Ketone bodies maintain normal cardiac function and myocardial high energy phosphates during insulin-induced hypoglycemia in vivo.

It has been suggested that myocardial utilization of ketone bodies might cause deterioration of cardiac function. Therefore, the influence of ketonemia (mean: 1.3 and 3.3 mM) in the presence of hypoglycemia (mean: 33 mg/dl) on cardiac function, substrate utilization and myocardial high energy phosphate levels was studied in 10 mongrel dogs. Hypoglycemia alone led to a significant increase of mean aortic pressure, total peripheral resistance and myocardial oxygen consumption, but other hemodynamic parameters and regional myocardial function were not changed. Additional infusion of 3-hydroxybutyrate did not affect hemodynamic variables significantly. During both metabolic interventions in vivo phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy showed stable levels of myocardial Pi, PCr, ATP, as well as PCr/Pi (3.2-3.4) and PCr/ATP (3.0-3.2) ratios. Biochemical measurements revealed that ketonemia led to significant alterations in arterial concentrations and arterio-coronary venous differences of selected citric acid cycle intermediates, thus confirming previous reports which suggested a blockade of the 2-oxoglutarate-dehydrogenase reaction induced by ketone body oxidation. However, despite this blockade, the energy supply to the heart was not impaired as shown by normal NMR spectroscopy and cardiac performance. It is speculated that the blockade might be due to an enhanced NADH/NAD ratio.