Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts.
Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts.
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DOI：
10.1016/j.yjmcc.2011.04.016
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发表时间：
2011-08
影响因子：
5
通讯作者：
Efimov IR
中科院分区：
文献类型：
--
作者：
Fedorov VV;Glukhov AV;Ambrosi CM;Kostecki G;Chang R;Janks D;Schuessler RB;Moazami N;Nichols CG;Efimov IR
本研究比较了ATP调节钾通道（KATP）开放剂二氮嗪和吡那地尔对患病和正常人心房和心室的作用。我们对充血性心力衰竭（CHF，n=8）和无（NF，n=3）或有（INF，n =2）梗塞的非衰竭人类心脏的冠状动脉灌注右（n=11）或左（n=2）后房室自由壁制备物的心内膜进行了光学绘图。我们还分析了NF（n=8）和CHF（n=4）心脏的左心房和心室中KATP靶Kir6.1、Kir6.2、SUR 1和SUR 2的mRNA表达。在CHF和INF心脏中，二氮嗪显著降低心房（−21±3%和−27± 13%，p<0.01）和心室（−28±7%和−28± 4%，p<0.01）的动作电位时程（APD）。二氮嗪对NF心房APD无明显影响（0±5%）。在所有研究的心脏中，吡那地尔显著降低了心房（−46至-80%，p<0.01）和心室（−65至− 93%，p<0.01）的APD。吡那地尔对心房、心室APD的影响均显著高于二氮嗪（p<0.05）。在吡那地尔灌注期间，在所有心房和心室准备中，爆发性起搏诱导了扑动/颤动，主频分别为14.4±6.1 Hz和17.5 ±5.1 Hz。格列本脲（10 μM）终止了这些心律失常，并将APD恢复至对照值。KATP靶点的相对mRNA表达水平与功能观察结果相关。对CHF和/或既往梗死的反应性重构增强了二氮嗪诱导的APD缩短。心房和心室KATP通道的激活增强了致心律失常性，表明这种激活可能有助于缺血心脏的折返性心律失常。
This study compared the effects of ATP-regulated potassium channel (KATP) openers, diazoxide and pinacidil, on diseased and normal human atria and ventricles. We optically mapped the endocardium of coronary-perfused right (n=11) or left (n=2) posterior atrial-ventricular free wall preparations from human hearts with congestive heart failure (CHF, n=8) and non-failing human hearts without (NF, n=3) or with (INF, n=2) infarction. We also analyzed the mRNA expression of the KATP targets Kir6.1, Kir6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts. In both CHF and INF hearts, diazoxide significantly decreased action potential durations (APDs) in atria (by −21±3% and −27±13%, p<0.01) and ventricles (by −28±7% and −28±4%, p<0.01). Diazoxide did not change APD (0±5%) in NF atria. Pinacidil significantly decreased APDs in both atria (−46 to - 80%, p<0.01) and ventricles (−65 to −93%, p<0.01) in all hearts studied. The effect of pinacidil on APD was significantly higher than that of diazoxide in both atria and ventricles of all groups (p<0.05). During pinacidil perfusion, burst pacing induced flutter/fibrillation in all atrial and ventricular preparations with dominant frequencies of 14.4±6.1 Hz and 17.5 ±5.1 Hz, respectively. Glibenclamide (10 μM) terminated these arrhythmias and restored APDs to control values. Relative mRNA expression levels of KATP targets were correlated to functional observations. Remodeling in response to CHF and/or previous infarct potentiated diazoxide-induced APD shortening. The activation of atrial and ventricular KATP channels enhances arrhythmogenicity, suggesting that such activation may contribute to reentrant arrhythmias in ischemic hearts.
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影响因子：
20.1
作者：
Glukhov AV;Fedorov VV;Lou Q;Ravikumar VK;Kalish PW;Schuessler RB;Moazami N;Efimov IR
通讯作者：
Efimov IR
影响因子：
5.5
作者：
Fedorov, Vadim V.;Lozinsky, Ilya T.;Efimov, Igor R.
通讯作者：
Efimov, Igor R.
影响因子：
20.1
作者：
GELBAND, H;BUSH, HL;HOFFMAN, BF
通讯作者：
HOFFMAN, BF
影响因子：
3
作者：
BILLMAN, GE;AVENDANO, CE;BURROUGHS, JM
通讯作者：
BURROUGHS, JM
DOI：
10.1016/s0022-2828(03)00246-3
发表时间：
2003-12-01
影响因子：
5
作者：
Balana, B;Dobrev, D;Ravens, U
通讯作者：
Ravens, U