Evaluation of the Sodium Calcium Exchange Inhibitor

Abstract

Arresting the heart with cardioplegia solution is the usual strategy to protect the myocardium during cardiac surgery. However, ischemia-reperfusion injury, due in part to Ca2+ overload, remains a clinical problem. Ca2+ influx during ischemia occurs through reverse mode action of the Na+/Ca2+ exchanger. We therefore tested the hypothesis that delivering the Na+/Ca2+ exchanger blocker SEA0400 to a cardioplegia solution would result in superior myocardial protection during ischemic-cardioplegic arrest. Studies were performed on isolated hearts and individual cardiomyocytes from young adult male Fisher Rats. Hearts arrested with cardioplegia containing SEA0400 showed improved recovery of left ventricular function after reperfusion. The onset of reperfusion arrhythmia was delayed, troponin release was reduced, and mitochondrial damage was minimized. In the isolated cell model, contraction amplitudes were higher during reperfusion in the SEA0400 group without a change in Ca2+ transients. This suggests that cells arrested with cardioplegia containing SEA0400 developed improved myofilament sensitivity to Ca2+.