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Am J Physiol Heart Circ Physiol 278: H2124-H2133, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 6, H2124-H2133, June 2000

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

Masaaki Yashima1,*, Toshihiko Ohara1,*, Ji-Min Cao1, Young-Hoon Kim1, Michael C. Fishbein2, William J. Mandel1, Peng-Sheng Chen1, and Hrayr S. Karagueuzian1

1 Department of Medicine, Division of Cardiology, Cedars-Sinai Research Institute, and 2 Departments of Medicine, and Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, California 90048

The vulnerability of the infarcted hearts to ventricular fibrillation (VF) was tested in in situ canine hearts during nicotine infusion. The activation pattern was mapped with 477 bipolar electrodes in open-chest anesthetized dogs (n = 8) 5-6 wk after permanent occlusion of the left anterior descending coronary artery. Nicotine (129 ± 76 ng/ml) lengthened (P < 0.01) the pacing 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 monophasic action potential (MAP) amplitude and duration (MAPA and MAPD, respectively) alternans in the epicardial border zone (EBZ) but not in the normal zone. With critical reduction of the MAPA and MAPD in the EBZ, conduction block occurred across the long axis of the EBZ cells. Block led immediately to reentry formation in the EBZ with a mean period of 105 ± 10 ms, which, after one to two rotations, degenerated to VF. Nicotine widened the range of diastolic intervals over which the dynamic MAPD restitution curve had a slope >1. We conclude that nicotine facilitates conduction block, reentry, and VF in hearts with healed myocardial infarction by increasing the magnitude of depolarization and repolarization alternans consistent with the restitution hypothesis of vulnerability to VF.

mapping; reentry; conduction block; alternans; action potential restitution

*  M. Yashima and T. Ohara contributed equally to this work.




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