The effects of NA872 on pulmonary maturation in the fetal lamb and rabbit G. R. VAN PETrEN, PH.D. G.

P.

J. J.

MEARS, PH .D. TAYLOR, M.B., F.R.C.S.(C), M.R.C.O.G.

Calgary'• Alberta, Canada

The effect of fetal administration of NA872, metabolite VIII of Bisolvon, on the lecithin/sphingomyelin (l/S) ratio of ovine tracheal fluid and of its administration to the pregnant doe on the fetal rabbit pulmonary pressure-volume relationship was determined. Intravenous administration of NA872 in the long-term cannulated lamb fetus in a dose of 4 mg. per day from either 120 to 1.25 or 125 to 130 days of gestation produced a significant increase in the L/S ratio. Administration of 4 mg. per kilogram per day to the pregnant doe on days 21 to 24 of gestation resulted in significant enhancement of lung maturation in the 25 day fetal rabbit lung as judged from the pressure-volume relationship; a smaller dose, or the same total dose given over shorter time periods, had no significant effect in the 25 day rabbit fetus. Similarly, 8 mg. per kilogram given to the doe on days 26 and 27 produced no over-all significant effect on the 28 day rabbit fetus, although a seasonal effect was found at this age. (AM. J. 0BSTET. GYNECOL. 130: 35, 1978.)

THE RELATIONSHIP between abnormally high surface tension in lung extracts 1- 4 and low concentrations of phospholipid surfact.ants5 -~ in the respiratory distress syndrome of the neonate, and the observation that adrenal glucocorticoids will enhance the production of phospholipid surfactants9 - 11 in various mammalian species, have led to the successful attempt to prevent respiratory distress of the newborn infant in premature human fetuses by antepartum administration of glucocorticoids to the mother. 12 The relationship between potent glucocorticoids and induction of premature labor. 13 · 14 growth retardation, 15 or diminution of lung/body weight ratio10 is still unclear. In addition, poor results were demonstrated in increasing pulmonary surfactants in babies of mothers with the syndrome of severe hypertension, proteinuria, and fetal growth retardation. 12 In view of these problems and uncertainties regarding the long-

term effects in development following the administration of glucocorticoids, other measures should be sought to reduce the incidence of respiratory distress syndrome. The drug Bisolvon (N-cyclohexyl-N-methyl-(2amino-3, 5-dibromobenzyl)-ammonium chloride] has well-described mucolytic activity and its active metabolite, NA872 (metabolite VIII) 16 (Fig. 1), has been shown in albino mice under conditions of reduced pulmonary surfactant to increase the activity of type II pneumocytes in producing pulmonary surfactant. 17 Preliminary studies in our laboratory and early clinical trials 18 suggested that NA872 might be effective in enhancing fetal pulmonary surfactant production and maturation. This report describes the effects of NA872 on surfactant production in the ovine fetal lung as estimated from the lecithin/sphingomyelin (LIS) ratioH• in tracheal fluid, and on physiologic maturation of the rabbit fetal lung as estimated from pressure volume curves.

From The Divisions of Phnrmacology and Therapeutics, Medical Physiology, and Obstetrics and Gynaecology, Facult~~ of Medi

The effects of NA872 on pulmonary maturation in the fetal lamb and rabbit.

The effects of NA872 on pulmonary maturation in the fetal lamb and rabbit G. R. VAN PETrEN, PH.D. G. P. J. J. MEARS, PH .D. TAYLOR, M.B., F.R.C.S.(...
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