Effects of platelet-activating factor antagonist SRI 63-441 on endotoxemia in sheep.

Abstract

We investigated whether platelet-activating factor (PAF) mediates endotoxin-induced systemic and pulmonary vascular derangements by studying the effects of a selective PAF receptor antagonist, SRI 63-441, during endotoxemia in sheep. Endotoxin infusion (1.3 micrograms/kg over 0.5 h) caused a rapid, transient rise in pulmonary arterial pressure (Ppa) from 16 +/- 3 to 36 +/- 10 mmHg (P less than 0.001) and pulmonary vascular resistance (PVR) from 187 +/- 84 to 682 +/- 340 dyn.s.cm-5 (P less than 0.05) at 0.5 h, followed by a persistent elevation in Ppa to 22 +/- 3 mmHg and in PVR to 522 +/- 285 dyn.s.cm-5 at 5 h in anesthetized sheep. Arterial PO2 (PaO2) decreased from 341 +/- 79 to 198 +/- 97 (P less than 0.01) and 202 +/- 161 Torr at 0.5 and 5 h, respectively (inspired O2 fraction = 1.0). SRI 63-441, 20 mg.kg-1.h-1 infused for 5 h, blocked the early rise in Ppa and PVR and fall in PaO2, but had no effect on the late phase pulmonary hypertension or hypoxemia. Endotoxin caused a gradual decrease in mean aortic pressure, which was unaffected by SRI 63-441. Infusion of SRI 63-441 alone caused no hemodynamic alterations. In follow-up studies, endotoxin caused an increase in lung lymph flow (QL) from 3.8 +/- 1.1 to 14.1 +/- 8.0 (P less than 0.05) and 12.7 +/- 8.6 ml/h at 1 and 4 h, respectively. SRI 63-441 abolished the early and attenuated the late increase in QL.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: C N Sessler, F L Glauser, D Davis, A A Fowler 3rd
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 65 Issue 6 Pg. 2624-31 (Dec 1988) ISSN: 8750-7587 [Print] United States
• PMID: 3145934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endotoxins
• Platelet Activating Factor
• Quinolinium Compounds
• SRI 63-441
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Endotoxins (toxicity)
• Hemodynamics (drug effects)
• Leukopenia (etiology)
• Lymph (drug effects, physiology)
• Platelet Activating Factor (antagonists & inhibitors)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pulmonary Circulation (drug effects)
• Pulmonary Gas Exchange (drug effects)
• Quinolinium Compounds (pharmacology)
• Sheep
• Toxemia (blood, etiology, physiopathology)