In vivo phosphorus-31 NMR spectroscopy of abnormal myocardial high-energy phosphate metabolism during cardiac stress in hypertensive-hypertrophied non-human primates.
To study the functional and metabolic correlates of left ventricular hypertrophy [LVH] in non-human primates, 7 hypertensive baboons [papio anubis] with 4.6 +/- 0.1 years of hypertension produced by a two-kidney one-clip model, and echocardiographically documented concentric LVH underwent serial phosphorus-31 [P-31] NMR Spectroscopy studies at rest and during inotropic cardiac stress produced by dobutamine infusion [5 micrograms/kg/minute]. Responses in LVH baboons were compared to those in 5 normotensive, sex and weight-matched control animals. The ratio of P-31 NMR-S derived inorganic phosphates [Pi] to phosphocreatine [PCr] was significantly greater at rest in LVH baboons [0.53 +/- 0.06 versus controls = 0.41 +/- 0.17; P less than 0.05]. With dobutamine drug stress, the Pi/PCr ratio rose significantly in LVH baboons [0.77 +/- 0.15 versus 0.56 +/- 0.16; P less than 0.05 at 15 minutes]. Despite hemodynamic recovery, the 5 minute post-dobutamine Pi/PCr ratio remained elevated compared to baseline in LVH baboons only [0.78 +/- 0.16 versus 0.53 +/- 0.06; P less than 0.05]. In pre-instrumented baboons [n = 5], the 'transfer function' of cardiac work [heart rate x LV end-systolic pressure x + dp/dt max] versus Pi/PCr ratio was abnormally shifted rightward and downward [r = 0.80] with LVH as compared to the linearly increasing response in controls. We conclude that in vivo P-31 NMR Spectroscopy studies during dobutamine stress demonstrate reduced PCr stores, delayed metabolic recovery following cessation of inotropic stress, and an abnormal rightward shift in the 'transfer function' in LVH baboons.
Miller
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University of Cincinnati School of Medicine, Department of Medicine.
Walsh
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004280:Dobutamine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000150:complications*; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010215:Papio; D010710:Phosphates / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D013268:Stimulation, Chemical
D010710:Phosphates; D010725:Phosphocreatine; D004280:Dobutamine; D000255:Adenosine Triphosphate