Favorable left ventricular remodeling following large myocardial infarction by exercise training. Effect on ventricular morphology and gene expression.

Abstract

IntroductionContinued adverse remodeling of myocardium after infarction may lead to progressive ventricular dilation and heart failure. We tested the hypothesis that exercise training in a healed myocardial infarction-dysfunction rat model can favorably modify the adverse effects of ventricular remodeling including attenuation of abnormal myosin gene expression. Sprague-Dawley rats were subjected to either proximal LAD ligation or sham operation. At 5 wk after the operation, animals were randomly assigned to sedentary conditions or 6 wk of graduated swim training, creating four experimental groups: infarct sedentary (IS), infarct exercise (IE), sham sedentary (SS), and sham exercise (SE). At 11 wk all rats were sacrificed and analyzed.Compared to sedentary infarct controls, exercise training attenuated left ventricular (LV) dilation and allowed more hypertrophy of the non infarct wall. The exercisetrained hearts also showed a reduction in the estimated peak wall tension. Northern blot analysis showed an increase in f8-myosin heavy chain expression in the hearts of the sedentary infarction group soon after infarction when compared to sham controls. However, with exercise training, there was a significant attenuation of the I8-myosin heavy chain expression in the myocardium.Exercise training in a model of left ventricular dysfunction after healed myocardial infarction can improve the adverse remodeling process by attenuating ventricular dilation and reducing wall tension. The abnormal f8-myosin expression was also attenuated in the exercise trained group. This is evidence that abnormal gene expression following severe myocardial infarction dysfunction can be favorably modified by an intervention. (J. Clin. Invest. 1995. 96:858-866 and slower speeds of contraction, and is often a marker of pathological hypertrophy (5-9). Continued late ventricular remodeling along this molecular pathway beyond the period of infarct expansion and scar formation accompanies the transition from ventricular dilation and dysfunction to frank heart failure (2, 10-14). It is known that aerobic exercise training creates a physiologic form of hypertrophy in the myocardium without systolic or diastolic dysfunction (15-18) or abnormal MHC gene expression in animal models (19). It follows that an intriguing possibility exists that suitably timed exercise training post myocardial infarction may overcome the abnormal fetal gene expression and morphological remodeling, and alter the natural course towards heart failure.Exercise training acutely postmyocardial infarction is controversial, as it may aggravate infarct expansion (20)(21)(22). Exercise training in chronic stages of heart failure on the other hand has been shown to improve peripheral metabolism (23, 24) and oxygen consumption (25-27), but its effects on ventricular remodeling are unknown (28).To investigate the effects of exercise training in postmyocardial infarction remodeling, we compared exercise by swim training with sedentary controls in a rat healed infarction model wi...

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

“…Then, in each dietary regimen, mice were assigned randomly to either a physical exercise protocol or to have no lifestyle modifications. Graduated physical exercise consisted of a progressive swimming program in a 1-m 2 surface area tank containing tap water 50 cm in depth and maintained at 23°C according to a protocol originally proposed by Orenstein et al (52). After preliminary pilot experiments (data not shown), to induce a graduated training, on the first day, the swimming time was 10 min in duration, and this time was then increased by 10 min each subsequent day (first week) until the maximum swim duration of 60 min was reached at the end of the second week.…”

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

“…27 With this procedure, we obtained a rat model of AMI, whose mean infarct size was about 40% to 50% of the whole left ventricle ( Figure 2B). In this study, we found that PEDF was normally expressed in cardiomyocytes of LV tissues ( Figure 1C, sham) and that its levels in infarcted areas were decreased after LAD artery ligation ( Figure 1A).…”

“…27 Briefly, male Sprague-Dawley rats (weighting about 300 g at 8 weeks of age; Charles River Breeding Laboratories, Yokohama, Japan) were anesthetized with intraperitoneal injections of ketamine hydrochloride (100 mg/kg b.wt.) and xylazine (5 mg/kg b.wt.).…”

Role of the Exercise Pressor Reflex in Rats With Dilated Cardiomyopathy

“…37,38 In rat models of cardiomyopathy, training has been reported to enhance chronotropic function, reverse detrimental variations in cardiac myosin gene expression and isozyme composition, attenuate ventricular dilation, and diminish wall tension within the heart. 39,40 Increases in oxidative enzyme activity and improvements in exercise-induced metabolic profiles within skeletal muscle have also been described. 41 If effective treatment of EPR dysfunction in heart failure proves a viable therapy for potentiating exercise tolerance, resultant augmentations in exercise capacity would enhance a patient's ability to tolerate physical training, potentially increasing the benefits derived from its prescription.…”