Hydrogen peroxide as a tool for studying oxidative stress in the heart

RESUMO

Hydrogen peroxide (H2O2) was observed to depolarize the frog sartorius muscle and promote rhythmic contraction of frog cardiac ventricular rings or their contracture. This last effect was sodium-dependent. H2O2 perfused or injected into the aorta of the isolated rat heart induces a positive inotropic effect (with cardiac arrhythmias such as extrasystolic potentiations) followed by deoression of contractility or cardiac contractures, according to the dose employed. The last effects is similar to the "stone heart"observed in the reperfusion injury and may be ascribed to lipoperoxidation (LPO) of the membrane lipids, to protein damage, to reduction in the ATP level and/or to cardioactive compounds liberated by LPO. Besides its direct effect on the ATP level, H2O2 would react with iron ions to produce hydroxyl radicals that attack the cellular membranes. Deferoxamine, an iron chelator and scavenger of hydroxyl radicals, reduced the contractures induced by H2O2. Perfusion with H2O2 increased the LPO of cardiac homogenates measured by chemiluminescence, oxygen uptake and malonaldehyde formation. The fall in ATP levels and the LPO would result in calcium overload of the cardiac fibers and contracture ("stone heart"). The 45Ca uptake was increased by incubation of cardiac strips with H2O2. Previous perfusion of the isolated rat heart with nifedipine or indomethacin reduced the H2O2 cardiac contracture. Vitamin A, a quencher of singlet oxygen liberated during LPO, reduces the H2O2 cardiac contractures and also LPO. Gradual physical exercises, besides increasing the oxygen consumption, protected the heart from oxidative stress. The experimental production of hypothyroidism protected the heart against the H2O2 oxidative stress. The hearts of rats submitted to hypertension with high renin levels showed increased LPO, measured by chemiluminescence and oxygen uptake, indicating that this condition may be produced by oxygen species or causes their production. All these findings give support to the idea that the ischemia-reperfusion injury is an active oxygen species associated disorder that induces cardiac stiffness or contractures that would be produced by calcium overload. Thus, H2O2 may be useful for inducing experimental oxidative stress in the heart and for studying its oxidative status in physiological and pathological situations.