Protective effect of amiloride against reperfusion damage as evidenced by inhibition of accumulation of free fatty acids in working rat hearts.

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 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.

• Authors: Y Nasa, A N Hoque, K Ichihara, H Hashizume, Y Abiko
• Journal: Japanese circulation journal (Jpn Circ J) Vol. 61 Issue 12 Pg. 1021-9 (Dec 1997) ISSN: 0047-1828 [Print] Japan
• PMID: 9412867 (Publication Type: Journal Article)

Chemical References

• Diuretics
• Fatty Acids
• Amiloride

Topics

• Amiloride (administration & dosage)
• Animals
• Diuretics (administration & dosage)
• Fatty Acids (metabolism)
• Heart (drug effects, physiopathology)
• Male
• Myocardial Reperfusion Injury (metabolism, physiopathology, prevention & control)
• Rats
• Rats, Sprague-Dawley