Abstract
To examine whether amiloride protects against ischemia-induced or reperfusion-induced damage to the heart, mechanical and metabolic studies were performed in the isolated, working rat heart. Ischemia decreased both mechanical function and the tissue levels of high-energy phosphates and increased the tissue levels of free fatty acids (FFAs). Reperfusion restored the levels of high-energy phosphates but further increased FFA accumulation. For this reason, accumulation of FFAs was used as an indicator of both ischemia-induced and reperfusion-induced damage. Drugs were added to the perfusion solution 5 min before ischemia until the end of ischemia (pre) or until 10 min after reperfusion (pre+post). Diltiazem (1 or 5 μmol/L pre) decreased the mechanical function of the non-ischemic heart and attenuated both ischemia-induced and reperfusion-induced accumulation of FFAs. Amiloride (50 μmol/L pre) did not affect the mechanical function of the non-ischemic heart or attenuate ischemia-induced or reperfusion-induced FFA accumulation effectively. However, amiloride (50 μmol/L pre+post) did markedly attenuate the reperfusion-induced accumulation of FFAs. In conclusion, diltiazem attenuates both ischemia-induced and reperfusion-induced myocardial damage, probably through its energy-sparing effect as a result of a decrease in mechanical function before ischemia. In contrast, amiloride attenuates only the reperfusion-induced myocardial damage through mechanisms other than the energy-sparing effect. (Jpn Circ J 1997; 61: 1021 - 1029)
