Pulmonary response to free fatty acid intravenous infusion in the rabbit: role of leukotrienes and the effect of prostacyclin.
Intravenous infusion of free fatty acid (FFA) 20 mg.kg-1.min-1 produces pulmonary edema, hypoxemia, hyperventilation and increase in the alveolar surfactant content in rabbits in less than 15 min. We tried to study the role of leukotrienes (LT) and the effects of PGI2 in pulmonary response to FFA. We used Piriprost an inhibitor of LT synthesis or Epoprostenol (Prostacyclin: PGI2) in 4 series of rabbits treated with FFA or its vehicle. Piriprost given as an aerosol (0.1% W/W in THAM) scarcely modified the morphofunctional changes induced by FFA. The only pulmonary effect prevented by Piriprost was the increase in surfactant content (disaturated phosphatidylcholine: DSPC) in broncho-alveolar lavage gluid (BAL). PGI2 administered in a dose of 0.1 micrograms.kg-1.min-1 5 minutes prior to a 15 min infusion of FFA was also unable to prevent most of the effects of FFA on the lung. Only the increase in DSPC in BAL was prevented by PGI2. Some animals received a smaller dose of FFA, because they died earlier. Piriprost, as well as PGI2, shortened the survival time of rabbits treated with FFA. This decrease in the survival rate of animals treated with FFA could account for the lack of increase in DSPC post-FFA. Since other morphofunctional changes induced by FFA were scarcely modified by both Piriprost or PGI2, our results suggest that it is unlikely that either leukotrienes on PGI2 may have a significant effect on pulmonary disturbances induced by FFA.
Arenas
G
G
Departamento de Ciencias Preclínicas, Facultad de Medicina, Universidad de Chile, Santiago.
Del Buono
R
R
Oyarzún
M J
MJ
Donoso
P
P
Quijada
D
D
D000818:Animals; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D015289:Leukotrienes / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011817:Rabbits; D013928:Thromboxane A2 / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D015289:Leukotrienes; D013928:Thromboxane A2; D011464:Epoprostenol; C035296:piriprost