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 [C-14]glucose and [H-3]oleate 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 . beat(-1) . 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.