Effect of methysergide pretreatment on thrombin-induced pulmonary oedema in the rat.

Microembolic pulmonary oedema was induced by injection of thrombin (500 NIH units/kg body weight) i.v. in rats in which fibrinolysis had been inhibited by pretreatment with trans-4-aminomethyl-cyclohexanoid-carboxylic acid (AMCA). To evaluate the role of serotonin in this condition the effect of pretreatment with the antiserotonin compound methysergide (2.5 mg/kg body weight) on the amount of pulmonary oedema was studied. Pretreatment with methysergide resulted in a 20% decrease in lung weight in thrombin-treated rats. It caused a significant reduction of dilated lymph vessels, and of interstitial and alveolar oedema, as evaluated morphometrically. Methysergide pretreatment did not significantly alter the number of degranulated mast cells. Antiserotonin is thought to exert its effect by lowering the filtration pressure in the pulmonary microcirculation.