Sulindac Protects Cardiac Myocytes Against Oxidative Damage
The initial experiments were designed to determine whether sulindac could protect primary neonatal cardiac myocytes in culture against oxidative damage. The cardiac myocytes were exposed to hypoxia and reoxygenation to promote oxidative damage in the presence or absence of sulindac. Cell viability was then assayed by LDH release. Sulindac protection is dose dependent in myocytes exposed to hypoxia/reoxygenation. Sulindac can significantly reduce the level of LDH released following hypoxia/reoxygenation at concentrations as low as 20 μM. As compared to controls, sulindac at 100 μM reduced LDH release, and presumably cell death, by approximately 4-fold. Higher levels of sulindac did not produce a greater effect. Tunel assays (see Materials and Methods) showed that the cell death was due primarily to apoptosis. After hypoxia/reoxygenation, close to 40% of the control cells were tunel positive whereas <5% of the sulindac treated cells were tunel positive.
Based on the cell culture results with cardiac myocytes, studies were initiated to test the effect of sulindac in the intact heart using the Langendorff model.