Altered left ventricular remodeling with beta-adrenergic blockade and exercise after coronary reperfusion in rats.
BACKGROUND
beta-Adrenergic blockade is known to improve the survival of patients after acute myocardial infarction and to reduce myocardial infarct size in experimental coronary occlusion. However, the effects of beta-blockade on global and regional left ventricular (LV) remodeling have not been characterized after coronary occlusion with reperfusion. In rats subjected to coronary occlusion and reperfusion, we have demonstrated beneficial effects of reperfusion in sedentary rats with a hypertrophic response to exercise in the surviving outer wall of the infarcted zone, and in this study we investigated whether such remodeling is modified by beta-blockade in both sedentary and exercised rats.


RESULTS
Female Sprague-Dawley rats were randomized into groups at 5 days after 45 minutes of left coronary artery occlusion followed by reperfusion to produce nontransmural infarction. Animals completing the experiment included a propranolol-treated sedentary group (750 mg/l drinking water) (n = 20) and a propranolol-treated exercised group (n = 19), and these groups were compared with two groups of simultaneously randomized rats (which were also part of a separate study): an untreated sedentary group (n = 21) and an untreated exercised group (n = 20). After 3 weeks of intervention, global and regional LV morphological changes were analyzed in 78 completed experiments from midventricular transverse slices of hearts after perfusion fixation. Compared with sedentary untreated rats, propranolol-treated sedentary rats showed significantly increased LV cavity area (41.6 versus 31.5 mm2, p < 0.001) and reduced wall thicknesses in the noninfarcted (1.77 versus 1.95 mm, p < 0.01) and infarcted regions (1.29 versus 1.36 mm, p < 0.01) (two-way ANOVA). In the propranolol-treated rats, exercise further increased the LV cavity area (44.6 versus 39.1 mm2, p < 0.001), reduced the noninfarcted wall thickness (1.62 versus 1.81 mm, p < 0.01), and increased the LV dimension/wall thickness ratio in the noninfarcted region (4.7 versus 3.95 mm, p < 0.001). Whereas exercise in the reperfused group in the absence of beta-blockade significantly increased the viable subepicardial area of the infarcted zone, as reported elsewhere, propranolol treatment prevented this exercise-induced increase of subepicardial area (7.8 rest versus 7.7 mm2 exercise, NS), and there was a significant reduction of total myocardial area in the propranolol-treated exercised group compared with the untreated exercised group (p < 0.05). Corresponding trends in LV weights were not statistically significant.


CONCLUSIONS
These findings provide evidence for altered LV remodeling, including LV cavity dilation and reduced wall thickness, after 3 weeks of propranolol treatment in sedentary rats after coronary artery occlusion and reperfusion to produce nontransmural infarction. In addition, after 3 weeks of exercise together with propranolol treatment, morphological changes were consistent with suppression of exercise-induced myocardial hypertrophy globally and in the viable outer wall of the infarcted region, accompanied by further LV cavity dilation.
Oh
B H
BH
Department of Medicine, University of California San Diego, La Jolla.
Ono
S
S
Gilpin
E
E
Ross
J
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D005082:Physical Exertion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D011433:Propranolol