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 to analyse on the cellular level the mechanism by which SIN-1C may exert this effect. To simulate ischemia-reperfusion, isolated adult rat cardiomyocytes were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in presence or absence of SIN-1C. Reoxygenation was started when intracellular Ca²⁺ (measured with fura-2) had increased to ≥10^–5 mol/L and pH_i (BCECF) decreased to 6.6. Development of hypercontracture was determined microscopically. In the control group reoxygenation provoked oscillations of cytosolic Ca²⁺ (60.9±9.6 min^–1 at 5 min of reoxygenation) accompanied by development of hypercontracture (to 77.2±3.8% of end-ischemic cell length). When SIN-1C was added upon reoxygenation, Ca²⁺ oscillations were markedly reduced (27.0±4.5 min^–1, p<0.001) and hypercontracture virtually abolished (90.6±2.0% of end-ischemic cell length, p<0.001). SIN-1C did not influence the recovery of pH_i during reoxygenation. The results indicate that SIN-1C protects cardiomyocytes against reoxygenation-induced hypercontracture by its ability to suppress oscillations of intracellular Ca²⁺ during the early phase of reoxygenation. [ABSTRACT FROM AUTHOR]