In vivo phosphorus-31 NMR spectroscopy of abnormal myocardial high-energy phosphate metabolism during cardiac stress in hypertensive-hypertrophied non-human primates

Abstract

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 µg/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<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<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<0.05]. In pre-instrumented baboons [n=5], the ‘transfer function’ of cardiac work [heart rate × LV end-systolic pressure × + 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 thatin 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.