Indomethacin inhibition of intralipid-induced lung dysfunction

Intralipid-related pulmonary alterations have been attributed to hyperlipemia. To better quantitate and explain these alterations, Intralipid (0.4 gm/kg over one hour) was infused into three groups of rabbits and saline into a fourth group. Group I had normal lung function; Groups II-IV were pretreated with oleic acid and Group III also received indomethacin. Serum triglyceride (TG) levels, arterial (a) and end-tidal (A) PC0₂ and P0₂ were measured at baseline and then hourly for six hours. There was no ventilatory deterioration in Group I despite a peak TG level of 638 mg/dl. In Group II there was an Intralipid-related Pa0₂ decrease of 11–13 mmHg(p < .01)and aΔ AaP0₂ increase of 16 mm Hg (p < .O1); both returned to baseline without significant TG normalization. Since indomethacin prevented these Pa0₂ and Δ AaP0₂ changes despite a significant TG increase, the effects of Intralipid appear not to be TG-related but rather to be related to PG-mediated alterations in pulmonary vasomotor tone. Our results are most consistent with a net increase in vasodilating prostaglandins and resultant hypoxemia secondary to unblocking of baseline hypoxic vasoconstriction.