Nuclear magnetic resonance evaluation of metabolic and respiratory support of work load in intact rabbit hearts.
Pre-steady-state 13C nuclear magnetic resonance (NMR) spectra can provide a nondestructive probe of metabolic events associated with the physiology of intact organs. Therefore, the relation between phosphorylation state and intermediary metabolism in rabbit hearts, oxidizing [2-13C]acetate, was examined with a combination of 31P and 13C NMR. Multiple enrichment of the tissue glutamate pool with 13C as an index of metabolic turnover within the tricarboxylic acid cycle was readily observed as a function of work load. Dynamic changes in pre-steady-state 13C spectra evolved according to work load and correlated closely to respiratory rate in rabbit hearts perfused 1) under normal conditions (n = 7), 2) at basal metabolic rates (20 mM KCl arrest, n = 5), 3) and at heightened contractile state (10(-7) M isoproterenol, n = 7). The ratio of signal intensity arising from the secondary labeling sites within glutamate (C-2 and C-3) to that of the initial labeling site (C-4) reached steady state within 8.5 minutes in isoproterenol-treated hearts versus 18.5 minutes in control hearts. Work load did not affect glutamate concentration or fractional enrichment at the C-4 position, although an unlabeled fraction of glutamate persisted. Arrested hearts displayed slowed evolution of steady-state 13C enrichment with increased contributions from anaplerotic sources for tricarboxylic acid intermediate formation (32%) as compared with control (9%). Thus, the response of mitochondrial dehydrogenase activity to the demands of cardiac performance is likely to influence the recruitment of anabolic sources supplying the tricarboxylic acid cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
Lewandowski
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Section of Cardiology, Baylor College of Medicine, Houston, Tex.
D000085:Acetates / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002952:Citric Acid Cycle / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008955:Models, Cardiovascular; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits
D000085:Acetates; D002250:Carbon Radioisotopes; D005971:Glutamates; D010761:Phosphorus Radioisotopes; D010725:Phosphocreatine; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D007545:Isoproterenol