title: Detrimental effects of complement activation in hemorrhagic shock.
abstract: The complement system has been implicated in early inflammatory events and a variety of shock states. In rats, we measured complement activation after hemorrhage and examined the hemodynamic and metabolic effects of complement depletion before injury and worsening of complement activation after hemorrhage and resuscitation [with a carboxypeptidase N inhibitor (CPNI), which blocks the clearance of C5a]. Rats were bled to a mean arterial pressure of 30 mmHg for 50 min and were then resuscitated for 2 h. Shock resulted in significant evidence of complement consumption, with serum hemolytic activity being reduced by 33% (P < 0.05). Complement depletion before injury did not affect hemorrhage volume (complement depleted = 28 +/- 1 ml/kg, complement intact = 29 +/- 1 ml/kg, P = 0.74) but improved postresuscitation mean arterial pressure by 37 mmHg (P < 0.05) and serum bicarbonate levels (complement depleted = 22 +/- 3 meq/ml, complement intact = 13 +/- 8 meq/ml, P < 0.05). Pretreatment with CPNI was lethal in 80% of treated animals vs. the untreated hemorrhaged group in which no deaths occurred (P < 0.05). In this model of hemorrhagic shock, complement activation appeared to contribute to progressive hypotension and metabolic acidosis seen after resuscitation. The lethality of CPNI during acute blood loss suggests that the anaphylatoxins are important in the pathophysiological events involved in hemorrhagic shock.
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan 48109-0303, USA. jyounger@umich.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Younger
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: M D
authors.initials: MD
authors.lastname: Waite
authors.forename: H N
authors.initials: HN
authors.lastname: Murray
authors.forename: E F
authors.initials: EF
authors.lastname: Saleh
authors.forename: Z B
authors.initials: ZB
authors.lastname: Ravage
authors.forename: R B
authors.initials: RB
authors.lastname: Hirschl
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
authors.forename: G O
authors.initials: GO
authors.lastname: Till
authors.forename: Z A
authors.initials: ZA
authors.lastname: Ravage
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure; D003167:Complement Activation / Q000187:drug effects; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015996:Survival Rate
chemical_list: D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; C016310:cobra venom factor; D001121:Lysine Carboxypeptidase