Effects of Excessive Long-Term Exercise on Cardiac Function and Myocyte Remodeling in Hypertensive Heart Failure Rats

Abstract

Abstract-The long-term effects of exercise on cardiac function and myocyte remodeling in hypertension/progression of heart failure are poorly understood. We investigated whether exercise can attenuate pathological remodeling under hypertensive conditions. Fifteen female Spontaneously Hypertensive Heart Failure rats and 10 control rats were housed with running wheels beginning at 6 months of age. At 22 months of age, heart function of the trained rats was compared with heart function of age-matched sedentary hypertensive and control rats. Heart function was measured using echocardiography and left ventricular catheterization. Cardiac myocytes were isolated to measure cellular dimensions. Fetal gene expression was determined using Western blots. Exercise did not significantly impact myocyte remodeling or ventricular function in control animals. Sedentary hypertensive rats had significant chamber dilatation and cardiac hypertrophy. In exercised hypertensive rats, however, exercise time was excessive and resulted in a 21% increase in left ventricular diastolic dimension (PϽ0.001), a 24% increase in heart to body weight ratio (PϽ0.05), a 27% increase in left ventricular myocyte volume (PϽ0.01), a 13% reduction in ejection fraction (PϽ0.001), and a 22% reduction in fractional shortening (PϽ0.01) compared with sedentary hypertensive rats. Exercise resulted in greater fibrosis and did not prevent activation of the fetal gene program in hypertensive rats. We conclude that excessive exercise, in the untreated hypertensive state can have deleterious effects on cardiac remodeling and may actually accelerate the progression to heart failure. Key Words: hypertension Ⅲ heart failure Ⅲ exercise Ⅲ hypertrophy Ⅲ myocytes Ⅲ voluntary wheel running Ⅲ SHHF R esearch has shown a predictable remodeling of cardiac myocyte shape underlying progression to heart failure (HF). 1 Initially, under hypertensive conditions, there is a marked increase in myocyte cross-sectional area (CSA) whereas cell length remains normal. Between the ages of 6 and 12 months in female spontaneously hypertensive heart failure (SHHF) rats, after a period of compensated hypertrophy, myocyte length begins to increase without further increase in CSA. This excessive addition of sarcomeres in series continues until the development of overt signs of HF at 24 months. 1 In the healthy heart, aerobic exercise training has been shown to increase myocardial mass, left ventricle (LV) chamber dimensions, and stroke volume. 2,3 In LV dysfunction and in HF patients, exercise has been shown to improve exercise tolerance and symptoms. This benefit has traditionally been attributed to peripheral adaptations. More recent studies, however, indicate that beneficial changes may be occurring centrally as well. As in the healthy heart, these adaptations include increased LV wall thickness and LV function 4,5 and enhanced myocardial ␤-adrenergic responsiveness. 6 Recent studies by Iemitsu et al 7 and Emter et al 8 showed that regular exercise training results in reversal of the fetal ge...

Cardiac Effects of Exercise Training in Hypertension

“…While extreme levels of acute and chronic exercise may be deleterious to the heart by increasing apoptosis, �brosis, and ischemic dysfunction [62,113,114], moderate levels of exercise seem protective from cardiac damage. ese animal studies support the American College of Sports Medicine recommendation for encouragement of exercise on most, if not all, days of the week, at moderate intensities, by accumulating 30 minutes or greater of endurance-style physical activity [7].…”

Left ventricular remodeling with exercise in hypertension

“…This hypothesis is based on a small number of studies in rodents, which generally report that apoptosis is attenuated with training (9,15,16,20,39,40), with the caveat that no study to date has examined the impact of exercise training on cardiomyocyte proliferation in the spontaneously hypertensive rat (SHR) model. The importance of these questions is underscored by the recent report by Schultz et al (38), who showed that excessive levels of voluntary wheel running in aging spontaneously hypertensive heart failure rats increased myocardial fibrosis, worsened left ventricular (LV) function, and hastened the progression to heart failure. Thus the purpose of the present study was to determine how exercise training impacts myocardial remodeling in hypertension, specifically examining the relative roles of cardiomyocyte hypertrophy, apoptosis, and proliferation.…”

Low-Intensity Exercise Training Delays Heart Failure and Improves Survival in Female Hypertensive Heart Failure Rats

“…10 In a previous study, chronic low-intensity aerobic exercise training (LIET) initiated during the late phase of compensated left ventricular hypertrophy delayed the onset of decompensated HF and reduced mortality in male SHHF rats. 11 Conversely, Schultz et al 12 reported recently that chronic voluntary wheel running accelerated pathologic left ventricular (LV) remodeling and increased HF mortality in female SHHF rats. This deleterious effect of voluntary exercise was attributed to the excessive volume and/or intensity of exercise achieved by animals in running wheels.…”