Non-invasive assessment of the effect of cardiac sympathetic innervation on metabolism of the human heart

The role of cardiac sympathetic nerves in the regulation of myocardial meta bolism is not well defined. Owing to the presence of incomplete reinnervati on, heart transplant recipients provide a unique model to study the effects of efferent sympathetic innervation. Using this model, we sought to determ ine the influence of cardiac sympathetic signals on substrate utilisation a nd overall oxidative metabolism. In 21 transplant recipients, positron emis sion tomography was applied to determine sympathetic innervation with the n oradrenaline analogue carbon-11 hydroxyephedrine, oxidative metabolism with carbon-11 acetate (n=14), and glucose utilisation with fluorine-18 fluorod eoxyglucose (n=7). The reinnervated area com prised 22%+/-20% of the left v entricle. Oxidative metabolism was similar in denervated and reinnervated m yocardium [0.06+/-0.01 vs 0.06+/-0.01/min for k(mono)], while glucose uptak e was significantly higher in denervated myocardium (6.9+/-6.6 vs 6.0+/-6.2 mu mol/min/100 g; P=0.03). Reinnervation mainly occurred in the territory of the left anterior descending artery, where retention of C-11-hydroxyephe drine (6.8+/-2.7%/min) was higher compared with territories of the left cir cumflex (4.1+/-1.7%/min: P<0.01) and right coronary (3.8+/-1.1%/min; P<0.01 ) arteries. Oxidative metabolism was similar in all three territories, but compared with the reinnervated territory of the left anterior descending ar tery (53%+/-16% of maximum), relative FDG uptake was higher in territories of the left circumflex (76%+/-6%, P<0.01) and right coronary (67%+/-10%, P< 0.05) arteries. Similar degrees of regional heterogeneity were not observed in normals. Thus, while overall energy production through oxidative metabo lism remains unaffected, cardiac utilisation of glucose in the fasting stat e is increased in the absence of catecholamine uptake sites. Innervated myo cardium, however, may preferentially utilise free fatty acids, suggesting a role for sympathetic tone in substrate utilisation.