Exercise training in adverse cardiac remodeling

Abstract

Cardiac remodeling in response to a myocardial infarction or chronic pressure-overload is an independent risk factor for the development of heart failure. In contrast, cardiac remodeling produced by regular physical exercise is associated with a decreased risk for heart failure. There is evidence that exercise training has a beneficial effect on disease progression and survival in patients with cardiac remodeling and dysfunction, but concern has also been expressed that exercise training may aggravate pathological remodeling and dysfunction. Here we present studies from our laboratory into the effects of exercise training on pathological cardiac remodeling and dysfunction in mice. The results indicate that even in the presence of a large infarct, exercise training exerts beneficial effects on the heart. These effects were mimicked in part by endothelial nitric oxide synthase (eNOS) overexpression and abrogated by eNOS deficiency, demonstrating the importance of nitric oxide signaling in mediating the cardiac effects of exercise. Exercise prior to a myocardial infarction was also cardioprotective. In contrast, exercise tended to aggravate pathological cardiac remodeling and dysfunction in the setting of pressure-overload produced by an aortic stenosis. These observations emphasize the critical importance of the underlying pathological stimulus for cardiac hypertrophy and remodeling, in determining the effects of exercise training. Future studies are needed to define the influence of exercise type, intensity and duration in different models and severities of pathological cardiac remodeling. Together such studies will aid in optimizing the therapy of exercise training in the setting of cardiovascular disease.

Guiding the failing heart to exercise

“…It is now clear that exercise exerts a number of beneficial effects in CHF, including an improvement of skeletal muscle perfusion, and metabolism, breathing efficiency, and neurohumoral activation [ 1 ]. More recent evidence indicates that exercise training in patients with CHF also improves cardiac function [ 2 ], which is in agreement with observations in animal models of CHF and appears mediated by exercise-induced amelioration of CHF-associated interstitial fibrosis and cardiomyocyte dysfunction and apoptosis [ 3 ]. These beneficial effects of exercise are the consequence of the activation of different molecular signalling pathways that drive the transcriptional control of cardiac remodelling in exercise training versus CHF [ 1 , 3 , 4 ].…”

Exercise Training Has Contrasting Effects in Myocardial Infarction and Pressure Overload Due to Divergent Endothelial Nitric Oxide Synthase Regulation

“…In addition to the stimulation of eNOS, EX beneficially influences the cardiac nitroso–redox balance by activating reactive oxygen species (ROS) scavenger enzymes such as superoxide dismutases (SODs) [ 14 , 15 ]. Accordingly, we and others have demonstrated that EX improves survival and attenuates LV dysfunction, oxidative stress, and fibrosis in a mouse model of myocardial infarction (MI) [ 16 , 17 , 18 , 19 ], and have additionally demonstrated that full eNOS expression is required for these beneficial EX effects after MI [ 20 ].…”

Beneficial Effects of Physical Exercise on Functional Capacity and Skeletal Muscle Oxidative Stress in Rats with Aortic Stenosis‐Induced Heart Failure

“…The influence of exercise during conditions characterized by persistent left ventricular pressure-overload such as aortic stenosis remains unsettled. As life expectancy is increasing and aortic stenosis prevalence augments with age, the number of patients with pressure-overload-induced heart failure will grow [ 17 ]. Experimental studies on the effects of exercise on cardiac and skeletal muscle during aortic stenosis have shown controversial results.…”