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

Objective: The relationship between arrhythmia severity during reperfu sion and the duration of preceding ischaemia is bell shaped. Although ischaemic preconditioning can protect against reperfusion induced arrh ythmias it is not clear if this is achieved by a true reduction in arr hythmia severity or by a temporal shift in the bell shaped relationshi p occurring as a consequence of increased ischaemic tolerance. Methods : Isolated rat hearts (n = 12 per group) were Langendorff-perfused wit h whale blood from a support rat. Regional ischaemia and reperfusion w ere induced using a ligature around the left main coronary artery. Car diac rhythm was recorded continuously. Results: Repeated cycles of pre conditioning (5 min ischaemia and 5 min reperfusion) led to a progress ive reduction in the incidence of reperfusion induced ventricular fibr illation following 10 minutes of ischaemia (92%, 66%, 42%, and 8% foll owing 0, 1, 2, and 3 cycles respectively). Three cycles of preconditio ning reduced the incidence of reperfusion induced ventricular fibrilla tion 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 ischae mia. Preconditioning also led to a reduced incidence of reperfusion in duced ventricular tachycardia following 10 minutes of ischaemia (100% to 42%; p <0.05). There was no evidence of a temporal shift in the bel l shaped relationships: peak incidences of reperfusion induced ventric ular fibrillation and ventricular tachycardia each occurred after 15 m inutes of ischaemia in both control and preconditioned groups. Conclus ions: In isolated blood purfused rat hearts serial preconditioning cyc les provide cumulative protection against reperfusion induced ventricu lar arrhythmias. This protection occurs over a wide range of ischaemic durations without altering the temporal relationship between the dura tion of ischaemia and arrhythmia severity. This may indicate that anti arrhythmic protection is not a consequence of anti-ischaemic mechanism s.