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Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate

¹United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics; ²Department of Molecular and Human Genetics, Baylor College of Medicine; ³Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas; ⁴Cardiovascular Research Group, Department of Pediatrics and Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; and ⁵Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio

Submitted 13 December 2006 ; accepted in final form 27 June 2007

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H₂O afterload), hearts were challenged with increased workload (140 cm H₂O afterload plus 1 µM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

fatty acids; glucose; glycogen; triglyceride

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