Lawson C S, Avkiran M, Shattock M J, Coltart D J, Hearse D J
Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, United Kingdom.
Cardiovasc Res. 1993 Dec;27(12):2274-81. doi: 10.1093/cvr/27.12.2274.
The relationship between arrhythmia severity during reperfusion and the duration of preceding ischaemia is bell shaped. Although ischaemic preconditioning can protect against reperfusion induced arrhythmias it is not clear if this is achieved by a true reduction in arrhythmia severity or by a temporal shift in the bell shaped relationship occurring as a consequence of increased ischaemic tolerance.
Isolated rat hearts (n = 12 per group) were Langendorff-perfused with whole blood from a support rat. Regional ischaemia and reperfusion were induced using a ligature around the left main coronary artery. Cardiac rhythm was recorded continuously.
Repeated cycles of preconditioning (5 min ischaemia and 5 min reperfusion) led to a progressive reduction in the incidence of reperfusion induced ventricular fibrillation following 10 minutes of ischaemia (92%, 66%, 42%, and 8% following 0, 1, 2, and 3 cycles respectively). Three cycles of preconditioning reduced the incidence of reperfusion induced ventricular fibrillation after each of 10 (83% to 17%; p < 0.05), 15 (92% to 42%; p < 0.05), 20 (67% to 25%), 30 (33% to 0%), and 40 (25% to 0%) minutes of ischaemia. Preconditioning also led to a reduced incidence of reperfusion induced ventricular tachycardia following 10 minutes of ischaemia (100% to 42%; p < 0.05). There was no evidence of a temporal shift in the bell shaped relationships: peak incidences of reperfusion induced ventricular fibrillation and ventricular tachycardia each occurred after 15 minutes of ischaemia in both control and preconditioned groups.
In isolated blood perfused rat hearts serial preconditioning cycles provide cumulative protection against reperfusion induced ventricular arrhythmias. This protection occurs over a wide range of ischaemic durations without altering the temporal relationship between the duration of ischaemia and arrhythmia severity. This may indicate that antiarrhythmic protection is not a consequence of anti-ischaemic mechanisms.
再灌注期间心律失常的严重程度与先前缺血持续时间之间的关系呈钟形。尽管缺血预处理可预防再灌注诱导的心律失常，但尚不清楚这是通过真正降低心律失常的严重程度实现的，还是由于缺血耐受性增加导致钟形关系的时间偏移所致。
用来自供体大鼠的全血对离体大鼠心脏（每组12只）进行Langendorff灌注。通过环绕左冠状动脉主干放置结扎线诱导局部缺血和再灌注。持续记录心律。
重复的预处理周期（5分钟缺血和5分钟再灌注）导致缺血10分钟后再灌注诱导的心室颤动发生率逐渐降低（分别在0、1、2和3个周期后为92%、66%、42%和8%）。三个预处理周期降低了在10（83%降至17%；p<0.05）、15（92%降至42%；p<0.05）、20（67%降至25%）、30（33%降至0%）和40（25%降至0%）分钟缺血后再灌注诱导的心室颤动发生率。预处理还导致缺血10分钟后再灌注诱导的室性心动过速发生率降低（100%降至42%；p<0.05）。没有证据表明钟形关系存在时间偏移：在对照组和预处理组中，再灌注诱导的心室颤动和室性心动过速的峰值发生率均在缺血15分钟后出现。
在离体血液灌注的大鼠心脏中，连续的预处理周期对再灌注诱导的室性心律失常提供累积保护。这种保护在广泛的缺血持续时间范围内发生，而不改变缺血持续时间与心律失常严重程度之间的时间关系。这可能表明抗心律失常保护不是抗缺血机制的结果。
