Reduction of myocardial damage by cloricromene during ischemia-reperfusion in the rabbit.
We studied the effect of cloricromene on myocardial damage during ischemia and reperfusion. The left anterior descending coronary artery was occluded in 20 rabbits and cloricromene (6.2 micrograms/kg/min) (n = 10) or placebo (n = 10) were continuously infused. After 10 minutes of occlusion, a first biopsy was obtained from the apex. After 30 minutes, the artery was reopened and after 10 minutes a second biopsy was taken. Both samples were used for chemiluminescence and electron microscopy. The group given placebo showed displacement of the ST segment throughout the ischemic period and arrhythmias during reperfusion; while, in the group given cloricromene, there were transient ST segment elevations in 5 animals, which reverted as the infusion was increased. The chemiluminescence values were 7100 +/- 1300 cpm/mg protein and 14900 +/- 2300 (p less than 0.01) for the first and second biopsies of the control group and 5900 +/- 900 and 6100 +/- 900 (NS) for the first and second biopsies of the cloricromene-treated group. In the group given placebo, the second biopsy showed early signs of irreversible myocyte injury and infarction, whereas samples from the group given cloricromene showed a preservation of myocyte architecture. During ischemia, the percentage of normal mitochondria was lower in the placebo group (p less than 0.0001); and, on reperfusion, the percentage of severely damaged mitochondria was increased in the placebo group (p less than 0.0001). The direct addition of cloricromene in vitro to myocardial homogenates did not reduce hydroperoxide-induced chemiluminescence.
Milei
J
J
Section of Experimental Medicine, Hospital Fernandez, University of Buenos Aires.
Llesuy
S
S
Ferreira
R
R
Grana
D
D
Prosdocimi
M
M
Boveris
A
A
D000818:Animals; D002866:Chromonar / Q000031:analogs & derivatives* / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D051379:Mice; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000648:ultrastructure; D010545:Peroxides; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D020122:tert-Butylhydroperoxide; C025945:cloricromen; D002866:Chromonar