Complement-mediated pulmonary edema in sheep

Incubation of plasma with zymosan results in complement activation. Infusion of zymosan-activated plasma (ZAP) into the pulmonary circulation in sheep results in a transient rise in pulmonary vascular resistance, accompanied by hypoxemia. This is associated with production of the vasoactive prostaglandin metabolite, thromboxane. We hypothesized that ZAP infusion caused pulmonary edema and may transiently alter pulmonary permeability to protein. Two sets of experiments were conducted involving six sheep. Three sheep underwent open lung biopsies during ZAP infusion, and electron microscopy documented early reversible interstitial pulmonary edema in response to ZAP infusion. Three other sheep were prepared with lung lymph fistulae and subjected to a similar infusion of ZAP. These studies documented a rapid rise in lymph flow and lymph protein clearance, occurring immediately upon infusion of ZAP. These experiments demonstrate a rapid reversible interstitial edema in sheep lung in response to ZAP infusion and suggest that permeability to protein may be transiently altered as a result of this injury.