title: PGI2 aerosol versus nitric oxide for selective pulmonary vasodilation in hypoxic pulmonary vasoconstriction.
abstract: Intravenous prostacyclin (PGI2) is a potent pulmonary vasodilator in pulmonary hypertension. However, dose-dependent systemic vasodilation, an increase in intrapulmonary shunt and hypoxemia limit its clinical application. Recently, inhaled nitric oxide (NO) has been reported to elicit selective pulmonary vasodilation, but its clinical use is restricted by its potential toxicity; furthermore, the feasibility of NO application in clinical practice seems difficult. Therefore, we investigated the effects of PGI2 aerosol on pulmonary and systemic circulation and compared the hemodynamic effects to those of inhaled NO. In 6 dogs, ventilation with a hypoxic gas mixture (FiO2 0.09-0.11) increased pulmonary vascular resistance (PVR) by 196% (HPV). Aerosolization of a PGI2 solution at a concentration of 430 ng/ml reduced hypoxia-induced increase of pulmonary artery pressure by 48% and PVR by 52% within 6-10 min without systemic vasodilation. The administered dose of PGI2 was 0.87 +/- 0.26 ng/kg/min. In 2 dogs, doubling the PGI2 concentration (860 ng/ml) did not enhance the vasodilatory effect. After termination of PGI2 inhalation, HPV was restored within 10-15 min. Inhaled NO (50 ppm) decreased the HPV-induced increase in PAP by 76% and in PVR by 73% within 5-10 min. Clinically relevant systemic vasodilation was not observed. It is concluded that inhalation of aerosolized PGI2 leads to selective pulmonary vasodilation in hypoxia-induced pulmonary hypertension. Aerosolized PGI2 at a concentration of 430 ng/ml was less potent than NO (50 ppm). However, due to the lack of known toxicity and its uncomplicated mode of application, inhaled PGI2 may be one alternative to inhaled NO in the treatment of acute pulmonary hypertension.
authors.affiliation: Institute of Anaesthesiology, University of Munich, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Welte
authors.forename: B
authors.initials: B
authors.lastname: Zwissler
authors.forename: H
authors.initials: H
authors.lastname: Habazettl
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000633:toxicity; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000336:Aerosols; D009569:Nitric Oxide; D011464:Epoprostenol