Antiischemic effects of pirsidomine, a new nitric oxide donor

Eur J Pharmacol. 1994 May 23;257(3):267-73. doi: 10.1016/0014-2999(94)90138-4.

Abstract

The antiischemic effect of pirsidomine (CAS 936 (3-(cis-2,6-dimethylpiperidino)-N-(4-methoxybenzoyl))-sydnon imine), a new nitric oxide donor, was investigated in a model of myocardial infarction in the dog. Dogs were anaesthetised, thoracotomized, and the left descending coronary artery was occluded for 6 h. Pirsidomine was given intraduodenally (i.d.) at the dose of 1.0 mg/kg to 11 dogs 30 min prior to coronary occlusion. Eleven dogs received the solvent i.d. and served as controls. Pirsidomine administration completely prevented the increase in left ventricular end-diastolic pressure and pulmonary artery pressure induced by the coronary occlusion and resulted in a marked decrease in systolic and diastolic blood pressure, cardiac output, left ventricular contractility, left ventricular work and left ventricular oxygen consumption. Additionally, pirsidomine completely prevented the occlusion-induced increase in flow in the non-occluded circumflex coronary artery. Regional blood flow measurements (with radioactive microspheres) revealed that pirsidomine induced a significant reduction in blood flow in the non-ischemic areas (both epi- and endocardial) but in the course of the ischemia, significantly increased flow in the ischemic epicardial areas. Infarct-size (triphenyltetrazolium chloride technique) in control dogs was 45% of the area at risk, but only 26% (P < 0.05) in pirsidomine-treated dogs. Thus, pirsidomine had a marked antiischemic effect in this model. This was probably due to the hemodynamic unloading of the heart as well as to redistribution of blood from the non-ischemic to the ischemic areas of the myocardium.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Coronary Circulation / drug effects
  • Dogs
  • Female
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / drug therapy*
  • Myocardial Ischemia / drug therapy
  • Myocardium / metabolism
  • Oxygen Consumption / drug effects
  • Sydnones / pharmacology
  • Sydnones / therapeutic use*
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*
  • Ventricular Function, Left / drug effects

Substances

  • Sydnones
  • Vasodilator Agents
  • pirsidomine