Function and bioenergetics in the isolated perfused trained rat
heart.
Spencer, Richard G. S., Peter M. Buttrick, and Joanne S. Ingwall.
National Institutes of Health, National Institute on Aging,
Baltimore, MD 21224, Montefiore Medical Center, Albert Einstein
College of Medicine, Bronx, NY 10467, Harvard Medical School, Brigham
and Women's Hospital, Boston, MA 02115
APStracts 3:0288H, 1996.
To evaluate the resistance of physiologically hypertrophied hearts to
hypoxic insult, we quantified the development of functional deficits
during hypoxia and reoxygenation in hypertrophied hearts from swim
-trained female rats, and correlated this with assessment of high
-energy phosphate (HEP) metabolites from simultaneous 31P nuclear
magnetic resonance (NMR) measurements. Further, in vivo enzymatic
studies were carried out using saturation transfer NMR under well
-oxygenated perfusion conditions for both beating and KCl-arrested
hearts. Finally, in vitro enzymatic assays were performed. During
hypoxia, the trained hearts were found to exhibit improved systolic
and diastolic function as compared to hearts from sedentary animals.
After 16 minutes of hypoxia, left ventricular (LV) developed pressure
fell to 9% of baseline in control hearts but to only 21% of baseline
in trained hearts (p<0.01). LV diastolic function was also
improved by training, increasing during hypoxia from a baseline of 10
mm Hg to 71.0 3.3 mm Hg in control hearts and to 55.3 4.8 mm Hg in
trained hearts (p<0.05). Trained hearts also showed more rapid
and complete recovery of function during reoxygenation, as well as
greater coronary flow per gram of heart throughout the entire
protocol. Functional differences were not accompanied by differences
in HEP's at baseline; moreover, ATP and phosphocreatine (PCr) loss
during hypoxia was similar between control and trained hearts, as was
the recovery of PCr during reoxygenation. Saturation transfer
experiments showed an increase in the forward creatine kinase (CK)
rate constant in trained hearts of 18% while beating, while in vitro
enzymatic analysis revealed a 16% increase in the ratio of
mitochondrial CK (mito-CK) to citrate synthase activity in LV tissue.
Thus, the relative preservation of function in hearts from trained
rats could not be accounted for by overall high-energy phosphate
levels, but may reflect adaptations in the CK system.
Received 1 February 1996; accepted in final form 9 July 1996.
APS Manuscript Number H93-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996