PULMONARY ADMINISTRATION OF VASOACTIVE SUBSTANCES BY PERFLUOROCHEMICAL VENTILATION

Objectives. Therapeutic management of respiratory distress syndrome, p neumonia, and pulmonary hypertension includes delivery of biologically active agents to the neonatal lung. However, mechanical abnormalities of the lung, intrapulmonary shunting, ventilation-perfusion mismatchi ng, and elevated surface tension impede effective systemic or intratra cheal delivery of agents to the lung during conventional gas ventilati on. The objective of this study was to test the hypothesis that perflu orochemical (PFC) liquid ventilation can be used for pulmonary adminis tration of vasoactive drugs (PAD) and to compare these responses to th ose elicited with intravascular (IV) administration during tidal liqui d ventilation. Methods. Cardiovascular responses of 16 preterm and neo natal lambs to randomized doses of acetylcholine, epinephrine, and pri scoline were studied. Physiologic gas exchange and acid-base balance w ere maintained Using previously described tidal liquid ventilation tec hniques. In subgroups of animals, the distribution pattern of carbon 1 - and choline 14-labeled dipalmitoylphosphatidylcholine (C-14-DPPC) in saline and the responses to priscoline after hypoxia-induced pulmonar y hypertension and hypoxemia administered during liquid ventilation we re studied. Results. Dose-response curves for PAD and IV administratio n demonstrated progressive, dose-dependent, cholinergic responses to a cetylcholine (decreased mean systemic arterial pressure [MAP] and hear t rate), sympathomimetic responses to epinephrine (increased MAP and h eart rate), and alpha-adrenergic blockade responses to priscoline (dec reased MAP and mean pulmonary arterial pressure). Compared with IV adm inistration, PAD of priscoline resulted in a significantly greater dec rease in pulmonary relative to systemic arterial pressure; this respon se was potentiated by hypoxia, reduced pulmonary pressures to near nor mal values, and improved oxygenation. The C-14-DPPC in saline was dist ributed relatively homogeneously throughout the lung by PAD, with 80% of the lung pieces receiving amounts of C-14-DPPC with +/-20% of the m ean value. Conclusions This study demonstrates that vasoactive agents can be delivered to the lung directly by PAD during PFC liquid ventila tion. The inherent advantages of this method relate to the physical pr operties of PFC liquid ventilation as a vehicle (respiratory gas solub ility, low surface tension-enhancing distribution, and inertness precl uding interaction) and physiological properties of the lung as an exch anger.