Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in vasoconstrictor pulmonary hypertension in sheep.
Patients with pulmonary hypertension challenge the anesthesiologist with complex alterations of hemodynamic function. To study the effects of multiple therapeutic interventions, a stable model of pulmonary hypertension in sheep was developed using continuous infusion of the vasoconstrictor U46619, a thromboxane A2-mimetic. The pulmonary and systemic effects of four pulmonary vasodilators (prostaglandin E1, isoproterenol, prostacyclin, and nifedipine) were compared at doses producing equivalent reduction in systemic blood pressure. Although all four drugs decreased pulmonary artery pressure and resistance, distinct differences in drug hemodynamic profiles were found. Prostaglandin E1 and isoproterenol demonstrated the greatest pulmonary specificity, increased cardiac output significantly, and decreased pulmonary vascular resistance. Prostaglandin E1 produced the largest decrease in pulmonary artery pressure (from 31 +/- 1 to 22 +/- 2 mm Hg). Isoproterenol markedly increased heart rate (from 119 +/- 6 to 182 +/- 10 beats/min) and resulted in significant dysrhythmias that necessitated limiting infusion of this drug; isoproterenol did not affect stroke volume. Prostacyclin demonstrated intermediate pulmonary specificity and produced the largest increase in cardiac output (from 1.7 +/- 0.2 to 3.1 +/- 0.3 L/min). Nifedipine exhibited the least pulmonary specificity and was the least effective agent in decreasing pulmonary artery pressure. In this model different pulmonary vasodilators exerted different hemodynamic effects, suggesting that appropriate drug selection for treatment of pulmonary hypertension should depend on baseline heart rate and rhythm, pulmonary artery pressure, systemic artery pressure, arterial oxygenation, and cardiac output.
Prielipp
R C
RC
Department of Anesthesia, Stanford University Medical Center, California.
Rosenthal
M H
MH
Pearl
R G
RG
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D007545:Isoproterenol / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply; D009543:Nifedipine / Q000627:therapeutic use*; D011450:Prostaglandin Endoperoxides, Synthetic; D011651:Pulmonary Artery / Q000187:drug effects; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D011464:Epoprostenol; D000527:Alprostadil; D009543:Nifedipine; D007545:Isoproterenol