CARDIOPULMONARY DYSFUNCTION DURING PORCINE ENDOTOXIN-SHOCK IS EFFECTIVELY COUNTERACTED BY THE ENDOTHELIN RECEPTOR ANTAGONIST BOSENTAN

In a porcine endotoxin shock model, the mixed nonpeptide endothelin re ceptor antagonist bosentan was administered 2 h after onset of endotox emia (n = 8). Cardiopulmonary vascular changes, oxygen-related variabl es, and plasma levels of endothelin-1-like immunoreactivity were compa red with a control group that received only endotoxin (n = 8). Bosenta n abolished the progressive increase in mean pulmonary artery pressure and pulmonary vascular resistance seen in controls. Possible mechanis ms include blockade of vasoconstrictive endothelin receptors, and a le sser degree of edema and inflammation indicated by less alveolar prote in and a lower inflammatory cell count observed in bronchoalveolar lav age. Further, bosentan restored cardiac index to the pre-endotoxin lev el by an increase in stroke volume index, improved systemic oxygen del ivery, and acid base balance. Because mean arterial blood pressure was unaffected, bosentan reduced systemic vascular resistance. Endotoxemi a resulted in an increase in tumor necrosis factor-alpha and endotheli n-1-like immunoreactivity plasma levels, the latter being further incr eased by bosentan. In conclusion, in porcine endotoxemia, treatment wi th the endothelin receptor antagonist bosentan, administered during fu lminate shock, abolished pulmonary hypertension and restored cardiac i ndex. These findings suggest that bosentan could be an effective treat ment for reversing a deteriorated cardiopulmonary state during septic shock.