Function and bioenergetics in isolated perfused trained rat hearts.
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 we correlated this with assessment of high-energy phosphate (HEP) metabolites from simultaneous 31P nuclear magnetic resonance (NMR) measurements. Furthermore, in vivo enzymatic studies were carried out with 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 exhibited improved systolic and diastolic function compared with hearts from sedentary animals. After 16 min 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 to 71.0 +/- 3.3 mmHg in control hearts and to 55.3 +/- 4.8 mmHg in trained hearts (P < 0.05). Trained hearts also showed more rapid and complete recovery of function during reoxygenation and greater coronary flow per gram of heart throughout the entire protocol. Functional differences were not accompanied by differences in HEP 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 (CrK) rate constant in trained hearts of 18% while beating, whereas in vitro enzymatic analysis revealed a 16% increase in the ratio of mitochondrial CrK 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 HEP levels but may reflect adaptations in the CrK system.
Spencer
R G
RG
National Institutes of Health, National Institute on Aging, Baltimore, Maryland 21224, USA.
Buttrick
P M
PM
Ingwall
J S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D010100:Oxygen