Pinacidil improves contractile function and intracellular calcium handling in isolated cardiac myocytes exposed to simulated cardioplegic arrest.

Abstract

We examined the effects of pinacidil on contractile function and intracellular calcium in isolated rat cardiomyocytes exposed to cardioplegic solution. Rat myocytes were incubated at 24 degrees C for 2 hours in cardioplegic solution with or without pinacidil (50 micromol/L), then they were perfused with Krebs-Henseleit solution with a gas phase of 95% O2/5% CO2 at the same temperature. Contraction and intracellular calcium transients were then measured by video tracking and spectrofluorometry. During 20 minutes of perfusion after 2 hours in cardioplegic solution with pinacidil, (1) the recovery of contractile function was significantly increased in terms of both amplitude of contraction (98.30% +/- 9.90% versus 81.00% +/- 11.25%; p < 0.05) and peak velocity of cell shortening (100.90% +/- 13.79% versus 76.89% +/- 18.14%; p < 0.01) when compared with myocytes in cardioplegic solution without pinacidil; (2) the amplitudes of the intracellular calcium transients evoked by electrical stimulation and caffeine (10 mmol/L) increased by 23.31% to approximately 40.72% and 61.73%, respectively, compared with those in cardioplegic solution without pinacidil; and (3) the decay time of the caffeine-induced intracellular calcium transient decreased by 36.64% +/- 15.10% relative to that measured in cardioplegic solution without pinacidil. The effects induced by supplementing the cardioplegic solution with pinacidil were diminished in the presence of glibenclamide (10 micromol/L). Addition of the adenosine triphosphate-sensitive potassium-channel opener, pinacidil, to a high potassium cardioplegic solution improves recovery of contractile properties and cytosolic calcium in isolated rat cardiac myocytes.