Cokkinos Alexandros D, Tzeis Stylianos, Moraitis Panagiotis, Pantos Constantinos, Carageorgiou Hariklia, Panousopoulos Dimitrios, Varonos Dennis D, Cokkinos Dennis V
Department of Pharmacology, University of Athens, Athens, Greece;
Exp Clin Cardiol. 2003 Spring;8(1):5-9.
The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice.
To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration.
Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3). Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%).
LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3.
Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart.
缺血预处理(PC)在正常心脏中的有益作用已得到广泛研究,但其对患病心脏的影响仍 largely 未知。尽管在临床实践中经常遇到难以评估的不同间隔的缺血情况,但此前尚未研究过 PC 对已缺血心肌的影响。
研究在不同持续时间的缺血期后应用 PC 时,其心脏保护作用是否得以保留。
本研究使用雄性 Wistar 大鼠。将离体正常大鼠心脏以 Langendorff 模式灌注。在进行 20 分钟零流量全心缺血然后 45 分钟再灌注之前,心脏先经历 20 分钟缺血期然后 10 分钟再灌注(A1 组);先经历 20 分钟缺血期然后 10 分钟再灌注以及两周期 PC(3 分钟缺血、5 分钟再灌注,接着 5 分钟缺血和 5 分钟再灌注)(A2 组);以及两周期 PC 然后是 20 分钟缺血期和 10 分钟再灌注(A3 组)。B 组和 C 组分别先经历 15 分钟和 10 分钟缺血,1、2 和 3 亚组按上述方法处理。在再灌注 45 分钟时测量左心室舒张末期压力(以 mmHg 为单位的 LVEDP45)。缺血后左心室发展压力的恢复以初始值的百分比表示(LVDP%)。
A1 组和 A2 组之间的 LVDP%和 LVEDP45 相似,而当缺血预处理先于两个缺血期(A3 组)时,与 A1 组和 A2 组相比,其 LVDP%显著更高且 LVEDP45 显著更低。与 B1 组相比,B2 组左心室功能恢复未增加。C1、C2 和 C3 组之间的 LVDP%和 LVEDP45 相似。
缺血预处理不能改善最初经历 20 分钟或 15 分钟零流量全心缺血的离体大鼠心脏的功能恢复,而最初 10 分钟的缺血期似乎能对心脏进行预处理。