Myocardial cytoprotective efficacy of azapropazone in a canine heart model of regional ischemia and reperfusion.
The present study assessed the efficacy of azapropazone (AZA) in pentobarbital-anesthetized dogs subjected to 120 min of regional ischemia [left anterior descending coronary artery (LAD) ligation] followed by 5 h of reperfusion. Azapropazone was given 30 min prior to LAD occlusion (100 mg/kg i.v.), 35 min prior to LAD release (50 mg/kg, i.v.), and at 2.5 h postreperfusion (50 mg/kg i.v.). Regional myocardial blood flow (RMBF) and area at risk (AAR) were determined with radiolabeled microspheres. The degree and extent of ischemia (anaerobic metabolism) and necrosis were delineated with 14C-deoxy-2-D-glucose (14C-DG) and 111In-antimyosin, respectively, in control (n = 7) and AZA (n = 7)-treated groups. In mild (60-80% normal RMBF) and moderate (30-60% normal RMBF) flow-restricted areas, AZA resulted in a significant decrease in the degree and extent of ischemia (p less than 0.01) with the limitation of infarct size (p less than 0.01). However, AZA did not produce a significant infarct size limitation in the severe flow-restricted area (0-30% of normal RMBF). The effect of AZA is expressed primarily in moderate flow-restricted myocardium with the subsequent infarct size limitation.
Mousa
S A
SA
E.I. Du Pont de Nemours Co., Inc., Medical Product Department, Wilmington, Delaware.
Cooney
J M
JM
Thoolen
M J
MJ
Timmermans
P B
PB
D000693:Anaerobiosis; D000818:Animals; D001032:Apazone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D014227:Triazines / Q000627:therapeutic use*
D014227:Triazines; D001032:Apazone