Short-term Hemodynamic Effects of Endothelin Receptor Blockade in Dogs With Chronic Heart Failure

Background Plasma endothelin levels are increased in heart failure and may contribute to the increased peripheral vasoconstriction that characterizes this disease state. In the present study, we examined the effects of intravenous bosentan, a nonpeptide, competitive endothelin-1 receptor antagonist, on hemodynamics in dogs with chronic heart failure. Methods and Results Chronic heart failure was produced in 11 dogs by multiple sequential intracoronary microembolization. At the time of study, left ventricular (LV) ejection fraction was 25±2%. Hemodynamic and echocardiographic measurements were made at baseline and at 15, 30, and 60 minutes after a bolus injection of bosentan (10 mg/kg). Bosentan had no significant effect on heart rate or mean aortic blood pressure. At 60 minutes, bosentan reduced LV end-diastolic pressure (17±2 versus 11±2 mm Hg; P<.05) and systemic vascular resistance (3891±379 versus 3071±346 dyne·s·cm−5; P<.05) compared with baseline and increased cardiac output (2.63±0.29 versus 3.33±0...