SELECTIVE PULMONARY VASODILATION AND PULMONARY DISTRIBUTION OF RADIOLABELED HISTAMINE DURING LIQUID VENTILATION (LV) IN HYPOXIC NEWBORN (NB) LAMBS† 2336

Histamine (H) is a selective pulmonary vasodilator in the fetus and NB. During total LV (TLV), significant decreases in pulmonary artery pressure(Ppa) without systemic effects have been reported during hypoxia-induced pulmonary hypertension following intravenous (IV) and pulmonary administration of drug (PAD) delivering equal doses of H, however during partial liquid ventilation (PLV) there were no PAD effects. To test the hypothesis that differences in the homogeneity of drug distribution within the lung contribute to the differences in PAD effects of H during PLV compared to TLV, we compared both the pulmonary and systemic vascular effects and the pulmonary distribution of H following PAD delivery of 0.05 μg/kg as 0.5cc/kg bolus at the beginning of inspiration during PLV and TLV. NB lambs (n=14) were studied(2.5-5.0 kg) during hypoxia (PaO₂:20-35 mm Hg) during both PLV and TLV, using a perfluorochemical (PFC) (LiquiVent®). Ppa and systemic arterial pressure (SAP) were continuously monitored; physiologic pH and normocarbia were maintained. Radiolabeled (³H) histamine was delivered to randomly selected animals in a supine position using PAD delivery during TLV and PLV. Lungs were hung and dried with continuous distending pressure of 30 cm H₂O and sectioned using a standardized matrix method; samples were weighed, digested and radioactivity counted. Pulmonary distribution was assessed by normalizing the radioactivity of each piece (per dry weight) to the average radioactivity of all pieces in ratio form (uniform distribution resulting in a value of one for each piece) and all ratios were expressed in histogram form. During TLV, PAD H decreased Ppa significantly (p<0.02) and SAP did not change. During PLV, PAD H did not change Ppa or SAP. Representative distribution data using PAD during TLV resulted in 48% of pieces having ratio values between 0.8-1.2. Using PAD during PLV resulted in 14% of samples having ratio values between 0.8-1.2. We conclude that PAD delivery of H during TLV is an effective way of achieving pulmonary selective decreases in vascular pressure, due in part to more homogeneous distribution within the lung. We speculate that alternative techniques for drug delivery with liquid ventilation, such as creating a suitable emulsion of drug in PFC liquid for delivery with the initial fill of the lung, may allow improved pulmonary distribution of drug during both PLV and TLV. (Supp in part by Alliance Pharm Comp and Wyeth Pharm)