The Hemodynamic Effects of Endothelin Receptor Antagonism During a Venous Air Infusion in Dogs

Publisher Website
Google Scholar
Abstract
Endothelin (ET) is involved in the humoral component of the vasoconstriction during pulmonary embolism. We examined the effects of selective ET receptor antag- onists on the hemodynamic and respiratory changes and on serum thromboxane B2 (TXB2) levels, during a continuous venous air infusion (VAI) in anesthetized mongrel dogs. The VAI (0.2 mL z kg21 z min21) was initiated 5 min after an injection of saline (controls, n 5 7), 1 mmol of the selective ETA receptor antagonist JKC- 301 (group A, n 5 6), or 1 mmol of the selective ETB receptor antagonist BQ-788 (group B, n 5 6). Hemody- namic evaluation was performed every 15 min of VAI, and blood samples were drawn for blood gas analysis and TXB2 determinations. The increase in pulmonary perfusion pressure after 30 min of VAI was attenuated in Group A compared with the controls and Group B (Group A 5 7 6 1 mm Hg; Group B 5 16 6 1m m Hg; controls 5 14 6 1m m Hg;P , 0.05). Pulmonary vascu- lar resistance showed a similar behavior. TXB2 concen- trations increased after 60 min of VAI in the controls and in Group B, but not in Group A (controls 5 48%; Group B 5 104%; Group A 5 18%; P , 0.05 for controls and Group B). Similar decreases in Pao2 and Sao2 were observed in the three groups. We conclude that antago- nism of ETA receptors attenuates the hemodynamic changes and blunts the increase in thromboxane A2 production during a VAI in dogs. Implications: We evaluated the effects of endothelin receptor antagonists during a venous air infusion in dogs. EndothelinA receptor antagonism attenuated the hemodynamic changes and blunted the increase in thromboxane A2 production in this setting.