Abstract 10141: The Sodium Calcium Exchange Inhibitor SEA0400 Prevents Myocardial Injury and Enhances Myofimament Sensitivity to Ca2+ when Used as a Cardioplegia Additive
The Na+/Ca2+ exchange inhibitor SEA0400 prevents myocardial injury in models of ischemia and reperfusion. We therefore explored its potential as a cardioplegia additive.
Methods: Studies were performed using hearts and cardiomyocytes isolated from Fisher rats. Hearts perfused on a Langendorff apparatus were arrested with cold crystalloid cardioplegia with (n=7) or without (n=6) SEA0400 (1 μM) then reperfused after 45min of ischemia. Left ventricular (LV) work, reperfusion arrhythmias, Troponin release and mitochondrial morphology were evaluated. In a separate experiment, cardiomyocytes were arrested using cardioplegia solution with (n=10) or without (n=11) SEA0400 (1 μM) and exposed to hypoxia for 45 min followed by reperfusion. Intracellular Ca2+ transients (Systolic — Diastolic Ca2+) and contraction amplitude were measured using Ca2+ sensitive dye and videomicroscopy.
Results: Hearts arrested with cardioplegia containing SEA0400 had better preservation of LV work when compared to controls (171±30 vs. 77±8 mmHg.ml, p=0.01). Duration of arrhythmias during reperfusion was decreased in the SEA0400 group (28±13 vs. 234±129 s, p=0.001). Troponin release was lower (1.3±0.4 vs. 2.3±0.4 ng/mL, p=0.04) and there were more intact mitochondria seen in the SEA0400 group (18±2 vs. 8±2 per μm2, p=0.001). In isolated cardiomyocytes, SEA0400 did not alter intracellular Ca2+ levels or transients during cardioplegic arrest or reperfusion but did increase contraction amplitude during reperfusion consistent with improved myocardial filament sensitivity to Ca2+ (See Figure).
Conclusions: SEA0400 added to cardioplegia prevents myocardial injury and improves recovery of ventricular function in an isolated heart model of cardioplegic arrest. Isolated cell studies indicate that improved recovery of ventricular function may in part be due to enhanced myofilament sensitivity to Ca2+ seen when SEA0400 is added to the cardioplegia solution.
- © 2010 by American Heart Association, Inc.