Efficacy of a monoclonal antibody (MoAb 60.3) in reducing myocardial injury resulting from ischemia/reperfusion in the ferret.
The myocardial salvage efficacy of a monoclonal antibody (MoAb 60.3) directed at the CDw 18 membrane antigen complex essential for normal neutrophil function was evaluated in a ferret occlusion/reperfusion model. When infused i.v. over a 10-min interval beginning at the 45th minute of a 90-min occlusion at a fixed dose of 2 mg/kg, the antibody afforded 33 and 45% reductions in infarct size following reperfusion intervals of 6 and 24 h, respectively. Administration of that same dose via the left atrium over 1 h beginning at the 75th minute of occlusion and continuing until the 45th minute of reflow resulted in only a 14% reduction in infarct size. If MoAb 60.3 administration was withheld until the 5th-15th minute of reperfusion, the mean levels of salvage were 19 and 8%, respectively, following 6- and 24-h periods of reflow. Time-course hemodynamic data indicated that the monoclonal antibody caused no alterations in oxygen utilization that might be responsible for the levels of salvage observed.
Gomoll
A W
AW
Department of Cardiovascular Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Lekich
R F
RF
Grove
R I
RI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D005289:Ferrets / Q000276:immunology*; D006321:Heart / Q000033:anatomy & histology; D006352:Heart Ventricles / Q000033:anatomy & histology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal