Myocardial substrate metabolism influences left ventricular energetics in vivo

The myocardial oxygen consumption (MVO(2)) to left ventricular pressure-volume area (PVA) relationship is assumed unaltered by substrates, despite varying phosphate-to-oxygen ratios and possible excess MVO(2) associated with fatty acid consumption. The validity of this assumption was tested in vivo. Left ventricular volumes and pressures were assessed with a combined conductance-pressure catheter in eight anesthetized pigs. MVO(2) was calculated from coronary flow and arterial-coronary sinus O(2) differences. Metabolism was altered by glucose-insulin-potassium (GIK) or Intralipid-heparin (IH) infusions in random order and monitored with (14)Cglucose and (3)Holeate tracers. Profound shifts in glucose and fatty acid oxidation were observed. Contractility, coronary flow, and slope of the MVO(2)-PVA relationship were unchanged during GIK and IH infusions. MVO(2) at zero PVA (unloaded MVO(2)) was 0.16 +/- 0.13 J x beat(-1) x 100 g(-1) higher during IH compared with GIK infusion (P = 0.001), a 48% increase. The study demonstrates a marked energetic advantage of glucose oxidation in the myocardium, profoundly affecting the MVO(2)-PVA relationship. This may in part explain the "oxygen-wasting" effect of lipid-enhancing interventions such as adrenergic drugs and ischemia.