Journal of Applied Physiology AJP: Heart and Circulatory Physiology
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J Appl Physiol 90: 2289-2295, 2001;
8750-7587/01 $5.00
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Vol. 90, Issue 6, 2289-2295, June 2001

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

John G. Younger1, Nobuyoshi Sasaki4, Joao Delgado1, Angela C. Ko1, Trac X. Nghiem1, Michael D. Waite3, Gerd O. Till2, and Peter A. Ward2

Departments of 1 Emergency Medicine and 2 Pathology, The University of Michigan, Ann Arbor, Michigan 48109; 3 Department of Emergency Medicine, The Ohio State University, Columbus, Ohio 43210; and 4 Department of Anesthesiology, Jikei University, Tokyo 105, Japan

Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory effectors, products of complement activation contribute directly to generalized manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemic activation of complement with cobra venom factor (CVF), including blood pressure, metabolic acidosis, changes in vascular permeability, and lung function. High doses of CVF produced circulatory collapse (mean arterial pressure = 110 ± 16 and 35 ± 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> 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% O2 breathing, respectively, P < 0.05). Prior depletion of complement protected against these abnormalities. Other interventions, including neutrophil depletion and cyclooxygenase inhibition, prevented lung injury but had much less effect on systemic hemodynamics or gut permeability, suggesting that complement activation products induce injury by neutrophil- and cyclooxygenase-dependent pathways in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.

shock; C5a; neutrophils; cyclooxygenase-1 and -2; cobra venom factor


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