The general aims of this project are to define: 1) the role of vasoactive substances in the physiological and pharmacological control of the pulmonary circulation; and 2) the factors involved in regulating the formation and reabsorption of lung liquid in fetal lambs. An isolated (in-situ), pump perfused, lower left lung preparation in anesthetized, exteriorized fetal sheep will be used to study regulation of blood flow to the lungs. Acute studies will consider the interaction of non-eicosanoid vasoactive substances and metabolites of the arachidonic acid cascade on the pulmonary circulation. Evaluation will be made of the role of leukotrienes in modulating the normally high fetal pulmonary vascular tone. Acute studies will be carried out to measure the permeability of pulmonary epithelium to leukotrienes and to quantify production of leukotrienes in fetal lung liquid, lymph and blood during and following prolonged hypoxia. Also the interaction of the thyroid gland, AVP and epinephrine in lung liquid secretion and reabsorption in the near term fetus will be evaluated. The long-term objectives of these studies are to provide a better understanding of the factors which contribute to: 1) regulation of the pulmonary circulation, and 2) adaptations which must occur in the transition from liquid to air breathing at birth. Knowledge of normal and altered mechanisms of control of the pulmonary circulation and lung liquid formation, should be of considerable clinical value in understanding disturbances which may occur in the pulmonary circulation during the perinatal period.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL010834-22
Application #
3334380
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1978-12-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
22
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Cassin, S; Perks, A M (2002) Estimation of lung liquid production in fetal sheep with blue dye dextran and radioiodinated serum albumin. J Appl Physiol 92:1531-8
Kabbani, M S; Cassin, S (1998) The effects of cGMP on fetal sheep pulmonary blood flow and lung liquid production. Pediatr Res 43:325-30
Beierle, E A; Langham Jr, M R; Cassin, S (1996) In utero lung growth of fetal sheep with diaphragmatic hernia and tracheal stenosis. J Pediatr Surg 31:141-6;discussion 146-7
Matalon, S; DeMarco, V; Haddad, I Y et al. (1996) Inhaled nitric oxide injures the pulmonary surfactant system of lambs in vivo. Am J Physiol 270:L273-80
Skimming, J W; DeMarco, V G; Kadowitz, P J et al. (1996) Effects of zaprinast and dissolved nitric oxide on the pulmonary circulation of fetal sheep. Pediatr Res 39:223-8
Tessier, G J; Lester, G D; Langham, M R et al. (1996) Ion transport properties of fetal sheep alveolar epithelial cells in monolayer culture. Am J Physiol 270:L1008-16
Skimming, J W; DeMarco, V G; Cassin, S (1995) The effects of nitric oxide inhalation on the pulmonary circulation of preterm lambs. Pediatr Res 37:35-40
Cassin, S; DeMarco, V; Perks, A M et al. (1994) Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction. J Appl Physiol 77:1445-50
Cassin, S; Perks, A M (1993) Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid secretion. J Appl Physiol 75:1925-9
Davis, T A; Gause, G; Perks, A M et al. (1992) Effects of intravenous saline infusion on fetal ovine lung liquid secretion. Am J Physiol 262:R1117-20

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