Negroni Jorge A, Lascano Elena C, del Valle Héctor F, Crottogini Alberto J
Department of Physiology, Pharmacology and Biochemistry, Favaloro University, Buenos Aires, Argentinia.
Basic Res Cardiol. 2002 Jan;97(1):55-64. doi: 10.1007/s395-002-8388-7.
Although late preconditioning protects against stunning following several short periods of ischemia-reperfusion, it is not clear if it confers protection against stunning and malignant arrhythmias after a sustained reversible ischemia, and whether KATP channels are involved as triggers and/or end effectors of the protective mechanism. The purpose of this work was thus to test these issues in conscious sheep.
Five groups were considered: CONT (control): the animals were submitted to 12 min ischemia followed by 2 h reperfusion; SWOP (late preconditioning): on the first day, the animals were preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the 12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the preconditioning stimulus.
Percent reperfusion recovery of wall thickening fraction (% WTh) showed late preconditioning protection against stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity index (ASI) also demonstrated that late preconditioning protects against malignant arrhythmias at the onset of reperfusion (CONT: 4.87 +/- 1.62 vs SWOP: 1.39 +/- 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning, both against stunning and arrhythmia incidence, when administered either before the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained ischemia (SWOPG2 vs GLI, p < 0.01).
Results indicate that late preconditioning protects against stunning and arrhythmias following a reversible, sustained ischemia in conscious sheep and that KATP channel participation is negligible as triggers and end effectors of both types of protection.
尽管延迟预处理可保护心脏免受多次短暂缺血再灌注后的心肌顿抑，但尚不清楚其是否能在持续性可逆性缺血后对心肌顿抑和恶性心律失常起到保护作用，以及ATP敏感性钾通道（KATP通道）是否作为保护机制的触发因素和/或终效应器参与其中。因此，本研究旨在在清醒绵羊中验证这些问题。
实验分为五组：对照组（CONT）：动物接受12分钟缺血，随后2小时再灌注；延迟预处理组（SWOP）：第一天，动物接受6次5分钟缺血-5分钟再灌注预处理，24小时后接受12分钟缺血，随后2小时再灌注；格列本脲组（GLIB）：与对照组相同，但在12分钟缺血前30分钟静脉注射KATP通道抑制剂格列本脲（0.4mg/kg）；SWOPG2组：与延迟预处理组相同，但在12分钟缺血前注射格列本脲；SWOPG1组：与延迟预处理组相同，但在预处理刺激前注射格列本脲。
心肌增厚分数的再灌注恢复百分比（%WTh）显示，延迟预处理在整个再灌注过程中对心肌顿抑具有保护作用（SWOP组与CONT组相比，p<0.01）。心律失常严重程度指数（ASI）也表明，延迟预处理可在再灌注开始时预防恶性心律失常（CONT组：4.87±1.62 vs SWOP组：1.39±0.93，p<0.01）。当在预处理刺激前（SWOPG1组与CONT组相比，p<0.01）或持续性缺血前（SWOPG2组与GLI组相比，p<0.01）给予格列本脲时，其无法预防预处理对心肌顿抑和心律失常发生率的影响。
结果表明，延迟预处理可保护清醒绵羊在可逆性、持续性缺血后免受心肌顿抑和心律失常的影响，并且KATP通道作为两种保护类型的触发因素和终效应器，其参与程度可忽略不计。
