Mechanism of bronchoconstriction produced by thromboemboli in dogs

¹ Medical Research Department, Yamins Research Laboratory, Beth Israel Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts

In 19 dogs, the release of autologous venous thrombi to the lungs resulted in bronchoconstriction, with a rapid rise in the total lung resistance and a fall in the lung compliance. The respiratory rate and arterial-alveolar CO₂ tension difference also increased significantly. The administration of either heparin or a 5-HT antagonist completely prevented the bronchoconstriction, without affecting either the respiratory rate or arterial-alveolar CO₂ tension difference. Bronchoconstriction resulting from direct 5-HT infusion was not prevented by heparin, nor was the contraction of an isolated rat uterus in response to 5-HT. However, 5-HT was not released from canine platelets by thrombin in vitro, in the presence of heparin. The evidence suggests that bronchoconstriction in the dog due to autologous pulmonary emboli results from thrombin-induced 5-HT release, and that heparin, by its antithrombin action, prevents this release.

Key Words: heparin • pulmonary emboli • heparin prevents bronchoconstriction • 5-HT-induced bronchoconstriction • mechanism of bronchoconstriction in pulmonary emboli • role of heparin in preventing bronchoconstriction • heparin and 5-HT • pulmonary emboli and bronchoconstriction

Submitted on October 18, 1963

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