Hemodynamic effects of diltiazem during vasoconstrictor pulmonary hypertension in sheep

Calcium channel blockers have been effective as pulmonary vasodilators in patients with pulmonary hypertension. The current study therefore compared the effects of prostaglandin E1, an effective pulmonary vasodilator, with the effects of the water-soluble calcium channel blocker diltiazem during pulmonary hypertension in sheep. Pulmonary hypertension was produced by continuous intravenous administration of U46619 to halothane-anesthetized sheep. Prostaglandin E1 decreased pulmonary artery pressure 29%, decreased pulmonary vascular resistance (Rp) 57%, and did not affect the ratio of pulmonary to systemic vascular resistance (Rp/Rs). Diltiazem decreased pulmonary artery pressure 15%, decreased Rp 50%, and did not affect Rp/Rs. When 0.33 mL/kg polyethylene glycol-ethanol vehicle (the vehicle used for nifedipine administration in a prior study) was administered during diltiazem infusion, pulmonary artery pressure increased 19%, Rp increased 72%, and Rp/Rs increased 29%. These results indicate that diltiazem is an effective pulmonary vasodilator and suggest that the previously reported unfavorable results of nifedipine may have been due to the vehicle used for nifedipine administration.