Development of cardiac dysfunction induced by repetitive transient myocardial ischemia is inhibited by edaravone in conscious rats

Clin Exp Pharmacol Physiol. 2009 Sep;36(9):e20-5. doi: 10.1111/j.1440-1681.2009.05178.x. Epub 2009 Mar 26.

Abstract

1. In the present study, we investigated the effects of treatment with the hydroxyl radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) on myocardial dysfunction induced by transient but frequent ischaemia in conscious rats. 2. Conscious male Wistar rats were subjected to repetitive ischaemia (RI; 40 s ischaemia every 20 min for 72 h). After the ninth episode of RI, edaravone (1 mg/kg, i.v., at each ischaemic event) or vehicle control (acetate buffer solution, i.v.) was administered. Dilation of the left ventricle (LV) after the eighth RI (fractional area change; %FAC(initial)) and after the final RI (%FAC(final)) was determined by comparing measurements (12 MHz echocardiogram) at these time-points with baseline LV area prior to RI. 3. In controls, %FAC(final) was correlated with %FAC(initial) (r = 0.98; P < 0.0001), making %FAC(initial) a predictor of %FAC(final). Edaravone treatment shifted the %FAC(initial)–%FAC(final) relationship downward (P < 0.0001), indicating that edaravone inhibited progression of LV dilation. In addition, %FAC(final) was correlated with myocardial generation of reactive oxygen species (ROS) in control samples (r = 0.88, P = 0.008), although both %FAC(final) and ROS were suppressed by edaravone treatment (P = 0.016). 4. We conclude that repetitive transient ischaemia in conscious rats induced development of cardiac dysfunction and that this phenomenon was inhibited by edaravone. We speculate that edaravone is a potential therapeutic agent that may interfere with the progression of cardiac dysfunction in high-risk patients with RI.

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Consciousness
  • Disease Models, Animal
  • Edaravone
  • Free Radical Scavengers / pharmacology*
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / physiopathology
  • Hypertrophy, Left Ventricular / prevention & control*
  • Male
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Ultrasonography
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / prevention & control*
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects

Substances

  • Free Radical Scavengers
  • Reactive Oxygen Species
  • Edaravone
  • Antipyrine