Complement depletion with Naje haje cobra venom factor limits prostaglandin release and improves visceral perfusion in porcine endotoxic shock.
We tested the hypothesis that complement (C')-dependent release of prostaglandin (PG) I2 is an important factor contributing to the development of hypotension and low systemic vascular resistance index (SVRI) in endotoxic shock. Two groups (n = 7) of pentobarbital-anesthetized pigs (12-15 kg) were infused over 40 min with Escherichia coli lipopolysaccharide (LPS; 200 micrograms/kg) and continuously resuscitated with normal saline (1 ml/kg min): LPS-Control (no pretreatment) and LPS-Decomplemented (pretreatment 18 hr before study with 500-1,500 units of Naje haje cobra venom factor, CVF). Prior treatment with CVF: i) decreased the mean titer of total hemolytic C' to 15.9% of pretreatment levels; ii) significantly decreased post-LPS plasma concentrations of immunoreactive TxB2 (TxA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite); iii) abrogated the early transient decrease in cardiac index observed in the LPS-Control group; iv) tended to improve post-LPS visceral perfusion assessed using radioactive microspheres; and v) had no discernible effect on the late sustained decrease in SVRI observed following infusion of LPS. We conclude that C' activation is a major determinant of LPS-induced prostanoid release in vivo, although our results do not support the view that C'-dependent release of PGI2 is an important factor contributing to low SVRI in resuscitated endotoxic shock.
Fink
M P
MP
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Rothschild
H R
HR
Deniz
Y F
YF
Cohn
S M
SM
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D003165:Complement System Proteins / Q000032:analysis / Q000172:deficiency*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014781:Viscera / Q000098:blood supply / Q000187:drug effects*
D004546:Elapid Venoms; D008070:Lipopolysaccharides; C016310:cobra venom factor; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003165:Complement System Proteins; D011464:Epoprostenol