Lung Vascular Effects of Lipid Infusion in Awake Lambs

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Abstract
Numerous reports have shown that intravascular lipid infusion may cause pulmonary dysfunction in a variety of species, including humans. To determine the effects of parenteral lipid on neonatal pulmonary hemodynamics, lung fluid filtration, and respiratory gas exchange, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, lymph and plasma protein concentrations, and partial pressures of oxygen and carbon dioxide in arterial blood of 11 awake chronically catheterized lambs that received a 2-3 h control infusion of glucosesaline solution followed by Intralipid at a dose of 67.5,125, or 250 (mg/h)/kg body weight for 6 h. Intralipid caused an acute dose-dependent increase in pulmonary arterial pressure, with no significant change in cardiac output or left atrial pressure. The pulmonary hypertension, which lasted for at least 2 h, was accompanied by a >50% increase in lung lymph flow and a significant decrease in lymph protein concentration relative to plasma protein concentration. Pulmonary artery pressure gradually decreased to control values during the final 2 h of lipid infusion, but lymph flow remained 35% above control and lymph protein concentration remained low. Lipid infusion also was associated with a modest decrease in PaO2. Both arterial and venous administration of lipid gave similar results. In separate studies, lipid infusion caused a significant increase in plasma concentrations of thromboxane B2, the stable metabolite of thromboxane A2, without affecting plasma concentrations of 6-keto prostaglandin F1a, the stable metabolite of prostacyclin. Pretreatment with imidazole, which attenuated the lipid-induced increase in thromboxane B2 concentration, completely blocked the pulmonary hemodynamic response to lipid. Moreover, in the presence of imidazole there was no significant change in any of the other measured variables during lipid infusion. These results suggest that 1) lipid infusion causes a sustained increase in pulmonary microvascular pressure, most likely from constriction of lung vessels distal to sites of fluid exchange; and 2) thromboxane A2 is at least partly responsible for these changes.