Pharmacological preconditioning with the adenosine triphosphate-sensitive potassium channel opener pinacidil.

Abstract

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.

• Authors: A E Saltman, I B Krukenkamp, G R Gaudette, H Horimoto, S Levitsky
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 70 Issue 2 Pg. 595-601 (Aug 2000) ISSN: 0003-4975 [Print] Netherlands
• PMID: 10969686 (Publication Type: Journal Article)

Chemical References

• Vasodilator Agents
• Pinacidil

Topics

• Action Potentials (drug effects)
• Animals
• Coronary Circulation
• Heart (drug effects)
• Ischemic Preconditioning, Myocardial (methods)
• Male
• Pinacidil (pharmacology)
• Rabbits
• Vasodilator Agents (pharmacology)