Background: The Na+/Ca2+ exchange inhibitor SEA0400 prevents myocardial injury in models of global ischemia and reperfusion. We therefore evaluated its potential as a cardioplegia additive. Methods: Isolated rat cardiomyocytes were exposed to hypoxia (45 min) followed by reperfusion. During hypoxia, cells were protected using cardioplegia with (n = 25) or without (n = 24) SEA0400 (1 μM), or were not protected with cardioplegia (hypoxic control, n = 8). Intracellular Ca2+ levels were measured using Ca2+ sensitive dye (fura-2 AM). Isolated rat hearts were arrested using cardioplegia with (n = 7) or without (n = 6) SEA0400 (1 μM) then reperfused after 45 min of ischemia. Left ventricular (LV) function, troponin release, and mitochondrial morphology were evaluated. Results: Cardiomyocytes exposed to hypoxia without cardioplegia had poor survival (13%). Survival was significantly improved when cells were protected with cardioplegia containing SEA0400 (68%, p = 0.009); cardioplegia without SEA0400 was associated with intermediate survival (42%). Cardiomyocytes exposed to hypoxia alone had a rapid increase in intracellular Ca2+ (305 ± 123 nM after 20 minutes of ischemia). Increases in intracellular Ca2+ were reduced in cells arrested with cardioplegia without SEA0400; however cardioplegia containing SEA0400 was associated with the lowest intracellular Ca2+ levels (110 ± 17 vs. 156 ± 42 nM after 45 minutes of ischemia, p = 0.004). Hearts arrested with cardioplegia containing SEA0400 had better recovery of LV work compared to cardioplegia without SEA0400 (23140 ± 2264 vs. 7750 ± 929 mmHg.μl, p = 0.0001). Troponin release during reperfusion was lower (0.6 ± 0.2 vs. 2.4 ± 0.5 ng/mL, p = 0.0026), and there were more intact (41 ± 3 vs. 22 ± 5%, p < 0.005), and fewer disrupted mitochondria (24 ± 2 vs. 33 ± 3%, p < 0.05) in the SEA0400 group. Conclusions: SEA0400 added to cardioplegia limits accumulation of intracellular Ca2+ during ischemic arrest in isolated cardiomyocytes and prevents myocardial injury and improves recovery of LV function in isolated hearts.
- Cardiac function
- Ischemia/reperfusion injury
- Myocardial protection/cardioplegia
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine