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)C]glucose and [(3)H]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 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.
Korvald
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Department of Thoracic and Cardiovascular Surgery, University Hospital in Tromsø, N-9038 Tromsø, Norway. korvald@fagmed.uit.no
Elvenes
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OP
Myrmel
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002306:Cardiac Volume / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D013552:Swine
D000925:Anticoagulants; D002250:Carbon Radioisotopes; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000255:Adenosine Triphosphate; D006493:Heparin; D005947:Glucose; D011188:Potassium