Influence of myocardial substrate utilization on the oxygen consumption of the heart.
The effect of changing myocardial metabolism from predominantly lipid to predominantly carbohydrate utilization on myocardial oxygen consumption (MVO2) was studied in 10 closed-chest dogs. Oxygen saving potency of different metabolic interventions was quantified over a wide hemodynamic range by comparing the directly determined MVO2 with the hemodynamic parameter total left ventricular energy demand (Et), which correlates closely under control conditions with MVO2 (r = 0.98). Stimulation of carbohydrate metabolism by addition of glucose and beta-pyridyl carbinol or by activation of pyruvate dehydrogenase with dichloroacetate (DCA) shifted the cardiac respiratory quotient during beta-stimulation from 0.73 to 1.00 and 0.89, respectively, the nonesterified fatty acid/albumin ratio decreased from 4.0 to 0.5, or remained unchanged with DCA, and MVO2 was reduced by 25 and 16%, respectively. Therapeutic approaches aimed at decreasing MVO2 by changing substrate utilization are discussed.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006439:Hemodynamics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism*; D009540:Nicotinyl Alcohol / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013379:Substrate Specificity
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D009540:Nicotinyl Alcohol