Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction

The vulnerability of the infarcted hearts to ventricular fibrillation (VF) was tested in in situ canine hearts during nicotine infusion. The activatio n pattern was mapped with 477 bipolar electrodes in open-chest anesthetized dogs (n = 8) 5-6 wk after permanent occlusion of the left anterior descend ing coronary artery. Nicotine (129 +/- 76 ng/ml) lengthened (P< 0.01) the p acing cycle length at which VF was induced from 171 +/- 8.9 to 210 +/- 14.7 ms. Nicotine selectively amplified the magnitude of conduction time and mo nophasic action potential (MAP) amplitude and duration (MAPA and MAPD, resp ectively) alternans in the epicardial border zone (EBZ) but not in the norm al zone. With critical reduction of the MAPA and MAPD in the EBZ, conductio n block occurred across the long axis of the EBZ cells. Block led immediate ly to reentry formation in the EBZ with a mean period of 105 +/- 10 ms, whi ch, after one to two rotations, degenerated to VF. Nicotine widened the ran ge of diastolic intervals over which the dynamic MAPD restitution curve had a slope >1. We conclude that nicotine facilitates conduction block, reentr y, and VF in hearts with healed myocardial infarction by increasing the mag nitude of depolarization and repolarization alternans consistent with the r estitution hypothesis of vulnerability to VF.