The specific aims of this project are to define: 1) the role of circulating vasoactive substances (prostaglandins, other arachidonic acid metabolites, angiotensin II, catecholamines and vasopressin) in the physiological and pharmacological regulation of the perinatal pulmonary circulation, and 2) factors which regulate lung liquid formation and reabsorption in fetal animals prior to birth. An isolated (in-situ), pump perfused, lower left lung preparation in anesthetized, exteriorized fetal goats and sheep will be used to study regulation of blood flow to the lungs. Both acute and chronic studies will be carried out on fetal goats and sheep, respectively, to determine changes in lung fluid formation (using an impermeant tracer technique) and composition. The long term objectives of these studies are to provide a better understanding of the factors which contribute to: 1) regulation of the perinatal 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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Human Embryology and Development Subcommittee 2 (HED)
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University of Florida
Schools of Medicine
United States
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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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