Rozanski G J, Witt R C
Department of Physiology, University of Nebraska College of Medicine, Omaha 68189-4575.
Circulation. 1991 Apr;83(4):1352-60. doi: 10.1161/01.cir.83.4.1352.
The mechanisms underlying repetitive activity during reperfusion of ischemic myocardium are thought to include triggered responses elicited at short pacing cycle lengths. The potential to generate repetitive responses at longer pacing cycle lengths under similar conditions, however, has not been explored. Thus, the present study examined the role of cycle length on the cellular electrical changes produced during recovery from ischemic-like conditions and identified the major component precipitating nondriven, repetitive activity.
Transmembrane potentials were recorded in vitro from isolated rabbit Purkinje fibers exposed to hypoxia (defined as PO2 less than 30 mm Hg, high [K+]o, and zero glucose) plus lactic acidosis (pH 6.7) for 45 minutes and during recovery in normal Tyrode's solution (pH 7.4). Compared with control, action potential duration (90% repolarization) during recovery increased transiently by 40.9 +/- 11.8 and 241.0 +/- 51.1 msec at respective basic cycle lengths of 1,000 and 3,000 msec (both p less than 0.005). In 81% of preparations, action potential prolongation was accompanied by early afterdepolarizations and triggered activity generated from low (positive to -40 mV) or high (negative to -40 mV) membrane potentials. In 62% of experiments, brief periods of abnormal automaticity also occurred. Triggered responses were 1) unaffected by 1 microM ryanodine, 2) abolished by pacing at short basic cycle lengths or by exposing tissues to 2.5 micrograms/ml lidocaine, and 3) more easily induced at long basic cycle lengths or by superfusing 2.5 micrograms/ml quinidine. When tissues were conditioned with hypoxia alone (pH 7.4), action potential prolongation on recovery was comparatively small, and nondriven responses did not develop. Conversely, addition of 10-20 microM amiloride to the hypoxic, acidic test solution augmented recovery-induced action potential prolongation.
We conclude that acidosis, as a component of ischemia, plus slow pacing frequencies may mediate the genesis of early afterdepolarizations and triggered activity in Purkinje fibers on recovery, long after extracellular pH has been restored to normal. These data may have clinical relevance to the mechanisms of reperfusion arrhythmias in the intact human heart.
缺血心肌再灌注期间重复性活动的潜在机制被认为包括在短起搏周期长度时引发的反应。然而，在相似条件下较长起搏周期长度时产生重复性反应的可能性尚未得到研究。因此，本研究探讨了周期长度对从类缺血状态恢复过程中细胞电变化的作用，并确定了引发非驱动性重复性活动的主要成分。
在体外记录分离的兔浦肯野纤维的跨膜电位，这些纤维暴露于缺氧（定义为氧分压小于30mmHg、高细胞外钾离子浓度和零葡萄糖）加乳酸性酸中毒（pH 6.7）45分钟，并在正常台氏液（pH 7.4）中恢复期间进行记录。与对照相比，在恢复期间，当基础周期长度分别为1000和3000毫秒时，动作电位时程（90%复极化）分别短暂增加40.9±11.8和241.0±51.1毫秒（两者p均小于0.005）。在81%的标本中，动作电位延长伴有早期后除极以及由低（正向至-40mV）或高（负向至-40mV）膜电位产生的触发活动。在62%的实验中，还出现了短暂的异常自律性。触发反应具有以下特点：1）不受1μM雷诺丁影响；2）通过短基础周期长度起搏或使组织暴露于2.5μg/ml利多卡因可消除；3）在长基础周期长度时或通过灌流2.5μg/ml奎尼丁更容易诱导产生。当组织仅用缺氧（pH 7.4）处理时，恢复时动作电位延长相对较小，且未出现非驱动性反应。相反，向缺氧酸性测试溶液中添加10 - 20μM阿米洛利可增强恢复诱导的动作电位延长。
我们得出结论，酸中毒作为缺血的一个组成部分，加上缓慢的起搏频率，可能在细胞外pH恢复正常很久之后，介导浦肯野纤维恢复时早期后除极和触发活动的发生。这些数据可能与完整人体心脏再灌注心律失常的机制具有临床相关性。
