Journal of Applied Physiology
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J Appl Physiol 99: 2363-2368, 2005. First published September 1, 2005; doi:10.1152/japplphysiol.00083.2005
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Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation

Brett L. Sandifer,1,3 Kenneth L. Brigham,1,2,3 E. Clinton Lawrence,1,3 David Mottola,4 Chris Cuppels,1,2 and Richard E. Parker1,2

1Division of Pulmonary, Allergy, and Critical Care, 2Center for Translational Research in the Lung, and 3McKelvey Center for Lung Transplantation, Emory University School of Medicine, Atlanta, Georgia; and 4United Therapeutics Corporation, Research Triangle Park, North Carolina

Submitted 24 January 2005 ; accepted in final form 20 July 2005

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostinil on pulmonary and systemic hemodynamics in an unanesthetized sheep model of sustained acute pulmonary hypertension. Acute, stable pulmonary hypertension was induced in instrumented unanesthetized sheep by infusing a PGH2 analog, U-44069. The sheep were then administered identical doses of treprostinil either intravenously or by aerosol. Systemic and pulmonary hemodynamics were recorded during each administration. Both intravenous and aerosol delivery of treprostinil reduced pulmonary vascular resistance and pulmonary arterial pressure, but the effect was significantly greater with aerosol delivery (P < 0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics, whereas intravenous delivery increased heart rate and cardiac output and decreased left atrial pressure and systemic blood pressure. Aerosol delivery of the prostacyclin analog treprostinil has a greater vasodilatory effect in the lung with minimal alterations in systemic hemodynamics compared with intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.

pulmonary hypertension; transcription factor activator protein-1; epoprostenol


Address for reprint requests and other correspondence: R. E. Parker, 615 Michael St., Suite 250, Whitehead Research Bldg., Atlanta, GA 30322 (e-mail: reparke{at}emory.edu)






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