Botsford M W, Lukas A
St. Boniface General Hospital Research Centre and Dept of Physiology, University of Manitoba, Winnipeg, Manitoba, R2H 2A6, Canada.
J Mol Cell Cardiol. 1998 Sep;30(9):1723-33. doi: 10.1006/jmcc.1998.0735.
The goals of this study were: (1) to determine if preconditioning protects against arrhythmias and contractile dysfunction, and if protection for these two endpoints occurs in parallel; and (2) to investigate the anti-arrhythmic action of preconditioning by examining its effect on electrical activity in epicardium v endocardium. We monitored ECGs, epicardial and endocardial monophasic action potentials (MAP), left-ventricular developed presssure (LVDP) and end-diastolic pressure (EDP) in isolated rabbit hearts. Hearts were subjected to a 30-min test ischemia and 45 min of reperfusion. Preconditioning cycles (PC) consisted of 1-4 ischemic episodes (5 min each separated by 10 min of reperfusion) administered 30 min before the test protocol. The test ischemia caused ventricular fibrillation (VF) in 42% of non-PC hearts. One PC totally suppressed VF (0%). The incidence of VF was 30% in 2 PC, 72% in 3 PC and 47% in 4 PC hearts. A large rise in EDP occurred in non-PC and 1 PC hearts, and this rise was prevented by 2, 3 or 4 PC. None of the protocols improved post-ischemic recovery of LVDP or EDP. The test ischemia generated a large dispersion in MAP duration between epicardium and endocardium (39ms), but this dispersion was markedly reduced after 1 PC (14ms). In conclusion, our results demonstrate that 1 PC completely protects against ischemia-induced VF in rabbit hearts, whereas 2 or more PC are required to prevent the ischemia-induced rise in EDP. Thus, preconditioning against arrhythmias and contractile dysfunction does not occur in parallel. Our data also suggest that 1 PC may exert its anti-arrhythmic effect through reduction of the substrate for reentrant arrhythmias during ischemia (dispersion of repolarization) via effects on MAP changes in endocardium.
（1）确定预处理是否能预防心律失常和收缩功能障碍，以及对这两个终点的保护作用是否同时出现；（2）通过研究预处理对心外膜和心内膜电活动的影响来探讨其抗心律失常作用。我们监测了离体兔心的心电图、心外膜和心内膜单相动作电位（MAP）、左心室舒张末压（LVDP）和舒张末压（EDP）。心脏经历30分钟的试验性缺血和45分钟的再灌注。预处理周期（PC）包括在试验方案前30分钟给予1 - 4次缺血发作（每次5分钟，间隔10分钟再灌注）。试验性缺血在42%的非预处理心脏中导致心室颤动（VF）。一次预处理完全抑制了VF（0%）。在2次预处理的心脏中VF发生率为30%，3次预处理为72%，4次预处理为47%。在非预处理和1次预处理的心脏中EDP大幅升高，而2、3或4次预处理可预防这种升高。所有方案均未改善缺血后LVDP或EDP的恢复。试验性缺血在心外膜和心内膜之间产生了较大的MAP持续时间离散度（39毫秒），但在1次预处理后这种离散度明显降低（14毫秒）。总之，我们的结果表明，1次预处理可完全预防兔心缺血诱导的VF，而预防缺血诱导的EDP升高则需要2次或更多次预处理。因此，针对心律失常和收缩功能障碍的预处理并非同时出现。我们的数据还表明，1次预处理可能通过影响心内膜MAP变化，减少缺血期间折返性心律失常的基质（复极离散度）来发挥其抗心律失常作用。
