title: Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice.
abstract: 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.affiliation: Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway. ole-jakob.how@fagmed.uit.no
authors.forename: O-J
authors.initials: OJ
authors.lastname: How
authors.forename: T S
authors.initials: TS
authors.lastname: Larsen
authors.forename: A D
authors.initials: AD
authors.lastname: Hafstad
authors.forename: A
authors.initials: A
authors.lastname: Khalid
authors.forename: E S P
authors.initials: ES
authors.lastname: Myhre
authors.forename: A J
authors.initials: AJ
authors.lastname: Murray
authors.forename: N T
authors.initials: NT
authors.lastname: Boardman
authors.forename: M
authors.initials: M
authors.lastname: Cole
authors.forename: K
authors.initials: K
authors.lastname: Clarke
authors.forename: D L
authors.initials: DL
authors.lastname: Severson
authors.forename: E
authors.initials: E
authors.lastname: Aasum
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007473:Ion Channels / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000071247:Uncoupling Protein 3; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000071247:Uncoupling Protein 3; D000077154:Rosiglitazone