Complement activation during hemorrhagic shock and resuscitation in swine.
Activation of the complement (C) cascade is known to play a key role in the adverse immune consequences of hemorrhagic trauma with subsequent shock and resuscitation. However, it is not clear whether hypovolemia per se, without trauma and resuscitation, can also lead to C activation. To address this question, we studied the presence, kinetics, and cause of C activation in a porcine model of hemorrhagic shock and resuscitation in the absence of trauma. Pigs were bled to and kept at 35 mmHg for 90 min, followed by hypotensive resuscitation with different fluids and, finally, with shed blood. The animals developed severe lactic acidosis between 30 and 90 min, which was accompanied by a trend for initial rise and subsequent 40% drop of CH50/mL, indicating massive C activation even before resuscitation, i.e., before reperfusion damage could have occurred. Resuscitation with plasma expanders caused 20% additional C consumption, whereas whole blood raised CH50/mL. Plasma C5a decreased initially and then significantly increased at 60 and 180 min, whereas thromboxane B2 showed a 3-fold increase at 30 and 60 min. Plasma LPS was also increased above baseline at 90 and 180 min. In in vitro studies with pig blood, spontaneous C5a formation, as well as zymosan-induced C consumption, was significantly enhanced under the conditions of lactic acidosis. Our data suggest that lactic acidosis, endotoxemia, and possibly other ischemia-related tissue alterations act in a vicious cycle in inducing C activation and, hence, aggravation of shock. The biphasic course of CH50/mL and C5a changes may reflect yet unrecognized physiological responses to hemorrhage-related C activation.
D000140:Acidosis, Lactic / Q000097:blood / Q000276:immunology; D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000097:blood; D008954:Models, Biological; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D034421:Sus scrofa; D013929:Thromboxane B2 / Q000097:blood; D015054:Zymosan / Q000494:pharmacology
D008070:Lipopolysaccharides; D019344:Lactic Acid; D013929:Thromboxane B2; D015936:Complement C5a; D003165:Complement System Proteins; D015054:Zymosan