Probucol reduces myocardial dysfunction during reperfusion after short-term ischemia in rabbit heart.
The effects of probucol, a lipophilic antioxidant, on the myocardial dysfunction (stunning) observed during reperfusion after 15-min ischemia in rabbit heart were studied. Rabbits received food with or without 1% probucol for 3 weeks. They were then anesthetized and prepared for recording of myocardial segment shortening, arterial blood pressure (BP), left ventricular pressure (LVP), rate of development of LVP (dP/dt), and a lead II ECG. Regional myocardial ischemia was produced by acute occlusion of the first marginal branch of the left coronary artery. Myocardial segment shortening was depressed after reperfusion in control rabbits. In comparison, myocardial segment shortening was significantly greater in probucol-treated rabbits than in control rabbits during reperfusion, indicating a beneficial effect. No hemodynamic or ECG changes measured could explain this difference. The number of premature ventricular contractions was reduced in the probucol-treated group, although the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) were not. Concentrations of probucol in serum and heart of five rabbits were 15.0 +/- 1.2 micrograms/ml and 17.5 +/- 2.5 micrograms/g (mean +/- SEM), respectively. Only probucol concentrations in the serum were positively correlated with the improvement in myocardial segment shortening (r = 0.91, p = 0.03). We conclude that a clinically relevant serum concentration of probucol reduces ischemia-induced myocardial stunning in the rabbit.
Dage
R C
RC
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Anderson
B A
BA
Mao
S J
SJ
Koerner
J E
JE
D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011341:Probucol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013610:Tachycardia / Q000188:drug therapy / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000517:prevention & control; D016276:Ventricular Function / Q000187:drug effects
D011341:Probucol