Reduced substrate oxidation in postischemic myocardium: 13C and 31P NMR analyses.
13C and 31P nuclear magnetic resonance (NMR) spectra were used to assess substrate oxidation and high-energy phosphates in postischemic (PI) isolated rabbit hearts. Phosphocreatine (PCr) increased in nonischemic controls on switching from glucose perfusion to either 2.5 mM [3-13C]pyruvate (120%, n = 7) or [2-13C]acetate (114%, n = 8, P less than 0.05). ATP content, oxygen consumption (MVO2), and hemodynamics (dP/dt) were not affected by substrate availability in control or PI hearts. dP/dt was 40-60% lower in PI hearts during reperfusion after 10 min ischemia. Hearts reperfused with either pyruvate (n = 11) or acetate (n = 8) regained preischemic PCr levels within 45 s. Steady-state ATP levels were 55-70% of preischemia with pyruvate and 52-60% with acetate. Percent maximum [4-13C]glutamate signal showed reduced conversion of pyruvate to glutamate via the tricarboxylic acid (TCA) cycle at 4-min reperfusion (PI = 24 +/- 4%, means +/- SE; Control = 48 +/- 4%). The increase in 13C signal from the C-4 position of glutamate was similar to control hearts within 10.5 min. The increase in [4-13C]glutamate signal from acetate was not different between PI and control hearts. The ratio of [2-13C]Glu:[4-13C]Glu, reflecting TCA cycle activity, was reduced in PI hearts with acetate for at least 10 min (Control = 0.76 +/- 0.03; PI = 0.51 +/- 0.09) until steady state was reached. Despite rapid recovery of oxidative phosphorylation, contractility remained impaired and substrate oxidation was significantly slowed in postischemic hearts.
Lewandowski
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Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Johnston
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D000085:Acetates / Q000494:pharmacology; D000818:Animals; D002247:Carbon Isotopes; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010758:Phosphorus; D011773:Pyruvates / Q000494:pharmacology; D011817:Rabbits
D000085:Acetates; D002247:Carbon Isotopes; D011773:Pyruvates; D010758:Phosphorus