[Effect of amiloride on the early and late stage of postischemic recovery in isolated perfused rat hearts--possible involvement of Na+/H+ and Na+/Ca2+ exchange].
To investigate whether Na+/H+ exchange or Na+/Ca2+ exchange involves in the ischemic-reperfusion injury, we examined the effect of amiloride, a potent inhibitor of Na+/H+ exchange, on the ischemic reperfused rat heart. When, the hearts were loaded with 0.1 mM amiloride preischemically, the recovery of left ventricular developed pressure was significantly improved than that of the control group, whereas the recovery of heart rate was not influenced by amiloride pretreatment at 30 min of reperfusion. Measurement of intracellular cations revealed that intracellular Na+ accumulation in the early stage (within 5 min) of reperfusion was inhibited by amiloride pretreatment. On the other hand, in the late stage (from 5 min to 30 min) of reperfusion, Ca2+ overload was inhibited by amiloride. These results suggest that Na+/H+ exchange mainly participates in the early stage of reperfusion injury and Na+/Ca2+ exchange system, secondary to the Na+/H+ exchange, participates in the late stage of the reperfusion injury. Moreover, pretreatment with amiloride also decreased creatine phosphokinase activity in the coronary effluent and completely abolished the incidence of ventricular arrhythmia during reperfusion. It is assumed that the improvement of postischemic cardiac dysfunction induced by amiloride pretreatment may be attributable to its inhibition on the resultant Ca2+ accumulation during ischemia.
Department of Cardiovascular Surgery, University of Tokushima, School of Medicine, Japan.
M
M
Yoshizumi
T
T
Kitagawa
Y
Y
Masuda
T
T
Hori
T
T
Kawahito
F
F
Chikugo
Y
Y
Fukuta
I
I
Katoh
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000378:metabolism; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D000252:Calcium-Transporting ATPases; D002118:Calcium