Antiischemic effects of pirsidomine, a new nitric oxide donor.

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.

• Authors: P A Martorana, B Kettenbach, H Bohn, K Schönafinger, R Henning
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 257 Issue 3 Pg. 267-73 (May 23 1994) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8088346 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Sydnones
• Vasodilator Agents
• pirsidomine

Topics

• 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, therapeutic use)
• Vasodilator Agents (pharmacology, therapeutic use)
• Ventricular Function, Left (drug effects)