ISCHEMIC PRECONDITIONING AND ARRHYTHMOGENESIS IN THE RABBIT HEART - EFFECTS ON EPICARDIUM VERSUS ENDOCARDIUM

The goals of this study were: (1) to determine if preconditioning prot ects against arrhythmias and contractile dysfunction, and if protectio n for these two endpoints occurs in parallel; and (2) to investigate t he anti-arrhythmic action of preconditioning by examining its effect o n electrical activity in epicardium nu endocardium. Mie monitored ECGs , epicardial and endocardial monophasic action potentials (MAP), left- ventricular developed pressure (LVDP) and end-diastolic pressure (EDP) in isolated rabbit hearts. Hearts were subjected to a 30-min test isc hemia and 45 min of reperfusion. Preconditioning cycles (PC) consisted of 1-4 ischemic episodes (5 min each separated by 10 min of reperfusi on) administered 30 min before the test protocol. The test ischemia ca used ventricular fibrillation (VF) in 42% of non-PC hearts. One PC tot ally suppressed VF (0%). The incidence of VF was 30% in 2 PC, 72% in 3 PC and 47% in 4 PC hearts. A large rise in EDP occurred in non-PC and 1 PC hearts, and this rise was prevented by 2, 3 or 4 PC. None of the protocols improved post-ischemic recovery of LVDP or EDP. The test is chemia generated a large dispersion in MAP duration between epicardium and endocardium (39 ms). but this dispersion was markedly reduced aft er 1 PC (14 ms). In conclusion, our results demonstrate that 1 PC comp letely protects against ischemia-induced VF in rabbit hearts, whereas 2 or more PC are required to prevent the ischemia-induced rise in EDP. Thus, preconditioning against arrhythmias and contractile dysfunction does not occur in parallel. Our data also suggest that 1 PC may exert its anti-arrhythmic effect through reduction of the substrate for ree ntrant arrhythmias during ischemia (dispersion of repolarization) via effects on MAP changes in endocardium. (C) 1998 Academic Press