Differential effects of glyburide on premature beats and ventricular tachycardia in an isolated tissue model of ischemia and reperfusion.
Differential effects of glyburide on premature beats and ventricular tachycardia in an isolated tissue model of ischemia and reperfusion.
复制标题
在缺血和再灌注的离体组织模型中，格列本脲对早搏和室性心动过速的不同作用。
DOI：
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发表时间：
1992
影响因子：
3.5
通讯作者：
G. Ferrier
中科院分区：
文献类型：
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作者：
J. S. Pasnani;G. Ferrier
在一个分离的组织再灌注模型中，评估了三磷酸腺苷敏感的钾通道阻滞剂格列本脲可能的抗和致心律失常作用。用微电极记录豚鼠右室游离壁心内膜、心外膜或乳头肌两个部位的跨膜电活动。用放置在组织浴两端的两个电极记录心电图。对心内膜进行常规刺激。组织暴露于模拟缺血15min，然后用正常泰氏液再灌流。50%的游离壁在再灌注早期出现快速持续性或非持续性室性心动过速、二联性或三联性室性心动过速并伴有跨壁折返的特点。20%的患者出现以振荡后电位(延迟后除极)为特征的触发性心律失常。心律失常伴跨壁传导时间延长，心内膜有效不应期和动作电位时程缩短。格列本脲(3或30微米)可显著缩短缺血和再灌流早期的动作电位时程和有效不应期。格列本脲不能改变心内膜和跨室壁传导时间；然而，在缺血状态下，格列本脲显著降低了跨壁传导阻滞的发生率。格列本脲可抑制再灌注性心律失常，表现为折返性心律失常，但增强乳头肌振荡性后电位，触发游离壁振荡性后电位心律失常。格列本脲在缺血液、缺血和再灌注液中的作用相同，但仅在再灌注液中出现的格列本脲不起作用。我们的研究表明，在晚期早搏、快速性心律失常和紧密耦合的早搏中，同时具有促心律失常和抗心律失常药物作用的可能的细胞机制。
Possible anti- and proarrhythmic effects of glyburide, an ATP-sensitive K+ channel blocker, were assessed in an isolated tissue model of reperfusion. Transmembrane electrical activity was recorded from endo- and epicardium of isolated segments of guinea pig right ventricular free walls, or two sites on papillary muscles with microelectrodes. An electrocardiogram was recorded by two electrodes placed at opposite ends of the tissue bath. Regular stimulation was delivered to endocardium. Tissues were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution. Rapid sustained or nonsustained ventricular tachycardia, bigeminy or trigeminy with characteristics of transmural re-entry occurred early in reperfusion in 50% of free walls. Triggered arrhythmias with characteristics of oscillatory afterpotentials (delayed afterdepolarizations) occurred in 20%. Arrhythmias were accompanied by prolongation of transmural conduction times and abbreviation of endocardial effective refractory periods and action potential durations. Glyburide (3 or 30 microM) significantly attenuated abbreviation of action potential durations and effective refractory periods during ischemic conditions and early reperfusion. Neither endocardial nor transmural conduction times were modified by glyburide; however, glyburide significantly decreased the incidence of transmural conduction block during ischemic conditions. Glyburide abolished reperfusion arrhythmias with characteristics of re-entry, but potentiated oscillatory afterpotentials in papillary muscles and triggered arrhythmias with characteristics of oscillatory afterpotentials in free walls. Identical effects were seen with glyburide present in ischemic solution, or in both ischemic and reperfusion solutions, but no effect was observed with glyburide present only in reperfusion. Our study demonstrates possible cellular mechanisms underlying simultaneous pro- and antiarrhythmic drug effects exerted on late premature beats and rapid arrhythmias and closely coupled premature beats.