Protective effects of a specific platelet activating factor (PAF) antagonist, WEB 2086, in traumatic shock.
We have investigated the role of platelet activating factor (PAF) in the pathogenesis of a murine model of traumatic shock using WEB 2086, a specific antagonist of PAF. WEB 2086 (0.5 mg/kg) significantly reversed the decrease in mean arterial blood pressure (MABP) induced by PAF (0.3 micrograms/kg) in anesthetized rats. Anesthetized rats were subjected to Noble-Collip drum trauma. Traumatized rats treated with WEB 2086 (0.5 mg/kg bolus followed by infusion at 0.5 mg/kg/hr) maintained a higher MABP than those receiving only the vehicle (0.9% NaCl). Improvement in MABP paralleled a significant increase in overall survival time (p less than 0.01) in rats receiving WEB 2086 (0.5 mg/kg). WEB 2086 also significantly attenuated the plasma accumulation of the lysosomal hydrolase, cathepsin D and of free amino-nitrogen compounds, compared to shocked rats receiving only the vehicle. Furthermore, the production of the cardiotoxic peptide, myocardial depressant factor (MDF) was also blunted by WEB 2086. These results suggest that PAF may be an important mediator in the pathogenesis of traumatic shock in rats. Furthermore, PAF receptor antagonists may be useful as therapeutic agents when given early in the course of ischemic and shock states.
Stahl
G L
GL
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Bitterman
H
H
Lefer
A M
AM
D000818:Animals; D001381:Azepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D008297:Male; D051379:Mice; D009201:Myocardial Depressant Factor / Q000097:blood; D009584:Nitrogen / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012774:Shock, Traumatic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014227:Triazines / Q000627:therapeutic use*; D014230:Triazoles
D001381:Azepines; D009201:Myocardial Depressant Factor; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; D002402:Cathepsin D; D009584:Nitrogen