TY - JOUR
T1 - Physical training alters the pathogenesis of pacing-induced heart failure through endothelium-mediated mechanisms in awake dogs
AU - Wang, Jie
AU - Yi, Geng Hua
AU - Knecht, Mathias
AU - Cai, Bo Lin
AU - Poposkis, Sulli
AU - Packer, Milton
AU - Burkhoff, Daniel
PY - 1997/10/21
Y1 - 1997/10/21
N2 - Background: Beneficial effects of exercise training on cardiovascular function in chronic heart failure (CHF) have been suggested previously but the underlying mechanisms are unknown. We tested whether daily exercise training improves systemic hemodynamics and preserves endothelium-mediated vasodilator function during development of heart failure. Methods and Results: Fifteen dogs were surgically instrumented for hemodynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another group underwent pacing plus daily exercise training (4.4±0.3 km/h, 2 h/d). Pacing-alone dogs developed CHF characterized by typical hemodynamic abnormalities, blunted endothelium-mediated vasodilator function in coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to GAPDH expression; normal, 1.15±0.31 versus CHF, 0.29±0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-mediated vasodilator function, and gene expression of ECNOS (0.72±0.16 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventricular end-diastolic pressure (7.7±0.3 to 19±3.4 mm Hg, P<.05), suggesting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF state. Conclusions: Long-term exercise training altered the natural history of heart failure due to rapid cardiac pacing. One of the underlying mechanisms is through the preservation of endothelial vasodilator function.
AB - Background: Beneficial effects of exercise training on cardiovascular function in chronic heart failure (CHF) have been suggested previously but the underlying mechanisms are unknown. We tested whether daily exercise training improves systemic hemodynamics and preserves endothelium-mediated vasodilator function during development of heart failure. Methods and Results: Fifteen dogs were surgically instrumented for hemodynamic measurements. One group of dogs underwent 4 weeks of cardiac pacing (210 bpm for 3 weeks and 240 bpm during week 4), and another group underwent pacing plus daily exercise training (4.4±0.3 km/h, 2 h/d). Pacing-alone dogs developed CHF characterized by typical hemodynamic abnormalities, blunted endothelium-mediated vasodilator function in coronary and femoral circulations, and decreased gene expression of endothelial constitutive nitric oxide synthase (ECNOS, normalized to GAPDH expression; normal, 1.15±0.31 versus CHF, 0.29±0.08, P<.05). Exercise training preserved normal hemodynamics at rest, endothelium-mediated vasodilator function, and gene expression of ECNOS (0.72±0.16 versus normal, P=NS). Inhibition of NO synthesis (nitro-L-arginine) in exercise-trained dogs abolished the preserved endothelium-mediated vasodilation of epicardial coronary arteries and elevated left ventricular end-diastolic pressure (7.7±0.3 to 19±3.4 mm Hg, P<.05), suggesting that the preservation of resting hemodynamics was in large part due to preserved endothelial function concealing the underlying CHF state. Conclusions: Long-term exercise training altered the natural history of heart failure due to rapid cardiac pacing. One of the underlying mechanisms is through the preservation of endothelial vasodilator function.
KW - Circulation
KW - Endothelium-derived factors
KW - Exercise
KW - Heart failure
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U2 - 10.1161/01.CIR.96.8.2683
DO - 10.1161/01.CIR.96.8.2683
M3 - Article
C2 - 9355910
AN - SCOPUS:0030772102
SN - 0009-7322
VL - 96
SP - 2683
EP - 2692
JO - Circulation
JF - Circulation
IS - 8
ER -