Effect of amiloride on ischaemia and reperfusion injury in isolated, perfused rat hearts.
The effect of amiloride, a potent inhibitor of Na+/H+ exchange, on ischaemic reperfused rat hearts was studied in order to investigate whether Na+/H+ exchange or Na+/Ca2+ exchange is involved in ischaemia-reperfusion injury, When hearts were pre-ischaemically loaded with 100 microM amiloride, recovery of left ventricular developed pressure was significantly better than in control hearts, whereas recovery of heart rate at 30-min reperfusion was unaffected. Amiloride pretreatment also decreased creatine phosphokinase activity in the coronary effluent and completely abolished occurrence of ventricular arrhythmias during reperfusion. It also inhibited intracellular Na+ accumulation early in reperfusion (within 5 min), whereas in the late stage (from 5 to 30 min), Ca2+ overload was inhibited. The findings suggest that Na+/H+ exchange participates mainly in the early stage of reperfusion injury and the Na+/Ca2+ exchange system, secondary to Na+/H+ exchange, in the late stage. The reduction in post-ischaemic cardiac dysfunction induced by amiloride pretreatment may be attributable to inhibition of the resultant Ca2+ accumulation during reperfusion.
Department of Cardiovascular Surgery, School of Medicine, University of Tokushima, Japan.
M
M
Yoshizumi
T
T
Kitagawa
Y
Y
Masuda
K
K
Horike
Y
Y
Ogawa
Y
Y
Suzuki
T
T
Tamaki
I
I
Katoh
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D004232:Diuretics; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride