Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice.

Journal article

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice.

Authors: How, O; Larsen, T; Hafstad, A; Khalid, A; Myhre, E

• Journal: Archives of physiology and biochemistry
• Volume: 113
• Issue: 4-5
• Pages: 211-220
• Publication date: 2007-01-01
• DOI: 10.1080/13813450701783281
• EISSN: 1744-4160
• ISSN: 1381-3455
• Language: English
• Keywords: Oxygen Consumption; Reperfusion Injury; Heart; Diabetes Mellitus, Type 2; Mitochondrial Proteins; Ischemia; Ion Channels; Cardiovascular Physiological Phenomena; Male; Organ Size; Coronary Vessels; Blood Glucose; Animals; Oxidation-Reduction; RNA, Messenger; Mice, Inbred C57BL; Body Weight; Thiazolidinediones; Lipid Metabolism; Female; Ventricular Function; Mice