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.