Ischemic preconditioning and arrhythmogenesis in the rabbit heart: effects on epicardium versus endocardium.
The goals of this study were: (1) to determine if preconditioning protects against arrhythmias and contractile dysfunction, and if protection for these two endpoints occurs in parallel; and (2) to investigate the anti-arrhythmic action of preconditioning by examining its effect on electrical activity in epicardium v endocardium. We monitored ECGs, epicardial and endocardial monophasic action potentials (MAP), left-ventricular developed presssure (LVDP) and end-diastolic pressure (EDP) in isolated rabbit hearts. Hearts were subjected to a 30-min test ischemia and 45 min of reperfusion. Preconditioning cycles (PC) consisted of 1-4 ischemic episodes (5 min each separated by 10 min of reperfusion) administered 30 min before the test protocol. The test ischemia caused ventricular fibrillation (VF) in 42% of non-PC hearts. One PC totally 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 ischemia generated a large dispersion in MAP duration between epicardium and endocardium (39ms), but this dispersion was markedly reduced after 1 PC (14ms). In conclusion, our results demonstrate that 1 PC completely 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 reentrant arrhythmias during ischemia (dispersion of repolarization) via effects on MAP changes in endocardium.
St. Boniface General Hospital Research Centre and Dept of Physiology, University of Manitoba, Winnipeg, Manitoba, R2H 2A6, Canada.
M W
MW
Botsford
A
A
Lukas
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D004594:Electrophysiology; D004699:Endocardium / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction; D010496:Pericardium / Q000502:physiology*; D011817:Rabbits