BENEFICIAL EFFECT OF INDAPAMIDE IN EXPERIMENTAL MYOCARDIAL-ISCHEMIA

Indapamide, a nonthiazide chlorosulfamoyl diuretic, which possesses well-known antihypertensive properties, is able to scavenge free radical intermediates involved in lipid peroxidation. In this respect, it has almost the same level of action as alpha-tocopherol. Using an isolated working rat heart preparation, we investigated the effect of indapamide on the myocardial resistance to global total normothermic ischemia followed by reperfusion. The heart, isolated at the end of chronic oral pretreatment (7 day at 3 mg/kg body weight/day), was submitted to ischemia for 15 min and then reperfused. The main results were as follows: in the indapamide-treated group, 1) postischemic recovery of cardiac function was significantly better as compared to the untreated control group; 2) lactate dehydrogenase (LDH) release measured after 15 min of reperfusion was significantly reduced; 3) the myocardial content of organic hydroperoxides (HPO), taken as an index of lipid peroxidation, was significantly lowered, whereas the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) remained unchanged; and 4) electron spin resonance (ESR) analysis of coronary effluents, collected during the first minutes of reperfusion in the presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), revealed a significant modification in the treated group. These findings suggest that indapamide treatment is able to afford some protective effect to cardiac tissue during the early stage of postischemic reperfusion, and that this effect might be related to the antioxidant properties of indapamide.