title: Cardiac function, substrate utilization, and myocardial energy metabolism studied with 31-P NMR spectroscopy during acute hypoglycemia and hyperketonemia.
abstract: Whether severe hypoglycemia alone or in combination with hyperketonemia might cause deterioration of cardiac function has been controversial. Therefore, the influence of acute hypoglycemia (mean 33 mg/dL) with and without hyperketonemia (mean 1.3 and 3.3 mM) on cardiac function, substrate utilization, and myocardial high energy phosphate levels was studied in 10 mongrel dogs. After 45 min of hypoglycemia, mean aortic pressure, total peripheral resistance, and myocardial oxygen consumption had increased significantly, but other hemodynamic parameters and regional myocardial function had not changed. Additional infusion of 3-hydroxybutyrate did not affect hemodynamic variables significantly. During both metabolic interventions in vivo phosphorus-31 nuclear magnetic resonance spectroscopy showed stable levels of myocardial phosphocreatinine, ATP, as well as the phosphocreatinine/ATP (3.0-3.2) ratio. Biochemical measurements revealed that hyperketonemia led to significant alterations in arterial concentrations and arteriocoronary 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 nuclear magnetic resonance spectroscopy and cardiac performance. It is speculated, that the blockade might be due to an enhanced NADH/NAD ratio.
authors.affiliation: Department of Pediatrics, University of California at San Diego, School of Medicine, La Jolla 92093.
authors.forename: J
authors.initials: J
authors.lastname: Breuer
authors.forename: K J
authors.initials: KJ
authors.lastname: Chung
authors.forename: E
authors.initials: E
authors.lastname: Pesonen
authors.forename: R H
authors.initials: RH
authors.lastname: Haas
authors.forename: B D
authors.initials: BD
authors.lastname: Guth
authors.forename: D J
authors.initials: DJ
authors.lastname: Sahn
authors.forename: J R
authors.initials: JR
authors.lastname: Hesselink
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D004285:Dogs; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D007657:Ketone Bodies / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D007657:Ketone Bodies; D010725:Phosphocreatine; D000255:Adenosine Triphosphate