Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model

Objective: To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation. Design: Prospective, controlled animal study. Setting: University-affiliated research laboratory. Subjects: Thirteen fasted, anesthetized, mechanically ventilated landrace pigs. Measurements and Main Results: Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco₂ gap), and jejunal mucosal oxygenation (tPo₂) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelin_A/endothelin_B antagonist tezosentan at 1 mg·kg^-1·hr^-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco₂ gap increased. The change in tPo₂ failed to gain statistical significance (p = .08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo₂ above baseline, and decreased Pco₂ gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade. Conclusions: Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.