Prolonged donor hearts preservation with pinacidil: the role of mitochondria anti mitochondrial adenosine triphosphate-sensitive potassium channels

Abstract

Objective To investigate the effects of pinacidil on isolated rat hearts preservation,and evaluate the roles of myocardial mitochondrial KATP channel (mitoKATP) and the effects on mitochondria. Methods 120 SD rats were randomly divided into five groups (n = 24, 8 at every moment of stabilization,storage and reperfusion) as follows: (1) the group of HTK solution as the control group,(2) the group of HTK solution containing pinacidil (the Pi group), (3) the group of HTK solution containing pinacidil and 5-hydroxydecanote (5HD, a selective mitochondrial KATP channel blocker, the 5HD group), (4) the group of HTK solution containing pinacidil, Hoechst-Marion-Roussel 1098 (HMR1098, a selective sarcolemmal KATP channel blocker, the 1098 group),and (5) the group of HTK solution containing pinacidil, 5HD and HMR1098 (the 5HD + 1098 group). The Langendorff perfusion models were established. All hearts were arrested with the above-mentioned five preservation solutions in a Langendorff apparatus respectively and subsequently dipped into the same solution for 8 h at 4 ℃ followed by 60 min of reperfusion. The hemodynamics,mitochondrial respiratory function,ATP levels,cardiac troponin Ⅰ release and myocardial uttrastructure were examined. Results Compared with the other groups, heart performance parameters, mitochondria]respiratory enzyme activity and myocardial ATP contents in the Pi group were significantly improved as well as the myocardial mitochondria Flameng score. The protection was almost abolished by the addition of 5HD and moderately decreased by HMR1098. Conclusion Pinacidil may further improve the myocardial protection efficacy of donor heart preservation. Energy status preservation is one of important mechanisms of pinacidil and the effect depends more on mitochondrial than on sarcolemmal potassium adenosine triphosphate channels. Key words: Pinacidil; Potassium channels; Heart; Organ preservation