Sensitivity to ischemia of chronically infarcted rat hearts; effects of long-term captopril treatment.
Myocardial infarction induced hypertrophy of non-infarcted myocardium, in parallel with interstitial and perivascular fibrosis and a decreased capillary density, could increase sensitivity to ischemia. The structural cardiac changes can be reversed by long-term captopril treatment. In the present study, ischemic sensitivity in relation to cardiac perfusion was studied in isolated, perfused hearts of untreated and captopril-treated infarcted rats. In chronically (8 weeks) infarcted hearts, maximal vasodilation in response to administered adenosine and nitroprusside, as well as to endogenously released vasodilators during reperfusion, was decreased, suggesting impaired cardiac perfusion. Ischemic release of purines and lactate was reduced in infarcted hearts, indicating decreased sensitivity to ischemia of the remodeled myocardium. Captopril treatment (3-8 weeks post myocardial infarction), which reversed hypertrophy without affecting the flow capacity of the coronary vascular bed, restored maximal cardiac perfusion. Ischemic ATP breakdown was not affected by captopril, whereas lactate release was even further reduced, suggesting alterations towards a more aerobic ATP production. These data indicate that despite the reduced maximal cardiac perfusion, the remodeled myocardium of infarcted hearts is less sensitive to ischemia. Reversal of hypertrophy by chronic captopril restored maximal cardiac perfusion and led to a better preservation of aerobic ATP production during ischemia.
Kalkman
E A
EA
Department of Pharmacology, Erasmus University Rotterdam, Netherlands.
Saxena
P R
PR
Schoemaker
R G
RG
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D002216:Captopril; D000241:Adenosine