Endotracheal Administration of Tolazoline in Hypoxia-Induced Pulmonary Hypertension

Study objective. To compare the pulmonary and systemic vascular responses to intravenously (IV) and endotracheally (ET) administered tolazoline (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 catheterized for continuous physiologic monitoring and cardiac output meassurements using radiolabeled microspheres. After a postoperative stabilization period, the lambs were ventilated with a hypoxic gas mixture which was titrated to increase mean pulmonary artery pressure (MPAP) 30% to 50% above baseline. Each animal was randomly assigned to receive either IV-Tz (2 mg/kg), ET-Tz (4 mg/kg), or ET-saline (Sal, control group). Results. ET-Tz significantly (P < .05) reduced MPAP, PVRI (pulmonary vascular resistance index), MPAP/mean artery pressure (MAP) and PVRI/systemic vascular resistance index (SVRI), but not SVRI. IV-Tz lowered (P < .05) MPAP, PVRI, and PVRI/SVRI but also produced significant reductions in MAP and SVRI while only transiently decreasing MPAP/MAP. MPAP/MAP and PVRI/SVRI ratios were consistently lower in the ET-Tz animals than either the IV-Tz or ET-Sal animals. Conclusions. Our results suggest that ET-Tz produced a more selective pulmonary vascular response than IV-Tz and may warrant further investigation for potential clinical applications.