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Cardiovascular Research 1999 43(4):930-938; doi:10.1016/S0008-6363(99)00103-0
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Cardiac transplantation does not effect ischaemia-induced arrhythmias in rats

P. Guo1, M.K. Pugsley2, S.L. Yong and M.J.A. Walker*

Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2l76 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada

* Corresponding author. Tel.: +1-604-822-9531; fax: +1-604-822-9578 mwalker{at}nortran.com

Objective: In many species arrhythmias induced by myocardial ischaemia appear to be in part dependent upon cardiac sympathetic nerves. However, previous experiments in rats did not suggest that myocardial or other catecholamines are involved in ischaemic arrhythmogenesis in this species. The aim of this study was to investigate this further using transplanted hearts. Methods: We transplanted ’donated’ hearts onto the abdominal aorta of recipient rats and, at varying periods after transplantation, subjected donated and recipient hearts to occlusion of the left anterior descending (LAD) coronary artery. Donated and recipient hearts were tested at various times after transplantation for responsiveness to drugs acting upon aspects of the autonomic nervous system. The intention of this latter study was to assess the status of innervation and receptors simultaneously in both donated and recipient hearts. Results: Donated (transplanted) hearts showed responses consistent with denervation and receptor supersensitivity. Changes varied with the duration of the transplant. Over the same period recipient hearts did not change in responsiveness to drugs. When subjected to coronary artery occlusion, transplanted hearts responded to occlusion with the same frequency and severity of arrhythmias as recipient and other control hearts, regardless of the duration of transplant, or sensitivity to drugs. Conclusions: The results of these experiments suggest that cardiac innervation is not an important factor in the genesis of ischaemia-induced arrhythmias in rats.

KEYWORDS Heart transplant; Coronary occlusion; Ischaemic arrhythmias; Autonomic drugs; Cardiac innervation

1 Department of Pharmacology, Amgen Co., Thousand Oaks, CA, 91320, USA.

2 Department of Pharmacology and Toxicology, XOMA Ltd., Berkeley, CA, 94710, USA.


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