A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats

Cardiovasc Drugs Ther. 2016 Apr;30(2):119-27. doi: 10.1007/s10557-016-6647-4.

Abstract

Purpose: 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.

Keywords: Carnitine; Heart injury; Isoprotenerol; Pivalic acid; Primary carnitine deficiency; Sympathetic activation.

MeSH terms

  • Animals
  • Cardiomyopathies / metabolism*
  • Carnitine / deficiency*
  • Carnitine / metabolism*
  • Diastole / drug effects
  • Heart / drug effects
  • Heart Diseases / chemically induced*
  • Heart Diseases / metabolism*
  • Heart Rate / drug effects
  • Hyperammonemia / metabolism*
  • Isoproterenol / pharmacology*
  • Male
  • Muscular Diseases / metabolism*
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism*
  • Oxidation-Reduction / drug effects
  • Rats
  • Rats, Wistar
  • Ventricular Function, Left / drug effects

Substances

  • Isoproterenol
  • Carnitine

Supplementary concepts

  • Systemic carnitine deficiency