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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1373    most recent 01264.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Boardman, N. Articles by Aasum, E. Search for Related Content PubMed PubMed Citation Articles by Boardman, N. Articles by Aasum, E.

Increased O₂ cost of basal metabolism and excitation-contraction coupling in hearts from type 2 diabetic mice

¹Faculty of Medicine, Department of Medical Physiology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway; and ²Faculty of Medicine, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada

Submitted 5 December 2008 ; accepted in final form 13 March 2009

We have reported previously that hearts from type 2 diabetic (db/db) mice show decreased cardiac efficiency due to increased work-independent myocardial O₂ consumption (unloaded MO₂), indicating higher O₂ use for nonmechanical processes such as basal metabolism (MO_2BM) and excitation-contraction coupling (MO_2ECC). Although alterations in cardiac metabolism and/or Ca²⁺ handling may contribute to increased energy expenditure in diabetic hearts, direct measurements of the O₂ cost for these individual processes have not been determined. In this study, we 1) validate a procedure for measuring unloaded MO₂ directly (MO_2unloaded) and for determining MO_2BM and MO_2ECC separately in isolated perfused mouse hearts and 2) determine O₂ cost for these processes in hearts from db/db mice. Unloaded MO₂, extrapolated from the relationship between cardiac work (measured as pressure-volume area, PVA) and MO₂, was found to correspond with MO₂ measured directly in unloaded retrograde perfused hearts (MO_2unloaded). MO₂ in K⁺-arrested hearts was defined as MO_2BM; the difference between MO_2unloaded and MO_2BM represented MO_2ECC. This procedure was validated by demonstrating that elevations in perfusate fatty acid (FA) and/or Ca²⁺ concentrations resulted in changes in either MO_2BM and/or MO_2ECC. The higher MO_2unloaded in db/db mice was due to both a higher MO_2BM and MO_2ECC. Elevation of glucose and insulin decreased FA oxidation and reduced both MO_2unloaded and MO_2BM. In conclusion, this study provides direct evidence that MO_2BM and MO_2ECC are elevated in diabetes and that acute metabolic interventions can have a therapeutic benefit in diabetic hearts due to a MO₂-lowering effect.

cardiac efficiency; pressure-volume area; myocardial oxygen consumption; substrate oxidation