Protective effect of dextran sulfate and heparin on adult rat cardiomyocytes damaged by free radicals

Studies in our laboratory have demonstrated that addition of polyanions, heparin or dextran sulfate, to endothelial cell cultures decrease free radical injury. To determine if these polyanions had a similar effect on cardiomyocytes, models of free radical injury were produced in adult rat cardiomyocyte cultures by: (1) addition of hydrogen peroxide; (2) exposure to hypoxia followed by reoxygenation; or (3) exposure to medium conditioned by endothelial cells that were damaged by hypoxia-reoxygenation. All three procedures significantly decreased cell viability as measured by trypan blue exclusion and increased release of enzymes, lactate dehydrogenase and creatine kinase, into cell medium when compared to control cultures. Addition of dextran sulfate or heparin to medium (5 mu g/ml) prior to cell injury significantly increased cell viability and decreased release of enzymes when cells were damaged by the above protocols. Heparin was significantly less protective than dextran sulfate when cells were injured by hydrogen peroxide or hypoxia-reoxygenation but not when conditioned medium from damaged endothelial cells was added to cardiomyocytes. These results indicate that polyanions are protective of cardiomyocytes as well as endothelium. This protective effect may contribute to the beneficial effects of heparin on the cardiovascular system. (C) 1997 Academic Press Limited.