Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock

Background: Cardiac dysfunction during septic shock is well described but t he underlying mechanisms still remain to be resolved. This study was conduc ted to elucidate the involvement of endothelin in cardiac function during e ndotoxin shock by the use of endothelin receptor antagonism. Methods: Anaesthetised and haemodynamically stable landrace pigs received t he nonpeptide mixed endothelin receptor antagonist bosentan, two hours afte r onset of endotoxaemia (n = 7). Cardiopulmonary vascular changes, includin g cardiac index, stroke work index, coronary artery blood flow, rate of cha nge of left ventricular pressure (dp/dt), and arterial and coronary sinus p lasma levels of endothelin-1-like immunoreactivity were compared to a contr ol group only receiving endotoxin (n = 7). Results: Plasma endothelin-1-like immunoreactivity increased threefold in t he control group. Bosentan effectively counteracted the endotoxin induced d ecrease in cardiac index. This was accompanied by a significant reduction o f both right and left ventricular afterload. In addition, coronary artery b lood flow increased and coronary vascular resistance decreased compared to controls. Dp/dt remained unaffected by endothelin receptor antagonism. A fu rther increase in plasma endothelin-1-like immunoreactivity was seen in res ponse to bosentan. Conclusion: These results indicate that the increased endothelin production during endotoxaemia contributes to a depressed cardiac performance and tha t endothelin receptor antagonism may counteract this development. Possible mechanisms for the improved cardiac performance include both a reduction of afterload and enhanced coronary blood flow.