ENDOTRACHEAL ADMINISTRATION OF TOLAZOLINE IN HYPOXIA-INDUCED PULMONARY-HYPERTENSION

Study objective. To compare the pulmonary and systemic vascular respon ses to intravenously (IV) and endotracheally (ET) administered tolazol ine (Tz) in newborn lambs with hypoxia-induced pulmonary hypertension. Design. Randomized, controlled study design. Methods. Twenty lambs, 2 to 7 days of age, were anesthetized, intubated, and surgically cathet erized for continuous physiologic monitoring and cardiac output measur ements using radiolabeled microspheres. After a postoperative stabiliz ation period, the lambs were ventilated with a hypoxic gas mixture whi ch was titrated to increase mean pulmonary artery pressure (MPAP) 30% to 50% above baseline. Each animal was randomly assigned to receive ei ther IV-Tz (2 mg/kg), ET-Tz (4 mg/kg), or ET-saline (Sal, control grou p). Results. ET-Tz significantly (P < .05) reduced MPAP, PVRI (pulmona ry vascular resistance index), MPAP/mean artery pressure (MAP) and PVR I/systemic vascular resistance index (SVRI), but not SVRI. IV-Tz lower ed (P < .05) MPAP, PVRI, and PVRI/SVRI but also produced significant r eductions in MAP and SVRI while only transiently decreasing MPAP/MAP. MPAP/MAP and PVRI/SVRI ratios were consistently lower in the ET-Tz ani mals than either the IV-Tz or ET-Sal animals. Conclusions. Our results suggest that ET-Tz produced a more selective pulmonary vascular respo nse than IV-Tz and may warrant further investigation for potential cli nical applications.