EFFECT OF INTRALIPID ON HYPOXIC AND ANGIOTENSIN-II-INDUCED PULMONARY VASOCONSTRICTION IN THE ISOLATED RAT LUNG

Objective: Lipid infusions are reported to cause hypoxemia by increasing intrapulmonary shunt fraction. However, the mechanism by which they worsen gas exchange is unknown. We hypothesized that a reduction in hypoxic pulmonary vasoconstriction, caused by lipid infusion, could be the cause of increased shunt. Design: A prospective, controlled laboratory study. Setting: A postgraduate teaching hospital laboratory. Subjects: Male Wistar rats weighing 250 to 300 g. Interventions: Four separate series of experiments were performed: a) The pulmonary vasopressor response to angiotensin-II was compared before and after adding either 0.9% sodium chloride (control n = 5) or 20 mu L of Intralipid (n = 8). b) The pulmonary vasopressor response to hypoxia (EIO(2) of 0.3) was compared before and after either 0.9% sodium chloride (control n = 5) or 20 mu L of Intralipid (n = 8). c) 1 mu M of indomethacin was added before either 0.9% sodium chloride (control n = 5) or Intralipid (n = 5) and the hypoxic pulmonary vasoconstriction response was compared. d) 10(-3) ML-monomethyl-n-arginine was added before 20 mu L of Intralipid and the hypoxic pulmonary vasoconstriction response was compared (n = 5). Measurements and Main Results: Changes in pulmonary arterial pressure were measured before and after interventions. Intralipid reduced the angiotensin-II presser response by 36 +/- 3% (p = .005) and the hypoxic pulmonary vaso-constriction response by 50 +/- 2% (p = .0003). This action was not blocked by pretreatment with either indomethacin or L-monomethyl-n-arginine. Conclusions: Intralipid reduces the hypoxic pulmonary vasoconstriction response in the isolated, blood perfused rat lung. This action is nonspecific, as shown by a similar reduction in the pulmonary presser response to angiotensin-II. pharmacologic blockade of prostaglandin release, by indomethacin, and nitric oxide release, by L-monomethyl-n-arginine did not prevent the reduction in hypoxic pulmonary vaso-constriction, thereby suggesting that neither agent mediates the lipid-induced change in pulmonary vasoreactivity.