Protection of isolated cardiomyocytes against reoxygenation-induced hypercontracture by SIN-1C

Previous studies have shown that SIN-1C (N-morpholinoiminoacetonitrile) can protect ischemic-reperfused myocardium. The aim of the present study was t o analyse on the cellular level the mechanism by which SIN-1C may exert thi s effect. To simulate ischemia-reperfusion, isolated adult rat cardiomyocyt es were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in pres ence or absence of SIN-1C. Reoxygenation was started when intracellular Ca2 + (measured with fura-2) had increased to greater than or equal to 10(-5) m ol/L and pH(i) (BCECF) decreased to 6.6. Development of hypercontracture wa s determined microscopically. In the control group reoxygenation provoked o scillations of cytosolic Ca2+ (60.9 +/- 9.6 min(-1) at 5 min of reoxygenati on) accompanied by development of hypercontracture (to 77.2 +/- 3.8 % of en d-ischemic cell length). When SIN-1C was added upon reoxygenation, Ca2+ osc illations were markedly reduced (27.0 +/- 4.5 min(-1), p < 0.001) and hyper contracture virtually abolished (90.6 +/- 2.0 % of end-ischemic cell length , p < 0.001). SLN-1C did not influence the recovery of pH, during reoxygena tion. The results indicate that SIN-1C protects cardiomyocytes against reox ygenation-induced hypercontracture by its ability to suppress oscillations of intracellular Ca2+ during the early phase of reoxygenation.