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.