅纡 6穑[XF栕塳#" )悟G蘃啾蝳毳{}0黖慷皂碲;H悴傞椦 T
龄 \tW饁壄_+ylf6(U磺on院焸4 bh叴BY]晻 儞寃S@ uj-沖駬琚!ざ. 腁寍` 鐅=穊闺盁瓞t駜竕r8 V繀{f熱
K觧4鸎%K{)8芘m9l绂zt膳Wo 鴕K(M图N$~t ~锠?穫覲 是5毫A 声?)U 餽鸟軞< 嚞醐b
鎣t擙&遞"壊xS磜 设j掂_x渚 lk礵墛 緡 E^恤 +闽峣y*莝扞.}I4狠$揳5+a喇肐 恡t:Q欯x( ＝wQE QE QE QE QE 贐)i:P畂Z_舳
劳s谶鼄( 璍5偣 JN G挧趷悀,仨NeF迶 衹iO 歺賻z觃`P!颩~[4
F?(W錤 f歽 P鏌寫Hi棱 FEG#琍紥: 3崩P:抺
%YE,N 等郗锬灿潭侺\_#2=崆1 滝鶳譝殫.[G饋S!瘦j3
:鈸懤>慵鹱偞 踡
-虈}蛙妓p$撤S?L之嚔i啛n怺禄U~г灓5Ａ鎬侽5撯_閊堰S乍1TUy鬠 蚈簑嗶y鮉Rq
#撛膘;撻_"芞噸u圃/IH攎贩輹厎$濱膣
浨9抉址鏊ZC數 蛲 顊崩肾? 约C !〕c滜 X1 g腴Z 钎臍票 r^H仩伖優Ob腸轷殍浓楍菡譂狒-6-鏅(a觩1磅棂9壹撫邌張|B&漄飕娚:y9诟=rA习>诊:叴z厡鰏a6壚8%X`ㄨ
焽t%o) b飩領浔 d鳅 ;P挳Ni菐)0 贍O> 烜5MJ]H\塗蛉#'vI蹻rH鑬 寫PX >1菀镏'伪騸FS黎@Wf瓎,及4' ┈i咑,G&3磢K夕^Gr岸6g<=椴x烡鸐趴鰰窛l虂鶎/掭閵A馝謬￡6A愀掘攒珶軤萵0y;蠕v痥餩嚧-;埋-煋z穛f{朙 ny ^屑U芿窌X鎥凪"杴根r峻战笐蚥棹 把す{h源8fE蘽駭R 禣8菹 宀y; 譝坡 皀 啱揲0jR#M2S儍 v84T^0(F`H蚡x鲛,磦趛鍏"撎
3渃恐穵馤脦 bj苍0t_=恖岲膎`T巠<={諢-猃=7頀萸7栻
9 莂b")q@+歨8勁4- &阷鎹櫋~(猋k:U鼏=J捂P粖C:雬zs\ 墨麧?羨弅'栻墭 ~V8a鵚g鄌躼+L竞詶K箾k=芟愬侚0H鎬=N;獒囊) 爌X`)9 蹢 礿)c慘F昀2y~^Mh>7]慆ah鷰鱇 e;A?<丫啼H孎咏?^凯 {p弊7尟 轺w 街顄k,
]熹摀滖衯 襛嬄讆$2N讝 {ZF yq癅wm#畓笕 (趀箑^ク樉{!怗濲?L戼轧z'瓅鵦ぼ隯 麋E窘'晩 zR:鋞<湆慫z浇 夵)k┧2]5狤p埝rC竌 3顯 抟6菝鳺臯*睔贲ヲ葪' >蹒pxv葡菈燘鰿L及i&冺 l懾忣)琦qU~ 閎O牒潨
\C3M*悋z 觯'蛫?=碫x稉㈱]y垅 莨pzb诡靮s鬽曚W]@邰D>爩 3]枔 桦屳學c閝謤4嘕)GJ1@Q@ 瑁 :(((((覯:歨枉
s氉7${
柘5蚹'-緜2]籖2Hyjs h脞=K勧|3鷭酶 Ь=~`赢%幻砕xN7谟':!}#u襁W哟鸧2;8 xT$q犂QS[Z舓m 0茟匘E ( :
拃僒5峖螦.;鵇v盅梫$ 炰軕S揶坶3]軯愛聟鋺@闕5騡膹:远G具G亸侪硞唔蓛傔佨
>聆ｃ璥躈L60-mA扎鳖k仇肣 I瑇傒]軴揷:d(!蛹j蘁銣$`獯|▲嚸:呏搚\h&阱]0嚡-濬?Rk糹緉3弞O34 燽猨z:V檚p 胣呠 衫臬Y蚢 壮P魺i簵唤唚灯nB{=k.咔z}顛u┷[^,俰`%灆贗狸OЧ 7棐瓒椫 崛/34惰G樛侫?t廕 G)Ｚ
0(0﹥nq u绉>戓//塼D蝻 -,k{*惸a炒'恔姧﹂枤>厡^U碄霱疟扞潴詺(靫/*M#瀜J8\P鏋*1. T2鍉aAzR7(灘kZE艒趩奺诶齭鶄6冕v漦,b怫)|沾y擺詟9銖z飥9Z 恻K郲=kY嘫熬河u駙$r
閬耀Y|;泊揚w交竰雈俉湯拜尪q滀f籘LHI ai秤+/囍I鋫X鍖萹蝱c 饙t壮唅fY$2 r@鄘V戛4鱹腜7嵓+痡iス ,樟PrO~檑ㄏ=穘<琲Z
5赣bX》R
$筮趾E遨袔) s篪b轔茂, 岱61崵d滫珂#岘啗ei%曥M鄢崻N0 u磏該骈@
夕I鈡恽籲6b0P~$u蒇Y趇霭資G遨@#L摰GA撋鍅PP瓕.莧酇苢藓%3ζQ/88鳟.讛~? :韙2N 袓 _-&9 J(
;袵z uQ@Q@Q@Q@Q@
}0徿5碗#-緜篊
s:1糽 聙2蓖 P兺# PHF)1颋H隌 i3O<褞( sK尞)腞g "cs袓柵?z 垳6)蘰=摐詃g孭瞅Vi$uHfc爑$ /*9舠堏牥睉用V抌鲩N雮?u%G9n滖5 o$ 侺3鬽I展笀卓最ゴv盵勰慍H袬UP0 檌i澕pCG j伬 偋 +T3O/4$qF茑( 扞*^阵 漂 |掵WF燋h舥TrX> 還螾@9 嫙弸n茟"h朱w8鸖兠鸀丕鹩烙_菝耉&遧琀28<6??R=3Y>餞(訢1篿P熯I澔削銚>冘婘鑑娨喾"5
垔 0e=hS歴sH 聬 永銡尀q@硗Q謚(磵2{閮爩攘zAW剁汅煂Z沟疱緶綏s擫1另髄+*褴 吁 t玔0$肮!摄 燾8锵7鷯稐c5盱hWs鄛&5oh鶩,睲k48吴A9 u?熲襻 F wRcec保t*M形哼6Ys滳F鴒仟 朰缞:bA$ s腠襽=浦U憾巘紊8蟎殨W-僞_﹛嚹Z棄催 h鲬Y塵ci珧 c苣餻6 c炪權韓笈q鴩臈柾-改舟攲9缇O2.闌轥螶 嗉 囗O肰:依Zc1`0d躒焵|9{岘K+鎵啍槕偑;佽k,媿蹋$搶撔Tw:厱どoqs 3I-d慣綨0牅濰 垹 豃A舒斸挔杧t$k渆纒H .(B AO 5 (攙4 RZC@ B蝤ヅ 狍趢雺iI酴 sQ概 +D賓i|舿@ ]齣6魻G枠 T@P;)/Hs宐渪Ｌ Dm/^)I4ug i鼸5F4 @=jLqM屽盞'' 慬|晴P g氺4t0i袲Hm逛{璻)d 兆i_巰4Ex4 擰E w (
(
(
(
(歩i
8鎢焙>偤c鱧欀讣o牋 桔1奊#&囙dSdL9 S@*81蝘I覢i9幍)鉵;淭qj颈:d簴/梠 Y鄄O(x揫揌広治莓u[1Y@8 纑蘋W 燆GO?A醡',|軯遌3iヤ摀q&瞸醷喒柜v]WQ翃-犌龋嶰>濗^姭呪v8&攰!汗娛謐珘(!C$1繳$焋+鋙堔8格蠄嵨 z}惰舍3髫g泴阈q汈邚~6x6.TkH咙7 ?幌$W淈7鹗牒镖畇鯧0沌|羿擊莦 罹5魗/硗A]軫
幑靀 潎^ 玣敼sJ -!|) 24^h#4dc家憵w猗
髴@*章:謲- N炊籟7鵛P7g蕛狱k<溩忴懋,轲壆12DX.蠼栖麃専錊 0状恕鴸 }驟幺建;@ y 韓純炟膠W嫾_鈗uy趓亓!E[杕蝼 c 巎稻應x吲溪犏d篯澖Ｙ湮 +F@三鉹8郼絋痼x焕kw⑶嵘54瀍侥! 朻1穩pv戇黦嘨) 證韏靪$糮忁g?Oz襉 疝嚘:{_]D媖3J@BK!`O' `u簸犟|+怀6翸^觎]瞕` 亴銣茔页u 枀希;Iつ枔i贴k埿 簳9滗`s躥:oSoA猃~6炩躆osg e| Nx橛纫~ ]渔桳痿跄汿.2 乫胗 sL饁憉/堛縊
Cへ+=蠙玟漶2~|n*x{酼泒цW褶佘Z茸;昰墣懘r跳觃今'-u3o t勃垶B顡|湩 t&暮－xE趸K珯奺朅硈ㄝ礨.釬H:鬲 謌鳺ij歮宗`2&m鶈B'
t:睫丰仩汹#"H偈*H!F迍 4辥 膾閦N妴搠穮0
訉銓煢
q~)馣豳瀔U窞
E"p徆X靋戼jmB譚格围'埓mgS r谂h 艒盟 6<9"瞗5S-N-
?礦T禭^M║斌亴g炥朕# 訉 5涐à兟贛佳紃莋8)2=璥PA;欣
f2h\幤奰Lw 426觲bI9c龠4
.[塘0JFI)槔4 }邲4/\O
覝(I<衖 /*QE- /ZE?5/jh岢@/疑脈i甶_*簊@墡pkx鱼Z渥狠+嗀裥堺碢:Rw( ＝wQE QE QE QE QE 贑KM4 玕殖胎?w婃醅y捾牔憡慅罳
幋 斠(!K'#濮前!JHcy猟夅鸒鳲糆où_馧i-帆nG襦侐∪ \麰wqy{e-肷誹桃'祧竚f8俐艚 I葱t籱6! 导b4Q;烺z撥抙馹4鄎I湚S@Z篷W-<%崴絕a_萸W<*絆'牠曃k鏞彏(7$佛i榫u8: 饿濯殗堳泖/镧,蛝 抭狸I+鑽A娥鰨o>Z鍵29c觞x v 嘯l 笉v0跂 餻?-滚a貂)z(1证8;`4ya},d銻摎悜.趇RzPi6N贕Z0{P
盹P恮dU崸! 孉A幍娃3L＇? F[孕p}6矣K训a7懇o輻媍n?嫓悝q讴/okgqㄨ骩ツ%猕B[甥= I譁v俐U7墨8>鷦1树oko俍bHl郹| 疧痃腦鮙F-&鸏赴紲n嬏6铌@<髱1宻 v蜛|K咃^ak駊\谖闋軮4Xb"}8%^輳>昐艧嬖捓歃5d!*1@塞詭)q@E4騤]糡ds@ 誵U/ m'L烐預 0.$侙 ' {毟@ 氫瘮x科 埰6尫骸d'!pR.x! @:O-膽\W實WUb1R-砹p8攘>5铇摹W<R酩WQ緥K绎5 !祬鎼舐獟z{
蜮 臑!杇/s}>y芣佤隘┚-^綏-e鉭V 釢T
|縉9奆P蒳蜛PFq磣E佅 {帟γら6簘"舘A眝倇渮搾}蚞
铆4)L 鰻 爵+ }xòzvc8#4錅鸭 n'堥F饅R仛 M鄹4b樋У 0專z鐘?E?咡)C鈡薸ビ$鲪畍+粟s苧3+ H[ 丂 y将x薋嘖螋勘M 揱檉}; 罄鑠2k呉3#=鶵悹|溥魴O鯢*\5潿驠厳憺噦3幐蟡メ仔u佘[?堬f!狙y*紂c$<s^苶{g嶴 齢莮
鶪o鋺徍黶X袬ri 葰2:疎蚶> ~5锫4 (镺X>e隌 5╆f忖 蓜
dUPO鸴渮g玘值/鳰-酏#Z褐臾Wi阪&S
$扻錇滣輰v痌.z:c4匑H銑 勓Fi 锧 B:訁 '
!P*Jc
h@&淭S盄 р孭(蹔xR{奬q@
懽 I!
孭GJ7-( R鵣z)郣璃 i躎樛. h婈簟 液/<# 鄎IN鞰(庺Q迉 EPEPEPEPEPSZ枑仌Sck +溦 揗">啶 0()宧x臘薔' 欴返歽$Q!wf8 扞=*阂o洢轲閦m瓖喉嗈$5舍T >聙.)M'zZ AN:9,!&Z撇\糩釩麹0茔茏噟#﹌L微醕峌]臝m铅88鋑>椘s^u痍M7膚 !鹎!桓n-neR蔍rQ' Oj 窮)ぎ9-j峦嬖+▂墏E剳\87+滒齥 O 鴯OＸ齢6`t 7┊V? 膚○龊 ?豖兾> 齸*紈 銦k郹燌餺L惘酅 qp)0筍銟X铪磷G$`>z仧滕SO
H疝繜Cbs?齩4謑臜登窂c< \'蠿?辐. 88胖耠裏'溞R,4閈戱腯=l{齺 聻7嚩嵀 嗑O馉!Lt甠h &智譕搹覑0糷氥s4黪苲~4觿'4艶蚡Zx.豩z孤i挾O汘22鄞]w儙t|gс@
纭≡疦晣k猕顲茶 ";T彘r俱0:齪9隝y饽磹⌒|Dp艄T 滘3 ' $RGJ挪馚]炭鈂g桰晣~x 摸 藊{Y7, !沐8瀧dpy閻
℅輼7嚰Q h赤騁 ?饞 鳩5裃w坲fX#mJ9`)依N4脆匛&3襽
0iB恓P- F)膓M#歸j U<譓$甦髪4駧4荍JQ覓
)i( ＝wQE QE QE QE QE 肊丂?v弓]緎]r摠i襖萙0孕澣(趉Atk↑ }R 臌 }P
8aZcH箕 逿c\熰_3d]嘏
娲碑扛亏H 敉 p9f3鳤@鵒埈2y霌庁躏 瞩;5>>应嗴罵嘎Z×頝Gc佚GVA祋@
iJR)
7<觼Q@ 規碢h
/狘3?笸誆?歕P~E縣 秳( 飦R慖傽 6袩鵨 )>x I僇 E鰗a ,c /侪郜Q "ダ#襽#6鲟c蕪 願 锤魻舅_*?Q鋄1G |姄孭(*缧H餈~鬑"熗($I(h襍螵煥;(a>1N薘rh鎬揗,醇褍@ 绛I)4夹怣 \R驢s@赦橉-倢)罋p(耭.曕選f.沑夃憄R$PJm臁瞲靭q蟸c壑?鉰汊u鼾q @鞛矚O璎T湄脌x鉦莝趢'洢0
絡黯l瑛y敉!觧3蘾Q 蚛虩麥鷉満d哕缬4V6鏇鎂臬哔瞱4
:q8 範
^Q轓h#xi饮 f绍Px韵/嫰D'皎びd
愩# Qs慩怘廖@嘁"揸専j憈fP,橿噏蟎訔J檨岰鋷 抪y 叆]爟恲r)鸷v寔鞡h1ybuR韪r{s涉渢c"DKpq G!N)华踄H6歧詁爗)勅羀h兺 4 c5觟h+[H [~U裍B掩"颁P币丟A@拃
((((((褗)h1GJZc 0}i\P冸J酩- .8隥9隣 鈝量4Y祯遅;啕,况z锘PJ(1K奪( ぅ Z\觝f枦E -いf層(鎸奺 鼕2)碢福4擯襢拪 Z)(孭袸E 8
% 躍丂 -黰鴿} \a }噼誉 0刁灼睙壏旷 W玄}炼 -hk蔕AK磘黹I僃
ZtR鵬I僃
Zz
<呆`褍@ 濮鱁 ZtR`褍@
GN) `騳4sF
鲘)^:襚褍@猶鳗vg┤ 6c±ホ颕僃
8覗泭Nh 4
(R(摻wQE QE QE QE QE ( 袸J(E奀@h%% ?4f汦 p 鍹 雹 g/夁& 匮e 匙y@ \邚|M/剕 瀤偓H理芴类 鐪g$WI\臤E醈n宅u
鹣故苺m釒铀亻鱹嬔4漵>梄厨s釧 竅 K旽鉶急<`7p= 鰞强饑x3M浨嶅k^周,扠*
v尞渷渷鋇0缠iuД莻/SY;x鐝飶攲g x祁磽鳦乽5磐:bCss$~f衫擉(]<绷<
麲沶6z,手7眣S|縶$9任F+B鵁玨逵a翟DE騸,嚈记拃1 髝1苨P镶 + =﹛y%狗觤7钻*勞錞0I绻|v甗>+窗> {{絑wW 夠樺攩苧Le?聽濧M绝歪婭.图:灐mf食轞[o $ \懺儍婿&炳+x阼xk莽聴+>>鹹m朴" 辻厂靤^y/q鸢N&胺7螯檆I黣~e酇绠Q蛅W:M |(&ED 囷UL蜏7 噧泣s孭7峄粒4宗吊琹.~暎蜃,\ 80s娳襹o‰棺綦啚众杧骡X十猊O馽#汄Ox廔鉥趚,g炰42I跺瑛A8`蔄+=弹#耞\c="W 嫋z漣.沯 愍貒歷p!1眮鄴r1^嶀 -7CC葵Y帝鐍鍴鲱芜荆?t趑-畖z馞5负 $Q炱鮂T蓼鬽憣;洜W%q7>噉疬隯娰Z+杭圬濶<9鐐Oj 麿K繀撾Z_買.牰0疏弈膍掳=x￢颬> 餘島忭F荴柭+浕h覊 町醼Rp胄!83'C禹5|>泳X|嘤(W'H<髶鏋糲芭?L_|e釼囅暶B噋P 韾 ':媡O苓[︽[軓&D膽尣~殚灂樋< 氞誒鰈w乍,伢H莘2x*鴊猸耞 跛俚+_頇
醤 (糤q'wA菇
`j:c 鴑衅穅 $粫赩 睬 釒沒s荰8 {_|6 殮剚$P埋阗 暑羈A#兣kxk?<]i=笸q
y<.侱,粈89韼k嶑晠啹馹俐3Z樾翟贬
霶)蝦?u1呀鴬=[N 糏
L洜i蒼n$剉9<濅磮1==蛒嬊饾鋠z蕺斗'槺坉愴2v) 豸5k:45M.沩S铗遑嘶 T鹄 狏街 平Z譊囱t圾Ｙ> 涡奐&齹 呂Fq@ 檕聴~ 鹤垽迎
媺7愦nM黄ON*婞Z#C腜n71 g栛`鴻{ \a }囡 璧癁3~%^ _Ax-~?.'樤&E%% ;4ShQM IIE .isM 慒E6 vEρ@ 歕觪E :歩i
磾P袸K@ 瑁 :(((((袳 b丒 J( Q@Q@ 娘鶕快h 匐划况4Y祯菪Q7V騕蹺 腥92=A*J＋:n仹I╦窇ZZ趋'抙嫢N娱贓厹袒 桍8蕗q8霁沉
占桏G42)W嶦 PA鄪4/垶-髫t漥 畋晧戔g t8 櫕殢寍5暰譼鑕礡覤n葻 wg懫3葼
; >薒v鰫H5申p*缠{DY] O輪[珊`, 沔騭殖勠C媃荽[Y7v*淌@ !2N 溤^1邹下K}ZU2F桏穜+礫vG $@筐宧 ` 欥?7嘻?#螯蘡~躢v8蟎U6-E酐D緐谧+
塜` 艸痑Y瞲偹煤滯', 果0id 樧傑 g懪X 澈駯洴焚te` UF$濴鍞颞 z譍qo
菁桏04)W嶦 PA鄪缂? x︸祠m^;洈]#颇z鄃痖Vゑ弳熪簗 捾氯釭mT摐鹮侽 嚶 o':東伓,偾付釵 =赍茣廾{sak5 阦g彍FG醂Z鲙|1釛蝓}j洲`罫寬瓼A(牥頕:z娦}wH廕]Q鮗訜钶德8狍幖u Wvv扶痥ym
图,辺b6逪 i歄)作+&K3m<0 銥苺;箃:}F-F[ Y/避*eA睈9==M歗焌=迢v6煮]6麎!匭摉 e嶪潸毌k甶澞&↖渳炨%崩;O 珣鳺闼 h:咑
澊枟 ^m*mN=94襔/脉f珈 \禠:61宒帨AW巼4謷稌be砅栁m0(沐^吲~ 蓟[K]J炲沯鋖潸9#褡喖%<霘瑅捨ャ徦yㄣ$ 8 欕儙唨5瞭唔??禧_讽埚%|躢邔 u胿髭眒ч赽^闝頀I碓'蕎$叭<娗馩忢瓇 選徝歷Ⅵ沋Wp2 '儍恾陔:N疆轝i韠4拡＾s嘛on4п酌 毖l騛磸f銣杗I芚搸8 UmO羄织烕R徐nn 驣,=n+P蔄R2鑙h
/鴅 k薶t;嘟埚樢 & py珤xI汣$殀
UL 靴 漁 枙iu 改"X硫1z伬阖S瑋7㈤\Xi柖颐巽h
V=蹔寁'阺Z擯F(>c?忮^ _Ax?﨑林 -k邕屵騌雽? 癄! "N `礒&ih ( ( ( ( ( ( 碢IKI@ E QE Q迠;á ( ( ( ( mQ@Q@Q@Q@ E-羭P 3茮 秊幻\' 鶕靐 匐紶):g圁-KF]R[┶XY81塅 N$$隽鮸VN酷ii璛Gw o ?: 耠=R鱼G冏X秆~袌亚eテTZD订' C3M鴜gＥ~5駯縤0绒Z]B*&Y+凅*" 佄OS^檏鹎炼R贙k∶ 稈a$p岵-,8 佅┇趙偧=缀E啔愗揞鸇bG&L'wOC腚@ %犴G跌 _掁4玭&$#O,溿k<`渀*痘椇o 嘪n陖矠D6F;rF0+菹<>_
9N帶"厶|尬锛s枝葛秼uM~{揟硧蕚r眚/推茑鋵驚 C釁榜 镶U稘薣 9I匳$`尮n1\謦r4x^U兑璴捯)d>c堵 鐊寊^席/饛5&評
/7nA扝鱻8?^当m醈
用蠣力@歕坈{| '抷蝧 駕= 羫_禊6藳7KId普0Y騭渀VM厧扁 嫗*窴mT汵笒+]fG(,Qr辿躅齄 拥-oL疹bf加|铣8rl廃
鐄o劸
瞩塽K1氭g%);╲蜪 吸 疖鷉♀ ]u
馐$ZD鍴f%z 1霨c\睨潰昕触荭诲焦驓e $覌x霁v荢兞 s冺赹昦伴趍琕稅鈱`rz抷'揬畀鹚潞罘uZ{\]堞 J踾郂B c蟌 醫[8鬫:驨衋K]=7捋踿# 曡1N橕迍缤4娠帏#敀&0y垿0膖R跥=rz?罗瘅僊胔>LH頬 OA)?
铓%kbZ曼搎 3囥 I赛:u3駈冟鸒6z疂
剋~M付絼/,賋鉿浞戍糈0k耯 嬨刐嫛a 5!磞8華`uw!1寬q^| >櫓 鑤ey挶+K據;g5♀_嚍馿赸贲w檙螏FF*:兿^>*别m梺糰 .n穂. dㄠ茅&噣缁O=黖l荎捸拧1$ ?x y! > 鴀 把.-\匍噩$審G 鼾 t福慒"# B偺I8'┃PEPEPEP虩夸ま ^2x Ab寚>嗠熐瓁苚)W旷 W进%_h"l稃G摓6寏槧倞\Q@Q@Q@Q@Q@槧( ( ( ( ( ＝wQE QE QE QE QE (
(
(
(
(8?夁& 匮e 匙y\ 娘鶕靐 匐紶+莮6藎 偁熬栁Y睽A" GF=
{徂&'鴈/ 曛:娉z譿~F牀y︶IR豐嶩-料;Nr2_鳠 鵂k殾c侄鰒铲[7< 憫邃瀝q窝 鯊k衳c梅毻蘎M
獑d嶺/;?賙馡Wq颰 汩^痀M龐鉥j椨jqxq岣'掄籇 傢c伕卄儕炵N疰忦?H7z曟烔绰鈊礠4,A'8殛(瑾+缃J: 趴
蒩峄 轺H/7揭褂$*O5D<+2pF~lP臍幊璲朩^ 挥 7S r7 嬝怎畳緘鹫窡翌b椿1n樉q儞鶅]'嚠 鰃氬狍K捹蓭z疩_3x倇肟8癩R/磎:)d陡d轍侍靼z溩G 仛 宻鴌祡E4I霦曷梟]63 G3 鐮籕^S餹[薽K:作v篰″[欅s欵'>悝s阫'鉫彐ｂo
xIn< 鵔*2K4 S,．闱$揇T- 靌詻L髇看茰錯)6褠 '8+済 }Ex棵]oN撆奄榫/譭穐Z?靰n2颢 ?u邻钙p1 Oh((橚3蒍 0 禁4>
瞼J 屵騌雽? 痺鴞 $鰾 疍枈(((((((((Q@))h＝wQE QE QE QE QE (
(
(
(
(8? & 匮e 匙y\鶕?靑 匐綘糤愕淶幙鄘畁蕼 弤k讪:兵[0=柇瓁 X嘚斔amr凎G宯rN0 TMk酅格 讏<;Q?彏[T鋹騳 耔訮)循<=玦W梬:
}~(+G鴊W"箋换悲瑝v挷伒
T>癞V哙[[iBx縌-謀Y,*涷韌9绵獪 估鋀@ j -フ<)↖璡> 1eN9x讓m89 w漪镝M #駁踧砃質9}飳c癞帄 鎩1噗 > 詀粬v謓胰 嫋;F:蝽夕l汘7弽襳箹肧瞓肿;鄬寣G 8#'=u绾略罢&5峳鏨語墸"R籹嵞 H=L骎|)痫昃整O厶琼 g馘鶓匊粠q岝苎@ Ys館 伉}豕謜M 役
2
n鲭捍?醆隬Z0揚赣ボ堉 e2URpr茜妣>嘐 r餩#$譽j桃鵡N+.蛯;决:晝'找5砜+鸎V: 差蝮讳岂熃讕+襤K 創铭F朂■祀榥<'欏.1竎;硿淯o|>}K谋x揅芝5&8D2亐 #伹籮(夕鴒ㄟ鴖Z吁o捱蓐e?%垐ul,!鰝J濧 >_[xSH4:}譁襢尕22磳鴋剺-岀9 廍 pZ?毛慜〖 麰 {u犴鸈/ J?h?鑉 @ 逧x楛4M俘 r郹 )?幄m胯[ @ 軮汃/鴋玱 懒 腟酷-胯[ @ 貳x4-俘 郹 )筐行械/"=矈/鴋x?鑉 K
3郹 (( 貾岍汕蜎0s缫 碪8 刦_ 麰 {}鈉鰢凤岍G"楟 劭$ 懒 腜笛^&h婸?鋆 坂 )嶜E[菃?鲽?鴬 鳅+喷磩L翣藁g; 狒 骼,縣2i怾hqE摻d`1 瀩=鶳碤^U 驴锾_黵慆 挚锾_黵=Z婒燌h
;Z 袷?釥<+ @韐麰 (炸* 醎隷麈/9K 矿岈 邩盔 z澹氵县礱鯅/9K 缏燇楠 吒盔 z錑泖匒#?Y8! 嶵看噿蜦庇5)nN# 鱜霨鋒蟸4 .齄该
鲝騉4 J鵖硐堳弁Z踝瞎搎 @Ｘ 醎W赱O 鑀N$[()23乡@ -% 碤歀EPEPEPEPEPEPEPK欽( ( ＝wQE QE QE QE QE (
(
(
(
(
婈 踄mnbI牂
I尗) 姈 忸~x阓6M%lcM,c騐 ;?滠 黓w4P
{ 晒 C餾繢滂?9? ]聫兙 缮 ?酦x ?9? ] 聹 騬.忴S~ 﨨O 抛uE p筐 @ 鼫 嫞鐎胯 摀 駏軶@ 7) & 忾酧_7? ]璃料HtX #7R鞮g$a诚|撚孯Яげ籭.赇F簵 00荔讙z鷔]羃|=4义$兙+㎏pz|蘂=:TQ xGD""4粩:+g喞${鋥g鑄Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@ 瑁 :(((((袳 QE V~箋zf榰;壤1 凢O@郎髌;謪鸨駀T恦?85钄P卵 膺 j_鳽唪O黋
^塃 y唿- 嵇', 壏 妵坟Z 螅馞?醎x淬控忴ZW唪O糩
^婨 y宵-;嵇'. ￣濛W@ s N夛嬁 収} D髋盔 砧訮 掠 膺 j?醝=駉 5z5玢鈣琴 挽熧 }s轫O冣li
?ut曹}r+舰8S5G^4 罙 猢腻?%x 臰wE p免b燍掽g 倖 猹螎
踆譝HO鴬襯;蓍4臟湞《 慮 QE QE QE QE QE QE Q迠;á ( ( ( ( mQ@Q@Q@ ['鈜陂v =櫡n躚q驃'幘)咘<
9 馯它u驩膍%`C$坡!澩鏘侚譫"$B襓
%U$w 4?墊k翅搞鸩>'P1遡+6$ x濭<岤wu 鯘^香g,m5K踸)旧鏪舙 櫣p蹟 螿X9焀耒餿Z敄zr舊
v芼戀A67訉94髈腛阇佳4
v鰉釹%3I娻+偢 :褴鯚黃甴|;cшs羒<0 `S攠蟛*x ;b=殜虔崥茎ぺN.焯穮d64{i它_都圾冕雓 谵頺[x鈾z破y a:狙^%9 x%t'Pk瑿U紥u粬0 @,a維离j木5i秡鍡母5煌.4髖绉9-\錐 騴t+'Y6夅
玧栔厰菠忬磅
9?玓N牃稄e粊'U=(8齥7^餲圏Oq湻R禄尞>R(徇腛鳲啢猖瘤# 弿7~飚1愤璮隉糑a玘Y琉隫粏 (#2m昒1 g╇止熧躠|I醴寨L褡墸馃勶5"馗+錥.3橷|矩 O?J <9駟mw哦菃炂idh.蒱橝$1優1寠:冝x垂糢┈抝韩磦I#';Nz @ 鉕:'叚訶蒻\柊1X癡幖鸚UeO+_辀亿[$綌"R伻 >滫W慄j餲圁?
C簉羮q▍朡#多# #閇,fO俸塬察A靂hqx$加|^8$*S瀀{饨 镁!狱Q猧诧侺偓FuV 剒稷 y> 輰
瑖ㄉw#婗婓|,兡红z顫玂殁 V`T帔~ AX馧鐿鈰[k coc鶓K(27$`d 3牢Os駬燹)褆Q㈤砵 dDG.U払霐 1q鋑嚶┃=犊鉄\kw6!jF6 y9>慇 3惘坘ぼ uω贠26閉bR 鄃'撣弰礭W膺噓薶KYYW]忚Ez婵<▁矯哺尧轝H缟輪x
踨pH* < f;絆Q嘲郁飫鰱zI畀蠢-訝,2圊霊譠
(絽勾迎aSJ卆M炉a*P搢鹞翅兆?惮&大 W1 fq鶑螐岤'坾Dt-'O腹祰|矘蜛s 爊 緧z^挛-;N侗圐U糑p
>暷xY褶．]C鈲*+K碦$% > gq霱w鬚濣e衭?>矣J磼鎡縄Y# 3鶓匎沎鳤k岖屰6梠粕QP捋須(鹁с鳪P饹/V桋菀揸(婦咥寲
T<C宖醙卬|+
枸yw)笗6嗲 Brs3祐鬚EPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPEPGz(顯( ( ( ( (碤E QE QE p 糢猦i㈣ 傲猭wb) -兆畑%'-l]3勤玧宝A %欢P儉OBwc苷 駖vオ圪贳茧 Ns蒚$i 嚨s楘'臤
[泹#啮陧岛n6锥貦誾(% N郞謤;雡勴5 gO桳*骆辢=尋嵷p汇8膳X柴_噓+疙,u*赕L靻 容'
O 熉糞莀/糞疔KD奙:k紼5HTC RP萐笽炣噻吁O咡叫艆啛oボ坳p猏D鐰
撉999霝h R駷玜袷譈桼
霱<袢應孌靀 m8疈觰#Z2+U本虮鎪栣%贉;I苝#^1環囤ｉ诋/b[2鶌13$N賓閭W$t韀>2氨皈倪 蜖XZi瓂s5等磪cYc&% z
KZ掖dG5;;愥陁1鲕Fjk=N..嗷秥須 堌88`pyW倄P壹A3舲穳碝CZ{Y沤0亟躊F 姢c#摳蹑 聳鐥铭ゥ鑇 閻躨抂D+. 时 u =Q拄 8湓;+$悤F垢H膄掔[襩翳璕 B橆e窫嵜 NGOZ馹 製o 遤毥奯购{h⒒A$Q燭b胜`1,Aol s澂嗈 /'詍P队5嫕?O督萄跠
甁蟾d<{瓻,s聮"╠t9 B+2O鴝 癒痠i{糋鰒紝I隔]刮y W漻Ft繃~5 X}.泼W嫉庰.Z 顜-8 =''摖|;约C2[.6槕,韻无轘倂佄B
z_腛瘋1%/f麂ǚ陡Q笴 俻%,洓F襰搼廫姱=Nm罿蓿o鎦鲻R糉4,U鰸瓘@pI5膢1/嗭 剞闦M姊5排訠G%槑蚋閹y隌孅O鉞.糋i低魆G
d2禬!@'5陃7﹐崴K軬R禃V9'*' 7iLM馃
= -+XU槖H[Ny韂频 蝤k犭鴭R粬 }: ⒀-叨80Xt苝 n筦: z譀诿葰^璦|褉]mnRR狋我qW.n购( 峸<哺UQ闕
鸾j尜糤嚯婪凔fv綎賚轇7DcN猅 Feo銕乏腓n昹V抻蘣L偅q贕9v? {LsE4i$R#凄22!嚚=檑棡G y <'e醎媈
M f酚.錄O1$昪9q笢3 pU-露+銢}L春D7<肢+ 朹浰'oP 搶嶩圉 GV觮媢冈 [(Y,3,j[ g 耥K簐痭e*Ki朎
q$g懬統O龙膇N♀;雥8喾衜>叶戫^pG=x躿猓饄 駱蒋&疱澽捯%硜機)趯#o^绠H稕ほエZY@襄.fX远 蹡 g 渰S_Y遥覇&簈 嫸滵Dw :讑|$鹁櫘鴱舧z綂夼k|V|;櫉q貇R胗5粪o鑧 (馜7v媢﹂殎娐箩欻-&]1*I蕩G Z犯嗞;媦 T8翥隣館儲桗]皞9鉏媙憫AnI雭\7閃毲勵,諭铛{{湷
$茯9鳡熌~%源 xWC瞜ak兔Iv膉
C 认?C一罍3闅/垶[?瘅嚃[L縢檿橺R秪閟岓于袋Q酀邻弲鮹 琽焄兜朤竩3G!!妙'9顷h謮 d 嗚A鶺唜肦尹C駳]捏 `佒肄\M+o楧 c >@;骻L滦!桁韚;G豆H鰫
H<岳 嶯{嶮 {]!e H SQ]堀潨鱎) m#闌8绡歪/岾 ;椱澱-1儙噶'G詟}}t,贷嫿∧14泂嵷5狞=/5糏6鶷比瘠J刃剅樴/蔬‘W脷v煥榫3痧嗩锩陾歨糏1盉J.瓠卐 $>餲囶蓦3i授冐^J觵2汛 銔７j 嗿鐖|O
oX}<[]溱胘尛 旑$滛r唥3_<<>裏犝磾{mW[撿揬魄q彗搮咢?埧u徇喩釅憩跶:胤o+R捚鵛蠈噇F@亨 (( ?$趧+6U堛8旗>骨L绱鉴l;[> 緰蟄侾舘 汨迅8=rP:u 鰚4[繅Aif.咀鏶~J|6聍稪陭(昀}Mx~曕I W覽MCgm`窅沛>m 傥z硄託匣嘊狱c釯~$:ドk稈吸鶑怤AR 榔1炧鄬爖裓O肏8磠冕絭]KH{捫A.wY駜輪 艪 q9$鲈 QE QE QE QE QE QE Q迠;á ( ( ( ( mQ@Q@Q@ W徏 7$觰M"=7_%-{/]嶍 A xc5LG駄KO臣咶M詞{: }4P榐| 逗鴡 鰟嘦K柨鹻岊筧$u趐 髮S?麱馞4=f鸄灿(穝轫1瀀攏稆t$V繈<.佲]7脷^6鲍逨fXu匲顆0# (k任q@ x!氜[X魦+!l愶c/绕>a9獐x肆齄#駉剈KY费顬{+6艪P ┘i O饍踄%灡vqos#{2T OA疗Du}*+{xU哟桑
28鎀P {z +黈醎犏穬ntw舱躃qk 沏q鵍憲c郛0q氳<7ｘ┑轷荒"挹肕扥敞蜭?a ~]E曞荆co{i*薽q嬔晢A鼚O@ 7聼j 瓞鷁=从=阃秜eT( 09V=;謼億=y 鳫>仞?鰡祍斈96
0 亼颹=7?痮!忭怅)u}^mB諨%偐( 亙斄苢烗*瀺L撁舍壄魸"拗!d5U斔$悈)醼Rr舿蜞
z湫; np諴萘p~藀$-聩俶菍虡#鴖 涄穭黦釳?眠邝:DWZ^詰3鵕聛~l矕還0竛{c诣:筐N剑x隗霓
赣鲛賘2槬9#<帴嶯p/xs纶耨l)馯酩 f%坅
紋藃$岓陖鲍螸觸c^h頪P繉D4_涳A鏲tL熐 .N欸0A `Wmk
:笃邹;煼賉媺d([N蜪銮^k牋O匎'o捂 L汍[簜)C憨+;I\钹 齤赤Oiw 囍器W裻痊&硶胜窧劊爮濟曕鹾(贯x{#x柯Z|惪圗ㄩ騈7o橸v蝬 耜入墩5赳櫒輍阝佩籙B%^$F|佊穄
疲 S鉾,"婴9鋴M嶢;CFG慒痈 g'仇o嚨M'荿5辕m|玀J磽蘓2p #爑-罺鷉磚她J鸚仗"qz藞F>o)@@{=y溏(o x沉?誹 槎航喆鍷&I扻澢n'N87-|9銂:o妘措,&赎邑樦"s2懜鐬p0Gブ]蠄臬?賖3輑燥Qし兯c絋N6# r<瑇F锬-[薿╙媼x鄳'-笎@ 怱锇瓱 鴡颋'真xM惊鐾#媍n犁 珵*痿 +鸾q!;个 纹223 <盓 y緯y#E翼醷-h祋┆腀P2<梅嵷溧悒ǖjV u/賕Q诛f[泬 爙2;禱>U鲩陏糈( 栚E#9
屈P5蚲N杨?o亡棬舲厄疼@阹rG 銣
铊;阂麰琢圅n図q琐}蔝>`F爨 g氃鴩烘煟E＂泲mb陂濚!9rph9=<媚>6咇 黭酠>跿7%斢垷nYY圦膆;酁則矣荿!=澲痐<5Ｘ飇鈂=髳@ 衫U雽s烗W舰#頼鍌e≦8#q^M峤#?
汍F襹7o
鏺媦筑;yWv R屷q蟐针碢爄-家帝 才{眼i1H;E
T
抯O嘵 挥>豩Z龗$'庢贆]J籍pJ*每z扈'O嗿柍餋N鹋鶪e琙箽1$洅7 〣A9蹼鞻譤u 餧*鵪S覄 ' g晼'渄3凎k觝*駸5蓆 隁u軞痉衢WK鮲!夈x孺蕙玿吓V洝隇 祂鼹勻F%c芅沩頌 疛<汽B馧忨閦<:j枓乿4+陛讛r=)禬_ }yc.7妉'/ew鲺Y"SB觅rp 射 p<){＿k氼o+6輧-&靍 莙' ~x PEPEPEPEPEPEPGz(顯( ( ( ( (碤E QE QE y锬 闦n梗xO忙瞩f鎦搑谀I `<1?p 姪x冕穸值靏MKv稺 Tpz冏8闍!Z茗釭梘Z^06闐熂 砟嵪m．@2駯忨们罗栫Q冈. 巠⒊%Ec#朡撬P墊7}q鸅槎饝j1薟箚"侗鈒膰玞帊巕擄(籕T捸申k实=6Xh_ <硙娺Gh祭 z絷{撰P峾1c?娹4罪%蛿⒅踴蠒gPX牢2ry溏柴G腳
鴡鲶F譤$0s磻掅\0冥 $醳苧 v 'j $ >制n炣ki>;L>榗閵瑗猁-|3 罨狧娭谥E领] 珦藄 谓沾k/亃嶏乬复撤C吿奬e=X$rqQ:灡? 鵁\脊D觕虼"l睎8%澤R\暨8挠祯&鈡K袱桼鹴2*鍤A*钹\譣▁n竽_;u){&慽7%鉞遖$9闅 ！踻I馩囙 駏稈鞅i搔E,j苛 , 詬邊Q/沫]ni洯[_ 椟愞T珴雺貔O|g5脽3sN觰y鯖kx礤皗|"P彌禣q淲'痻[W锅;GN竇CU諿V査蕂2偈呟糟;壚帑P甼堤?汭娸&%訰樌脠趓:噜鋧k岏O岦A<餘痑)決詄1 7[廛2.骖 苮着M^鴘╔i撍S镽 傩D<ｆ1P(躼<止O \蒭爘!簡蓊e傊9簸-
0'檗;堔'+x栍SKo哕i+ΚF I蜝绌'医I詁4k Nu嗱;堈餡P w怜3馹沫 火鲄g汍]宰靑i鯵?n, '缋e眵;诡糃
藋裚继2U# y*94 >/鴊 嗶#\]嫽].x鼨WA梆* 竩 t~ >#kzU瘖ゑz踈\耭嘕61
;袸
漆彌飥pNEe榭鮗厇u *鉘}U,≮獞傫俇Ac転=棚黕痤熰;J站穋
X?祢<扞0B巼恟9镧v鶱ｂo侘鱲V綿筑!掙K{h參@v , 闣 4水M猥KxZ釳 閳clLbD鶋'8娉<{]娵厉 炙3Z 5X匕鵼fRA s瀱&'9t窉浦鲭Pt"
<截y$<*d紲 隟慊 l/纶j殁+携k咲亴 浵S昨8 m肭裌淖,翟!奾应.殤堑
轅'俻N2}O嫶絶帪 庅目g炾辸矝1控$橫もL'懟诨岶1皤W#g-吋珍鸚=爿Z用|!甹$:l$硤賯朓頖,鴩臹 椻瘋Gc§祹G詆稩 闟伇Q綪X憛 餻{WO岖楹糁Z睢o璱O%級&@蛸羝H 痡^ 靰k○'勨餩劖ttt抏-%抹H$
=擶IE QE QE Cwimj鲎栶躘擅2F<兞鏌 1[A D慍剮4P獖 t vа@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@Q@ 瑁 :((((( z[ 0 D 媅SO a l n g s 埞 埞 0- 鸱 0 z[ 0 D T a h o m a g s 埞 埞 0- 鸱 0 z[ 0 0 D W i n g d i n g s 埞 埞 0- 鸱 0 z[ 0
A .
@ n ? " d d @ @@ `` t 餷 0 % r
! # $ % ' _ 疖 R $ qN謅9襉燓p R $ 浪 藘:q豅韨 ; R $ yT%X{YxY赔pJ辪 y 统 R $ u`需5.仙昕 " F R $ o硊
EJ諒 hQ 0 咥 臕 @ 8
3 簱蚌 蕷;斍 蕷; g 4 [ d [ d z[ 0 揀 p p p @ < 4 d d d d L 0埞 - 8 0 _ _ _ P P T 1 0
p p % Antiarrhythmic drugs
OVERVIEW the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k INTRODUCTION TO THE ARRHYTHMIAS cardiac arrhythmias may cause the heart
(1) to beat too slowly (sinus bradycardia);
(2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter);
(3) to respond to impulses originating from sites other than the SA node;
(4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). P P G ? * Causes of arrhythmias Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization
if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, , v ( Effect of drugs on automaticity Most of the antiarrhythmic agents suppress automaticity
(1) by decreasing the slope of Phase 4 (diastolic) depolarization
(2) by raising the threshold of discharge to a less negative voltage. , # Abnormalities in impulse conduction / Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. 0 Z 0 , Effects of drugs on conduction abnormalities Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. Antiarrhythmic drugs G the antiarrhythmic drugs can modify impulse generation and conduction. . 5
CLASS I ANTIARRHYTHMIC DRUGS $ Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels
Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. , A V
Use-dependence : Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence ; Z ; g
Quinidine Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0
. It also decreases the slope of Phase 4 spontaneous depolarization.
Actions Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity.
Quinidine also prevents reentry arrhythmias H
D % Therapeutic uses in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. t =
7
K Adverse effects A potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole.
At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. b $ A
Procainamide p 1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of Pharmacokinetics c Procainamide is absorbed following oral administration.
Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential.
NAPA is eliminated via the kidney d d 6 - g Adverse effects W procainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients.
Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias.
Central nervious system (CNS) side effects include depression, hallucination and psychosis.
X Z X Z G
P 3 N
Lidocaine Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels.
Class IB drugs are particularly useful in treating ventricular arrhythmias.
Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. Z $ H Actions Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential
lidocaine suppresses arrhythmias caused by abnormal automaticity.
abolishes ventricular reentry. H 5 + " Pharmacokinetics \ Lidocaine is given intravenously because of extensive first-pass transformation by the liver T Adverse effects Lidocaine has a fairly wide toxic-to-therapeutic ratio;
it shows little impairment of left ventricular function,
The CNS effects include drowsiness, slurred speech, confusion, and convulsions;
cardiac arrhythmias may also occur. Z CLASS II ANTIARRHYTHMIC DRUGS $ 3 The Class II agents include the beta-adrenergic antagonists.
These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.
Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 4 4 H { q + Propranolol reduces the incidence of sudden arrhythmic death after myocardial infarction
The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. E ! CLASS III ANTIARRHYTHMIC DRUGS 5 Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells.
prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential.
Instead, they prolong the effective refractory period. 6 6 0 a 7 " # 痨 P 饇 (
餌
C A 1 餚
s * 師 藿h ? " ` 33 洙 33 8 0 _ _ _ P P T 1 0 . ,吳P^噟 痨 p 饇 (
餌
C A 2 i 餚
s * 師 藿h ? " ` 33 洙 33 8 0 _ _ _ P P T 1 0 . ,吳{膮 r n " W 阙 ?
J o # - (
/ 0 0 D A r i a l n g s 埞 埞 0- 鸱 0 z[ 0 D 媅SO a l n g s 埞 埞 0- 鸱 0 z[ 0 D T a h o m a g s 埞 埞 0- 鸱 0 z[ 0 0 D W i n g d i n g s 埞 埞 0- 鸱 0 z[ 0
A .
@ n ? " d d @ @@ `` | 餿 8 & u !
! # $ % ' ) _ 疖 R $ qN謅9襉燓p R $ 浪 藘:q豅韨 ; R $ yT%X{YxY赔pJ辪 y 统 R $ u`需5.仙昕 " F R $ o硊
EJ諒 hQ 0 咥 臕 @ 8
3 簱蚌 蕷;斍 蕷; g 4 [ d [ d z[ 0 揀 p p p @ < 4 d d d d L 0埞 - 8 0 _ _ _ P P T 1 0
p p J' Antiarrhythmic drugs
OVERVIEW the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k INTRODUCTION TO THE ARRHYTHMIAS cardiac arrhythmias may cause the heart
(1) to beat too slowly (sinus bradycardia);
(2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter);
(3) to respond to impulses originating from sites other than the SA node;
(4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). P P G ? * Causes of arrhythmias Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization
if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, , v ( Effect of drugs on automaticity Most of the antiarrhythmic agents suppress automaticity
(1) by decreasing the slope of Phase 4 (diastolic) depolarization
(2) by raising the threshold of discharge to a less negative voltage. , # Abnormalities in impulse conduction / Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. 0 Z 0 , Effects of drugs on conduction abnormalities Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. Antiarrhythmic drugs G the antiarrhythmic drugs can modify impulse generation and conduction. . 5
CLASS I ANTIARRHYTHMIC DRUGS $ Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels
Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. , A V
Use-dependence : Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence ; Z ; g
Quinidine Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0
. It also decreases the slope of Phase 4 spontaneous depolarization.
Actions Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity.
Quinidine also prevents reentry arrhythmias H
D % Therapeutic uses in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. t =
7
K Adverse effects A potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole.
At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. b $ A
Procainamide p 1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of Pharmacokinetics c Procainamide is absorbed following oral administration.
Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential.
NAPA is eliminated via the kidney d d 6 - g Adverse effects W procainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients.
Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias.
Central nervious system (CNS) side effects include depression, hallucination and psychosis.
X Z X Z G
P 3 N
Lidocaine Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels.
Class IB drugs are particularly useful in treating ventricular arrhythmias.
Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. Z $ H Actions Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential
lidocaine suppresses arrhythmias caused by abnormal automaticity.
abolishes ventricular reentry. H 5 + " Pharmacokinetics \ Lidocaine is given intravenously because of extensive first-pass transformation by the liver T Adverse effects Lidocaine has a fairly wide toxic-to-therapeutic ratio;
it shows little impairment of left ventricular function,
The CNS effects include drowsiness, slurred speech, confusion, and convulsions;
cardiac arrhythmias may also occur. Z CLASS II ANTIARRHYTHMIC DRUGS $ 3 The Class II agents include the beta-adrenergic antagonists.
These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.
Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 4 4 H { q + Propranolol reduces the incidence of sudden arrhythmic death after myocardial infarction
The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. E ! CLASS III ANTIARRHYTHMIC DRUGS 5 Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells.
prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential.
Instead, they prolong the effective refractory period. 6 6 0 a 7 " # $ CLASS IV ANTIARRHYTHMIC DRUGS are calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV node . / $
饘 $ (
餽
S 4 0
餽
S
0
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . ,吳04瞢 r $ B
?
嬡 n $ 6 (
/ 0 0 D A r i a l n g s 埞 埞 0- 鸱 0 z[ 0 D 媅SO a l n g s 埞 埞 0- 鸱 0 z[ 0 D T a h o m a g s 埞 埞 0- 鸱 0 z[ 0 0 D W i n g d i n g s 埞 埞 0- 鸱 0 z[ 0
A .
@ n ? " d d @ @@ `` 饻 餪 + &
! # $ % ' ) * + , - . _ 疖 R $ qN謅9襉燓p R $ 浪 藘:q豅韨 ; R $ yT%X{YxY赔pJ辪 y 统 R $ u`需5.仙昕 " F R $ o硊
EJ諒 hQ 0 咥 臕 @ 8
3 簱蚌 蕷;斍 蕷; g 4 [ d [ d z[ 0 揀 p p p @ < 4 d d d d L 0埞 - 8 0 _ _ _ P P T 1 0
p p r0 Antiarrhythmic drugs
OVERVIEW the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k INTRODUCTION TO THE ARRHYTHMIAS cardiac arrhythmias may cause the heart
(1) to beat too slowly (sinus bradycardia);
(2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter);
(3) to respond to impulses originating from sites other than the SA node;
(4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). P P G ? * Causes of arrhythmias Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization
if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, , v ( Effect of drugs on automaticity Most of the antiarrhythmic agents suppress automaticity
(1) by decreasing the slope of Phase 4 (diastolic) depolarization
(2) by raising the threshold of discharge to a less negative voltage. , # Abnormalities in impulse conduction / Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. 0 Z 0 , Effects of drugs on conduction abnormalities Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. Antiarrhythmic drugs G the antiarrhythmic drugs can modify impulse generation and conduction. . 5
CLASS I ANTIARRHYTHMIC DRUGS $ Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels
Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. , A V
Use-dependence : Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence ; Z ; g
Quinidine Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Mechanism of action Quinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0
. It also decreases the slope of Phase 4 spontaneous depolarization.
Actions Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity.
Quinidine also prevents reentry arrhythmias H
D % Therapeutic uses in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. t =
7
K Adverse effects A potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole.
At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. b $ A
Procainamide p 1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of Pharmacokinetics c Procainamide is absorbed following oral administration.
Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential.
NAPA is eliminated via the kidney d d 6 - g Adverse effects W procainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients.
Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias.
Central nervious system (CNS) side effects include depression, hallucination and psychosis.
X Z X Z G
P 3 N
Lidocaine Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels.
Class IB drugs are particularly useful in treating ventricular arrhythmias.
Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. Z $ H Actions Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential
lidocaine suppresses arrhythmias caused by abnormal automaticity.
abolishes ventricular reentry. H 5 + " Pharmacokinetics \ Lidocaine is given intravenously because of extensive first-pass transformation by the liver T Adverse effects Lidocaine has a fairly wide toxic-to-therapeutic ratio;
it shows little impairment of left ventricular function,
The CNS effects include drowsiness, slurred speech, confusion, and convulsions;
cardiac arrhythmias may also occur. Z CLASS II ANTIARRHYTHMIC DRUGS $ 3 The Class II agents include the beta-adrenergic antagonists.
These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility.
Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 4 4 H { q + Propranolol reduces the incidence of sudden arrhythmic death after myocardial infarction
The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. E ! CLASS III ANTIARRHYTHMIC DRUGS 5 Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells.
prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential.
Instead, they prolong the effective refractory period. 6 6 0 a 7 " # $ CLASS IV ANTIARRHYTHMIC DRUGS are calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV node % ! Verapamil and diltiazem . Verapamil shows greater action on the heart than on vascular smooth muscle, whereas nifedipine, a calcium channel-blocker used to treat hypertension exerts a stronger effect on vascular smooth muscle than on the heart. Diltiazem is intermediate in its actions. @ K
} ! & " Actions verapamil and diltiazem, are more effective against the voltage-sensitive channels, causing a decrease in the slow inward current that triggers cardiac contraction
Verapamfl and diltiazem bind only to open, depolarized channels, thus preventing repolarization until the drug dissociates from the channel. These drugs are therefore use-dependent
that is, they block most effectively when the heart is beating rapidly, P d : ' # Therapeutic uses % Verapamil and diltiazem are more effective against atrial than ventricular dysrhythmias. They are useful in treat- ing reentrant supraventricular tachycardia and reducing ventricular rate in atrial flutter and fibrillation.
In addition, these drugs are used to treat hypertension and angina . ` ( $ Pharmacokinetics @ Verapamil and diltiazem are absorbed after oral administration. . ) ) % Adverse effects Verapamil and diltiazem have negative inotropic properties and therefore may be contraindicated in patients with preexisting depressed cardiac function. Both drugs can also cause a decrease in blood pressure caused by peripheral vasodilation. d
$
饘 $ (
餽
S pA 0
餽
S 窪
0
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . -吳餭5 $
饘 $ (
餽
S 9 0
餽
S 腞
0
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . -吳衪鸋 $
饘 $ (
餽
S pTP 0
P
餽
S 竁P
0 P
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . -吳pz{ $
饘 $ (
餽
S &P 0
P
餽
S 魴P
0 P
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . -吳7N $
饘 $ (
餽
S 堙P 0
P
餽
S P
0 P
餒
0 師 藿h ? 33 洙 33 8 0 _ _ _ P P T 1 0 . -吳堲 r % P 岰 笶 錑 J =L % ?
iN ) R o o t E n t r y 崄d汷嗞 ) Q辮D登 P i c t u r e s 6 C u r r e n t U s e r 8 S u m m a r y I n f o r m a t i o n ( C
! " # $ % & ' ( ) * + , . / 0 1 2 3 4 5 6 7 8 9 : ; < = > ? @ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z [ \ ] ^ _ ` a b c d e f g h i j k l m n o p q r s t u v w x y z { | } ~
IC DRUGS
幻灯片 29
幻灯片 30 CLASS IV ANTIARRHYTHMIC DRUGS Verapamil and diltiazem Actions Therapeuti _缿銘N 微软用户 甠o(u7b c uses Pharmacokinetics Adverse effects 已用的字体 演示文稿设计模板 幻灯片标题 $