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Pharmacological preconditioning with the adenosine triphosphate-sensitive potassium channel opener pinacidil
A E Saltman1, I B Krukenkamp, G R Gaudette
1Division of Cardiothoracic Surgery, University Hospital at Stony Brook and the State University of New York, 11794-8191, USA. saltman@surg.som.sunysb.edu
Background:
Ischemic preconditioning (IPC) decreases infarct size after global or regional ischemia. Potassium channel openers also precondition but are subject to dose-limiting vasodilation. We compared the mechanical and electrophysiological effects of ischemic and pharmacological preconditioning in an isolated rabbit heart model.
Methods:
Rabbit hearts were preconditioned with either 10 micromol/L pinacidil alone (P-), 10 micromol/L pinacidil with 10 micromol/L phenylephrine (P+), or two cycles of global ischemia and reperfusion (IPC) before 1 hour of LAD occlusion. Left ventricular pressure, epicardial monophasic action potential duration (APD) and coronary flow were monitored throughout. Infarct size was determined at the end of reperfusion.
Results:
Regional ischemia uniformly decreased APD (p<0.05). During reperfusion, APDs were prolonged beyond preischemic values in all preconditioned groups (p<0.05). P- and P+ reduced the incidence of fibrillation. P- significantly increased coronary flow (+15%, p = 0.001), whereas IPC and P+ did not. However, IPC and P- significantly decreased systolic function (p<0.05) but P+ did not. In addition, IPC depressed diastolic function (p<0.05) but P- and P+ did not. Infarct size was reduced by all methods (p<0.05).
Conclusions:
Pinacidil presents a safe and effective alternative to IPC for preserving the heart during regional ischemia. Its coronary vasodilatory effects are safely and effectively reversed by the addition of phenylephrine.