PRECONDITIONING AND REPERFUSION ARRHYTHMIAS IN THE ISOLATED RAT-HEART - TRUE PROTECTION OR TEMPORAL SHIFT IN VULNERABILITY

Objective: 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. Methods: Isolated rat hearts (n = 12 per group) were Langendorff-perfused with whale 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. Results: 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. Conclusions: In isolated blood purfused 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.