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(Circulation. 2002;105:2309.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Effects of Pinacidil on Electrophysiological Properties of Epicardial Border Zone of Healing Canine Infarcts

Possible Effects of K_ATP Channel Activation

James Coromilas, MD; Constantinos Costeas, MD; Bernard Deruyter, MD; Stephen M. Dillon, PhD; Nicholas S. Peters, MD; Andrew L. Wit, PhD

From the Departments of Pharmacology and Medicine and the Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY.

Correspondence to James Coromilas, MD, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168 St, New York, NY 10032. E-mail jc47{at}columbia.edu

Background— K_ATP channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation.

Methods and Results— Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a K_ATP channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments). In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments).

Conclusions— The response to pinacidil indicates that K_ATP channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.

Key Words: arrhythmia • ischemia • infarction

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