Fibrinogen/fibrin deposition and microvascular leakage caused by pulmonary ischemia‐reperfusion in the intact rabbit lung

Pulmonary ischemia‐reperfusion causes microvascular dysfunction and edema, resulting in ventilation‐perfusion mismatch. To study fibrinogen/fibrin (Fg/Fb) deposition in pulmonary microvessels, and its association with microvascular leakage during reperfusion, we examined subpleural microvessels by video microscopy. In anesthetized rabbits with open chest, we ventilated the lungs and caused ischemia by placing a removable clip on the right pulmonary artery for 2 h. Prior to reperfusion, we injected albumin labeled with fluorescein isothiocyanate and a fluorescently labeled polyclonal antibody to Fg/Fb, via the right atrium. During a 3 h reperfusion period, the right lung was observed during brief periods when the lungs were statically inflated (10 cm H 2 O). Fg/Fb deposition along pulmonary microvessels increased progressively as blood flow returned. Albumin leakage was greatest at sites of Fg/Fb deposition. Deposition and leakage were associated with increased expression of NADPH oxidase, superoxide dismutase, inducible nitric oxide synthase, and reactive nitrogen species formation in lung tissue. We present a model to study activation of endogenous Fg/Fb activity during acute lung injury. Our data indicate that Fg/Fb deposition along the pulmonary endothelium occurs during early reperfusion in the ventilated lung and could be a cause of increased microvascular permeability. (Supported by ALA of KY)