Protective effect of amiloride against reperfusion damage as evidenced by inhibition of accumulation of free fatty acids in working rat hearts.
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 mumol/L pre) decreased the mechanical function of the non-ischemic heart and attenuated both ischemia-induced and reperfusion-induced accumulation of FFAs. Amiloride (50 mumol/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 mumol/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.
Nasa
Y
Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Hoque
A N
AN
Ichihara
K
K
Hashizume
H
H
Abiko
Y
Y
D000584:Amiloride / Q000008:administration & dosage*; D000818:Animals; D004232:Diuretics / Q000008:administration & dosage*; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004232:Diuretics; D005227:Fatty Acids; D000584:Amiloride