Submitted on January 24, 2005
Accepted on July 20, 2005
Potent Effects of Aerosol Compared to Intravenous Treprostinil on the Pulmonary Circulation
Brett L. Sandifer1*, Kenneth L. Brigham2, E. Clinton Lawrence1, David Mottola3, Chris Cuppels4, and Richard E. Parker4
1 Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA; McKelvey Center for Lung Transplantation, Emory University, Atlanta, GA, USA
2 Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA; Center for Translational Research in the Lung, Emory University, Atlanta, GA, USA; McKelvey Center for Lung Transplantation, Emory University, Atlanta, GA, USA
3 United Therapeutics Corp., Research Triangle Park, NC, USA
4 Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA; Center for Translational Research in the Lung, Emory University, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: blsandifer{at}yahoo.com.
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 versus 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, U44069. 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 artery pressure but the effect was significantly greater with aerosol delivery (p<0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics while 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 to intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.
