title: A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats.
abstract: OBJECTIVE
  The myocardium is largely dependent upon oxidation of fatty acids for the production of ATP. Cardiac contractile abnormalities and failure have been reported after acute emotional stress and there is evidence that catecholamines are responsible for acute stress-induced heart injury. We hypothesized that carnitine deficiency increases the risk of stress-induced heart injury.
  
  
  METHODS
  Carnitine deficiency was induced in Wistar rats by adding 20 mmol/L of sodium pivalate to drinking water (P). Controls (C) received equimolar sodium bicarbonate and a third group (P + Cn) received pivalate along with 40 mmol/L carnitine. After 15 days, 6 rats/group were used to evaluate function of isolated hearts under infusion of 0.1 μM isoproterenol and 20 rats/group were submitted to a single subcutaneous administration of 50 mg/kg isoproterenol.
  
  
  RESULTS
  Isoproterenol infusion in C markedly increased the heart rate, left ventricular (LV) systolic pressure and coronary flow rate. In P rats, isoproterenol increased the heart rate and LV systolic pressure but these increases were not paralleled by a rise in the coronary flow rate and LV diastolic pressure progressively increased. Subcutaneous isoproterenol induced 15 % mortality rate in C and 50 % in P (p < 0.05). Hearts of surviving P rats examined 15 days later appeared clearly dilated, presented a marked impairment of LV function and a greater increase in tumor necrosis factor α (TNFα) levels. All these detrimental effects were negligible in P + Cn rats.
  
  
  CONCLUSIONS
  Our study suggests that carnitine deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress.
authors.affiliation: Research and Development, Sigma Tau Pharmaceuticals, Via Pontina Km 30.400, 00071, Pomezia, Italy.
authors.forename: Pietro Lo
authors.initials: PL
authors.lastname: Giudice
authors.affiliation: Institute of Nephrology, Department of Medicine, G. d'Annunzio University, Via dei Vestini, 66013, Chieti, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bonomini
authors.affiliation: Department of Research & Development, CoreQuest Sagl, Tecnopolo, Stabile Suglio, Via Cantonale 18, 6928, Manno, Switzerland. a.arduini@corequest.ch.
authors.forename: Arduino
authors.initials: A
authors.lastname: Arduini
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism*; D003971:Diastole / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D022124:Hyperammonemia / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009135:Muscular Diseases / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D007545:Isoproterenol; D002331:Carnitine
keywords: Carnitine; Heart injury; Isoprotenerol; Pivalic acid; Primary carnitine deficiency; Sympathetic activation