CHANGES IN CEREBRAL BLOOD-FLOW AND CARBOHYDRATE-METABOLISM DURING ACUTE HYPERKETONEMIA

During starvation, brain energy metabolism in humans changes toward ox idation of ketone bodies. To investigate if this shift is directly cou pled to circulating blood concentrations of ketone bodies, we measured global cerebral blood flow (CBF) and global cerebral carbohydrate met abolism with the Kety-Schmidt technique before and during intravenous infusion with ketone bodies. During acute hyperketonemia (mean beta-hy droxybutyrate blood concentration 2.16 mM), cerebral uptake of ketones increased from 1.11 to 5.60 mu mol . 100 g(-1). min(-1), counterbalan ced by an equivalent reduction of the cerebral glucose metabolism from 25.8 to 17.2 . mol . 100 g(-1). min(-1), with the net result being an unchanged cerebral uptake of carbohydrates. In accordance with this, global cerebral oxygen metabolism was not significantly altered (144 v s. 135 mu mol . 100 g(-1). min(-1)). The unchanged global cerebral met abolic activity was accompanied by a 39% increase in CBF from 51.0 to 70.9 ml . 100 g(-1). min(-1) Regional analysis of the glucose metaboli sm by positron emission tomography-[F-18] fluoro-2-deoxy-D-glucose ind icated that mesencephalon does not oxidize ketone bodies to the same e xtent as the rest of the brain. It was concluded that the immediate ox idation of ketone bodies induced a decrease in cerebral glucose uptake in spite of an adequate glucose supply to the brain. Furthermore, acu te hyperketonemia caused a resetting of the coupling between CBF and m etabolism that could not be explained by alterations in arterial CO2 t ension or pH.