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.
Botsford
M W
MW
St. Boniface General Hospital Research Centre and Dept of Physiology, University of Manitoba, Winnipeg, Manitoba, R2H 2A6, Canada.
Lukas
A
A
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