Effects of pinacidil on electrophysiological properties of epicardial border zone of healing canine infarcts: possible effects of K(ATP) channel activation.
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.


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.
Coromilas
James
J
Department of Pharmacology and the Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. jc47@columbia.edu
Costeas
Constantinos
C
Deruyter
Bernard
B
Dillon
Stephen M
SM
Peters
Nicholas S
NS
Wit
Andrew L
AL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography / Q000379:methods; D004566:Electrodes; D022062:Electrophysiologic Techniques, Cardiac; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D009203:Myocardial Infarction / Q000503:physiopathology*; D020110:Pinacidil / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology*
D005456:Fluorescent Dyes; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil