Myocardial cytoprotective efficacy of azapropazone in a swine model of regional myocardial ischemia/reperfusion injury.
The purpose of the present study is to determine the myocardial cytoprotective efficacy of azapropazone (AZA) on regional myocardial function in anesthetized swine model of regional myocardial ischemia/reperfusion injury. AZA was administered (100 mg/kg, i.v.) 15 minutes prior to reflow. The left anterior descending (LAD) coronary artery occlusion was maintained for a total of 30 minutes and then reperfused for 120 minutes. The effects of AZA on regional segmental shortening (% SS) as well as on neutrophil migration were examined in the (proximal) central and border (distal) zones within the area at risk (AAR). AZA reduced the incidence of myocardial fibrillation which occurred in some animals during the LAD occlusion/reperfusion periods. AZA produced a significant recovery of left ventricular segmental shortening (% SS) in the border, but not in the central zones within the AAR. No significant differences in the hemodynamic parameters were observed between the AZA (n = 14) and the saline-treated (n = 17) groups. AZA produced a significant inhibition of neutrophil migration (as evident from the decrease in myeloperoxidase activity) into epi- and endocardium central and border zones within the AAR. It is concluded that AZA may elicit its cardioprotection in moderately but not in severely injured myocardium by inhibiting the neutrophil migration.
Mousa
S A
SA
Medical Products Department, Cardiovascular Science Section, E.I. du Pont de Nemours and Co.
Ritger
R
R
D000818:Animals; D001032:Apazone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002464:Cell Migration Inhibition; D003250:Constriction; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012307:Risk Factors; D013552:Swine; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology
D009195:Peroxidase; D001032:Apazone