Perchenet L, Kreher P
Laboratoire de Neurophysiologie, Université d'Angers, France.
J Cardiovasc Pharmacol. 1995 Nov;26(5):831-40. doi: 10.1097/00005344-199511000-00021.
Changes in action potential duration (APD) were studied during ischemic/reperfusion injury preceded or not by preconditioning in isolated rat hearts. Hearts were perfused on a Langendorff apparatus with Krebs-Henseleit carbonate buffer and submitted to 25-min global low-flow ischemia (coronary flow, 0.3 mol x min-1) followed by 30-min reperfusion. In hearts that had been preconditioned, two intermittent periods of total ischemia for 5 min each, separated by 5-min reflow, were performed before low-flow ischemia. At the end of the ischemic period, APs were significantly prolonged in nonpreconditioned hearts; this prolongation was abolished by preconditioning. Moreover, preconditioning increased the recovery of the contractile function. Therefore, ischemia can widen APD. The results also showed that in rats, preconditioning can be produced in a manner qualitatively similar to preconditioning in other species. Verapamil (3 x 10(-9) mol x min(-1)) or 4-aminopyridine (4-AP, 3 x 10(-6) mol x min(-1)) applied exclusively during low-flow ischemia significantly improved postischemic contractile function in nonpreconditioned hearts (25.9 +/- 4.4. and 37.9 +/- 2.4 vs. 12.9 +/- 5.3%, respectively) as well as in preconditioned hearts (61.8 +/- 4.2 and 55.5 +/- 4.7 vs. 36.0 +/- 1.4%, respectively). With verapamil, this protection was associated with a decrease in APD at 90% of repolarization in the nonpreconditioned hearts (APD90 32.2 +/- 0.1 vs. 71.1 +/- 6.7 ms at the end of ischemia). With 4-AP, this same protection was associated with an increase in APD in the preconditioned hearts (APD90 67.7 +/- 0.7 vs. 48.5 +/- 2.6 ms at the end of ischemia). Both agents given during a 25-min ischemic challenge improved myocardial recovery in nonpreconditioned and preconditioned hearts, despite discordant effects on the AP. Furthermore, the action of these agents was cumulative with the effect of preconditioning.
在离体大鼠心脏中，研究了预处理或未预处理情况下缺血/再灌注损伤期间动作电位持续时间（APD）的变化。心脏在Langendorff装置上用 Krebs-Henseleit 碳酸盐缓冲液灌注，先进行 25 分钟的全心低流量缺血（冠状动脉血流量为 0.3 ml·min-1），然后再灌注 30 分钟。在经过预处理的心脏中，在低流量缺血之前进行两个间歇性的全缺血期，每次 5 分钟，中间间隔 5 分钟的再灌注。在缺血期末，未预处理的心脏中动作电位显著延长；预处理可消除这种延长。此外，预处理可提高收缩功能的恢复。因此，缺血可使 APD 增宽。结果还表明，在大鼠中，预处理的产生方式在质量上与其他物种的预处理相似。仅在低流量缺血期间应用维拉帕米（3×10-9 mol·min-1）或 4-氨基吡啶（4-AP，3×10-6 mol·min-1）可显著改善未预处理心脏（分别为 25.9±4.4 和 37.9±2.4，而对照组为 12.9±5.3%）以及预处理心脏（分别为 61.8±4.2 和 55.5±4.7，而对照组为 36.0±1.4%）缺血后的收缩功能。使用维拉帕米时，这种保护作用与未预处理心脏复极化 90%时 APD 的缩短有关（缺血末期 APD90 为 32.2±0.1 毫秒，而缺血末期为 71.1±6.7 毫秒）。使用 4-AP 时，这种相同的保护作用与预处理心脏中 APD 的增加有关（缺血末期 APD90 为 67.7±0.7 毫秒，而缺血末期为 48.5±2.6 毫秒）。在 25 分钟的缺血挑战期间给予这两种药物，均可改善未预处理和预处理心脏的心肌恢复，尽管它们对动作电位有不同的影响。此外，这些药物的作用与预处理的效果具有累积性。
