Combination Therapy in Treatment of Experimental Ischemic Heart Disease – A Preclinical Study

The present study was designed to investigate the role of combined administration of Ramipril and
Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats
were divided into five groups (= 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg),
Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of
global ischemia (5 min of stabilization, 9 min of global ischemia and 12 min of reflow). Combination of
Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of
superoxide dismutase, reduced glutathione, catalase and nitric oxide and decreased the levels of
thiobarbituric acid reactive substances. In addition, the superior protective role of combination of
Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well
preserved myocardial tissue architecture in light microscopy and transmission electron microscopy
analysis studies. The combination was proved to be effective in salvaging the myocardial tissue
against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further
investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels
are needed.