Hydrogen peroxide dose dependent induction of cell death or hypertrophy in cardiomyocytes

Cardiomyocyte hypertrophy and cell death are often observed in the end stages of heart failure. The triggers of these two cellular processes are not known under most pathological conditions. Oxidants are byproducts of aerobic metabolism. The level of oxidants increases as a result of ischemic reperfusion. Using H9C2 and primary cultured neonatal rat cardiomyocytes, we found that a 2-h pulse treatment with H₂O₂ at 250 μM or lower caused activation of DEVD sequence specific caspases. The activity of DEVD-ase peaked with 200 μM H₂O₂ at 24 h. While a fraction of the cells detached and showed nuclear condensation, the majority of the cells (>55%) survived the treatment and appeared to enlarge when cultured for 5 days. These cells showed increases in cell surface area, cell volume, and protein content. With 200 μM H₂O₂, treated cells appeared to be six times bigger in volume and contained three times more protein per cell than untreated cells. The enlarged cells showed enhanced actin stress fibers and disrupted myofibrils. Our data indicate that while H₂O₂ can cause cell death, the surviving cardiomyocytes undergo hypertrophy.