Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Abstract

. Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 289: H2030 -H2038, 2005. First published July 1, 2005; doi:10.1152/ajpheart.00526.2005.-Data regarding the effectiveness of chronic exercise training in improving survival in patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine the effect of exercise training on survival in a well-defined animal model of heart failure (HF), using the lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present with decompensated, dilated HF between ϳ18 and 23 mo of age. SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of age. Exercise training consisted of 6 mo of low-intensity treadmill running. Exercise training delayed the onset of overt HF and improved survival (P Ͻ 0.01), independent of any effects on the hypertensive status of the rats. Training delayed the myosin heavy chain (MyHC) isoform shift from ␣-to ␤-MyHC that was seen in sedentary animals that developed HF. Exercise was associated with a concurrent increase in cardiomyocyte length (Ϸ6%), width, and area and prevented the increase in the length-to-width ratio seen in sedentary animals in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum leptin levels observed in rats with HF were suppressed by low-intensity exercise training. No significant alterations in sarco (endo)plasmic reticulum Ca 2ϩ ATPase, phospholamban, or Na ϩ / Ca 2ϩ exchanger protein expression were found in response to training. Our results indicate that 6 mo of low-intensity exercise training delays the onset of decompensated HF and improves survival in the male SHHF rat. Similarly, exercise intervention prevented or suppressed alterations in several key variables that normally occur with the development of overt CHF. These data support the idea that exercise may be a useful and inexpensive intervention in the treatment of HF. myosin heavy chain; proteinuria; cardiomyocyte morphology; atrial natriuretic peptide; leptin HEART DISEASE is a leading cause of death among men and women in Western industrialized societies. Cardiovascular disease (CVD) currently affects over 70 million Americans, 65 million of which are estimated to have high blood pressure and nearly 5 million are diagnosed with congestive heart failure (CHF) (2). With the diagnosis of CHF, life expectancy decreases dramatically and chances of survival decrease with 70 -80% of patients dying within 8 yr (2). Although chronic exercise training has clearly been shown to be beneficial in attenuating risk factors for CVD, including high blood pressure and cholesterol levels, insulin resistance, and obesity (9,14,53,58), the utility of exercise as a clinical intervention for patients with developing CHF is less clear. Currently, there is a lack of clarity regarding the efficacy of chronic exercise training as a treatment and in reducing mortali...

Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure

“…The present study indicates that although CDS and PGPS enzyme activities were increased, the ability to sustain substrates for CL de novo biosynthesis during development of HF in SHHF rats was still compromised, at least in interfi brillar mitochondria. This was confi rmed by the decreased amount of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]linoleate incorporated into PA+PG formed in mitochondria at 15 and 22 months in SHHF rats compared with 2-months-old animals. The decreased availability of CTP, which is known to regulate the CL biosynthesis in isolated heart ( 40 ), may account for such a decrease in PA+PG in compensated and terminal mRNA from SHHF rats; (C) Tafazzin (TAZ) mRNA from SHHF rats; (D) TAZ mRNA in human nonfailing (NF) or idiopathic dilated cardiomyopathy (IDC); and (E) TAZ mRNA from Sprague Dawley rats.…”

“…The lean (Mcc fa cp Ϫ / Ϫ ) male SHHF rats used in this study typically exhibit severe hypertension by 5 months of age, which progresses to marked left ventricular hypetrophy by 15 months, and overt HF by 21-24 months of age ( 8,(12)(13)(14). To complement studies in the SHHF rat, left ventricular (LV) tissue explanted from human HF patients and nonfailing Sprague Dawley (SD) rats were also examined.…”

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure

“…COx blot densities were normalized to calsequestrin to control for potential loading differences (37). Calsequestrin was used as the loading control because it has been shown, unlike some other housekeeping proteins, to remain unaltered during the pathogenesis of HF (38).…”

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

“…Cardiomyocytes were isolated from whole hearts with modifications to methods previously described ( 44,45 ). Animals reacid (18:2) ( 2, 6, 16 ).…”