Physical training alters the pathogenesis of pacing-induced heart failure through endothelium-mediated mechanisms in awake dogs.
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.


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.
Wang
J
J
Department of Medicine and Institute of Comparative Medicine, College of Physicians and Surgeons of Columbia University, New York City, NY 10032, USA.
Yi
G H
GH
Knecht
M
M
Cai
B L
BL
Poposkis
S
S
Packer
M
M
Burkhoff
D
D
D000818:Animals; D001835:Body Weight; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D010805:Physical Conditioning, Animal; D014664:Vasodilation
D019001:Nitric Oxide Synthase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases