title: Dichloroacetate selectively improves cardiac function and metabolism in female and male rainbow trout.
abstract: Cardiac tissue from female rainbow trout demonstrates a sex-specific preference for exogenous glucose and glycolysis, impaired Ca(2+) handling, and a greater tolerance for hypoxia and reoxygenation than cardiac tissue from male rainbow trout. We tested the hypothesis that dichloroacetate (DCA), an activator of pyruvate dehydrogenase, enhances cardiac energy metabolism and Ca(2+) handling in female preparations and provide cardioprotection for hypoxic male tissue. Ventricle strips from sexually immature fish with very low (male) and nondetectable (female) plasma sex steroids were electrically paced in oxygenated or hypoxic Ringer solution with or without 1 mM DCA. In the presence of 5 mM glucose, aerobic tissue from male trout could be paced at a higher frequency (1.79 vs. 1.36 Hz) with lower resting tension and less contractile dysfunction than female tissue. At 0.5 Hz, DCA selectively reduced resting tension below baseline values and lactate efflux by 75% in aerobic female ventricle strips. DCA improved the functional recovery of developed twitch force, reduced lactate efflux by 50%, and doubled citrate in male preparations after hypoxia-reoxygenation. Independent of female sex steroids, reduced myocardial pyruvate dehydrogenase activity and impaired carbohydrate oxidation might explain the higher lactate efflux, compromised function of the sarcoplasmic reticulum, and reduced mechanical performance of aerobic female tissue. Elevated oxidative metabolism and reduced glycolysis might also underlie the beneficial effects of DCA on the mechanical recovery of male cardiac tissue after hypoxia-reoxygenation. These results support the use of rainbow trout as an experimental model of sex differences of cardiovascular energetics and function, with the potential for modifying metabolic phenotypes and cardioprotection independent of sex steroids.
authors.affiliation: Department of Biological Sciences, Idaho State University, Pocatello, Idaho.
authors.forename: Pavan K
authors.initials: PK
authors.lastname: Battiprolu
authors.affiliation: Department of Biological Sciences, Idaho State University, Pocatello, Idaho rodnkenn@isu.edu.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rodnick
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D019343:Citric Acid / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010641:Phenotype; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000378:metabolism; D012737:Sex Factors; D018754:Ventricular Dysfunction / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D020536:Enzyme Activators; D019343:Citric Acid; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D030481:Pyruvate Dehydrogenase (Lipoamide); D005947:Glucose; D002118:Calcium
keywords: cardiac; dichloroacetate; glucose; hypoxia; lactate; rainbow trout; sex differences