Effects of imidazole and indomethacin on fluid balance in isolated sheep lungs

G. A. Patterson, P. Rock, W. A. Mitzner, N. F. Adkinson, J. T. Sylvester

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11 Scopus citations


We determined the effects of extracorporeal perfusion with a constant flow (75 ml.min-1.kg-1) of autologous blood on hemodynamics and fluid balance in sheep lungs isolated in situ. After 5 min, perfusate leukocyte and platelet counts fell by two-thirds. Pulmonary arterial pressure (Ppa) increased to a maximum of 32.0 ± 3.4 Torr at 30 min and thereafter fell. Lung lymph flow (Q̇(L)), measured from the superior thoracic duct, and perfusate thromboxane B2 (TXB2) concentrations followed similar time courses but lagged behind Ppa, reaching maxima of 4.1 ± 1.2 ml/h and 2.22 ± 0.02 ng/ml at 60 min. Lung weight gain, measured as the opposite of the weight change of the extracorporeal reservoir, and perfusate 6-ketoprostaglandin F(1α) (6-keto-PGF(1α)) concentration increased rapidly during the first 60 min and then more gradually. After 210 min, weight gain was 224 ± 40 g and 6-keto-PGF(1α) concentration, 4.99 ± 0.01 ng/ml. The ratio of lymph to plasma oncotic pressure (π(L)/π(P)) at 30 min was 0.61 ± 0.06 and did not change significantly. Imidazole (5 mM) reduced the changes in TXB2, Ppa, Q̇(L) and weight and platelet count but did not alter 6-keto-PGF(1α) π(L)/π(P), or leukocyte count. Indomethacin (0.056 mM) reduced TXB2, 6-keto-PGF(1α), and the early increases in weight, Ppa, and Q̇(L) but did not alter the time courses of leukocyte or platelet counts. Late in perfusion, however, Ppa and Q̇(L) were greater than in either untreated or imidazole-treated lungs. These results suggest that perfusion of sheep lungs with autologous blood caused release of 1) thromboxane, which caused an early transient vasoconstriction with secondary hypertension and edema and 2) prostacyclin, which inhibited both the early thromboxane-mediated vasconstriction and a late occurring vasoconstriction mediated by an unknown mechanism.

Original languageEnglish
Pages (from-to)892-898
Number of pages7
JournalJournal of Applied Physiology
Issue number3
StatePublished - Aug 28 1985


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