Avkiran M, Ibuki C
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, UK.
Circ Res. 1992 Dec;71(6):1429-40. doi: 10.1161/01.res.71.6.1429.
Rapid washout of extracellular H+ accumulated during preceding ischemia (i.e., the abrupt restoration of extracellular pH) has been implicated as an arrhythmogenic factor during reperfusion. Therefore, we hypothesized that by limiting the rate at which extracellular pH was restored during early reperfusion it should be possible to protect against reperfusion-induced arrhythmias. To test this, we used isolated rat hearts (n = 12 per group) and a novel dual coronary perfusion cannula that permitted the induction of regional ischemia (10 minutes) and the selective reperfusion (8 minutes) of the ischemic zone with modified solutions. We examined the antiarrhythmic efficacy of 1) acidic (pH 6.6) reperfusion with stepwise restoration of extracellular pH to 7.4 (stepped pH) and 2) transient (2-minute) acidic (pH 7.1, 6.8, 6.6, or 6.4) reperfusion with subsequent abrupt restoration of extracellular pH to 7.4. Hearts in two contemporary control groups were reperfused with solution at pH 7.4 throughout. In all groups, 100% of hearts exhibited ventricular tachycardia (VT) on reperfusion. VT degenerated into ventricular fibrillation (VF) in 100% of hearts in the control group but in only 42% of hearts in the stepped-pH group (p < 0.05). In the groups subjected to transient acidic reperfusion, there was a pH-dependent prolongation of VT cycle length (measured at 15 seconds of reperfusion), which was 47.1 +/- 3.9, 51.1 +/- 5.5, 56.0 +/- 1.9, 60.4 +/- 2.8 (p < 0.05), and 68.8 +/- 5.0 (p < 0.05) msec in the pH 7.4 (control), 7.1, 6.8, 6.6, and 6.4 groups, respectively. In these groups, VT degenerated into VF in 92%, 92%, 83%, 42% (p < 0.05), and 33% (p < 0.05) of hearts, respectively. In conclusion, limiting the rate at which extracellular pH is restored during early reperfusion does not affect the rapid induction of VT but inhibits the degeneration of VT into VF and promotes spontaneous reversion to normal sinus rhythm. This is consistent with a major arrhythmogenic role, during uncontrolled reperfusion, for the rapid washout of extracellular H+.
先前缺血期间积累的细胞外H⁺的快速清除（即细胞外pH的突然恢复）被认为是再灌注期间的一个致心律失常因素。因此，我们假设通过限制早期再灌注期间细胞外pH恢复的速率，应该有可能预防再灌注诱导的心律失常。为了验证这一点，我们使用了离体大鼠心脏（每组n = 12）和一种新型双冠状动脉灌注套管，该套管允许诱导局部缺血（10分钟）并用改良溶液对缺血区进行选择性再灌注（8分钟）。我们研究了以下两种情况的抗心律失常效果：1）酸性（pH 6.6）再灌注，细胞外pH逐步恢复至7.4（阶梯式pH）；2）短暂（2分钟）酸性（pH 7.1、6.8、6.6或6.4）再灌注，随后细胞外pH突然恢复至7.4。两个当代对照组的心脏在整个过程中均用pH 7.4的溶液进行再灌注。在所有组中，100%的心脏在再灌注时出现室性心动过速（VT）。对照组100%的心脏VT恶化为心室颤动（VF），而阶梯式pH组仅42%的心脏出现这种情况（p < 0.05）。在接受短暂酸性再灌注的组中，VT周期长度有pH依赖性延长（在再灌注15秒时测量），在pH 7.4（对照组）、7.1、6.8、6.6和6.4组中分别为47.1±3.9、51.1±5.5、56.0±1.9、60.4±2.8（p < 0.05）和68.8±5.0（p < 0.05）毫秒。在这些组中，VT分别在92%、92%、83%、42%（p < 0.05）和33%（p < 0.05）的心脏中恶化为VF。总之，限制早期再灌注期间细胞外pH恢复的速率不会影响VT的快速诱发，但会抑制VT恶化为VF并促进自发恢复为正常窦性心律。这与在无控制的再灌注期间，细胞外H⁺的快速清除起主要致心律失常作用是一致的。
