Systemic and lung physiological changes in rats after intravascular activation of complement

Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory e ffectors, products of complement activation contribute directly to generali zed manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemi c activation of complement with cobra venom factor (CVF), including blood p ressure, metabolic acidosis, changes in vascular permeability, and lung fun ction. High doses of CVF produced circulatory collapse (mean arterial press ure = 110 +/- 16 and 35 +/- 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO3- concentration = 27.8 +/- 1.7 and 9.6 +/ - 3.4 meq/l in control and with CVF, respectively, P, 0.05), extravasation of albumin into the lung and gut, and modest arterial hypoxemia (PO2 = 486 +/- 51 and 201 +/- 36 Torr in control and during 100% O-2 breathing, respec tively, P < 0.05). Prior depletion of complement protected against these ab normalities. Other interventions, including neutrophil depletion and cycloo xygenase inhibition, prevented lung injury but had much less effect on syst emic hemodynamics or gut permeability, suggesting that complement activatio n products induce injury by neutrophil- and cyclooxygenase-dependent pathwa ys in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.