Evaluation of the effect of azapropazone on neutrophil migration in regional myocardial ischaemia/reperfusion injury in rabbits.
1. The purpose of the present study was to determine the myocardial cytoprotective efficacy of azapropazone (AZA) and its potential site of action on neutrophil infiltration into reperfused/ischaemic myocardium with or without in vivo activation of neutrophils in rabbits. 2. AZA, 100 mg kg-1, was administered i.v. 10 min after occlusion of the left circumflex (LCX) artery in rabbits with and without pretreatment with phorbol myristate acetate ester (PMA). The LCX occlusion was then released at 10 min after AZA administration. Haemodynamic parameters (heart rate, LV pressure, mean arterial blood pressure and dp/dt) were monitored throughout the experiment. After 60 min reperfusion, the area at risk was delineated and the heart was then excised and divided into epi- and endocardial pieces for analysis of myeloperoxidase activity. 3. AZA inhibited neutrophil infiltration into the reperfused/ischaemic rabbit myocardium with and without PMA treatment. The inhibition of neutrophil infiltration was more apparent in the epicardium than in the endocardium. Additionally, AZA inhibited to a similar extent the in vivo PMA-stimulated neutrophil migration into the epicardium and endocardium area at risk. AZA had no significant effect on the haemodynamic parameters as compared to control. 4. AZA administered in an anaesthetized rabbit model of LCX occlusion/reperfusion resulted in the reduction of infarct size. 5. It is concluded that AZA has significant inhibitory effects on neutrophil migration which might contribute to its myocardial cytoprotective effect.
Mousa
S A
SA
E.I. du Pont de Nemours & Co., Medical Products Department, Wilmington, DE 19880-0400.
Brown
R
R
Thoolen
M J
MJ
Smith
R D
RD
D000818:Animals; D001032:Apazone / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002464:Cell Migration Inhibition; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*
D014227:Triazines; D009195:Peroxidase; D001032:Apazone; D013755:Tetradecanoylphorbol Acetate