Blockade of histamine receptors and thrombin-induced microembolic pulmonary edema in the rat

Pulmonary edema was induced by an intravenous infusion of bovine thrombin, 500 NIH/kg b.w., given in 5 min, in rats in which fibrinolysis had been inhibited by an intraperitoneal injection of the fibrinolysis inhibitor AMCA. Ninety minutes after termination of the thrombin infusion the lung weight was increased from 1.09 +/- 0.07 to 3.14 +/- 0.12 g due to edema. A high albumin concentration in the extravascular water indicated that the edema was a consequence of increased permeability in the microcirculation. In rats injected with the H1 histamine receptor antagonist mepyramine maleate and H2 receptor antagonist cimetidine after the thrombin infusion, the lung weight was significantly lower at 90 min (2.68 +/- 0.33 g), and the amount of edema as calculated morphometrically was slightly but significantly reduced. The concentration of albumin in the extravascular water (i.e. in the edema fluid) in rats subjected to histamine receptor blockade was unchanged, indicating that the slight decrease in edema was a result of decreased filtration pressure and not of an effect on microvascular permeability.