Intralipid effect on normal and hypoxic remodeled rat pulmonary vasculature

Intralipid (IL) infusion has been associated with pulmonary vasoconstriction and decreased oxygenation and may worsen preexisting pulmonary vascular changes. To investigate this, we infused IL or 0.9% saline for 1 wk in normal Sprague-Dawley rats and in rats with vascular changes induced by a previous 2-wk exposure to chronic hypobaric hypoxia (air at 380 mmHg). At postmortem we quantitatively evaluated arterial changes in the left lung by light microscopy and alterations in endothelial cells in the right lung by electron microscopy. In rats maintained in room air, 1-wk IL infusion resulted in extension of muscle into alveolar wall and duct arteries (P less than 0.001 for both), medial hypertrophy of arteries 50-99 microns external diameter (P less than 0.01), reduced arterial density (P less than 0.05), and an increase in volume density of endothelial smooth endoplasmic reticulum (P less than 0.05). In post-hypoxia rats, however, IL infusion did not induce further progression of the more severe arterial and endothelial changes observed. To determine whether IL-associated vascular abnormalities may be related to vasoconstriction, different rats were instrumented under pentobarbital sodium anesthesia with indwelling cardiovascular catheters and, 2 days later, with the animals fully conscious, the hemodynamic response assessed. An acute 15-min IL infusion caused a significant increase in pulmonary artery pressure and mild hypoxemia (P less than 0.05 for both) in room air rats but not in the posthypoxia group. This response was not, however, sustained over a 2-day IL infusion. Thus IL induces pulmonary vascular abnormalities that do not appear to be related to vasoconstriction or hypoxemia. We speculate that differences in endothelial metabolism of IL in room air and posthypoxia rats may explain the lack of IL-related abnormalities in the latter group.