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

Abstract

Abstract-Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats. Animals with severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal heart failure or were euthanized because of age-related complications. Exercise delayed mortality resulting from heart failure (PϽ0.001) and all causes (PϽ0.05) and transiently attenuated the systolic hypertension and contractile dysfunction observed in the sedentary animals but had no effect on cardiac morphology or contractile function in end-stage heart failure. Training had no effect on terminal myocardial protein expression of antioxidant enzymes, calcium handling proteins, or myosin heavy chain isoforms but was associated with higher cytochrome oxidase activity in cardiac mitochondria (PϽ0.05) and a greater mitochondrial content of cardiolipin, a phospholipid that is essential for optimal mitochondrial energy metabolism. In conclusion, low-intensity exercise training significantly delays the onset of heart failure and improves survival in female hypertensive heart failure rats without eliciting sustained improvements in blood pressure, cardiac function, or expression of several myocardial proteins associated with the cardiovascular benefits of exercise. The effects of exercise on cytochrome oxidase and cardiolipin provide novel evidence that training may improve prognosis in hypertensive heart disease by preserving mitochondrial energy metabolism. Key Words: exercise Ⅲ heart failure Ⅲ hypertrophy Ⅲ mortality Ⅲ rats D espite long-standing concern over its safety and use in the treatment of heart failure (HF), accumulating evidence suggests that exercise training is a useful adjuvant therapy in stable HF patients, capable of improving functional capacity, attenuating or reversing pathologic remodeling of the heart, and enhancing quality of life. 1,2 Although a lack of physical activity has been associated with poor prognosis in HF patients, 3,4 whether chronic exercise is an effective means of improving survival has not been clearly established. 5 Several studies indicate that exercise training elicits favorable effects on the myocardium in stable HF patients receiving concomitant pharmacotherapy 1,6 and in various animal models of genetic and surgically induced cardiac hypertrophy and failure. 7-9 However, few studies have examined the independent effect of exercise training on disease progression and mortality in a clinically relevant model of hypertensive HF. The spontaneously hypertensive-HF (SHHF) rat represents a well-characterized congenital model of chronic hypertension progressing to decompensated HF that shares many of the hallmark biochemical and pathophysiologic...

Cardiac Effects of Exercise Training in Hypertension

“…us one of the major bene�ts of exercise training in hypertension is the preservation of cardiomyocyte cell number. Despite the potential for exercise training to increase myocardial mass in pressure overload, most studies have reported an improved phenotype aer training [25,30,46,61,[80][81][82][83][84][85][86][87]. One of the most proli�c bene�ts of exercise training is its improvement on adrenergic signaling.…”

“…Beyond improved AR responsiveness with training in hypertension, exercise has generally been shown to improve the overall heart phenotype and prolong survival [86,87]. 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.…”

The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart

“…Short axis M-mode echocardiograms on the LV were obtained for measurement of LV internal diameters at diastole (LVIDd) and systole (LVIDs), fractional shortening (FS), ejection fraction (EF), anterior wall thickness in diastole (AWTd), and posterior wall thickness in diastole (PWTd) as previously described ( 43 ).…”

Left ventricular remodeling with exercise in hypertension

“…While the control mechanisms for the induction of cardiomyocyte proliferation remain unclear, one theory purports the involvement of a resident population of cardiac progenitor cells (1, 30), which have been shown to increase their activity in stress-induced pathological conditions (1,28,31). In the hypertensive heart, cardiomyocyte proliferation may counteract apoptosis, thus reducing the progressive loss of cardiomyocytes.Recent studies from our laboratory, as well as others, have shown an overall phenotypical improvement for the myocardium with exercise training in hypertension (3,17,24,34,35,42). However, the precise putative mechanisms associated with the observed adaptations with exercise training remain unclear.…”