Shortly after birth the newborn's ability to produce additional heat may become critical for survival. The newborn lamb produces heat by shivering in skeletal muscle and nonshivering metabolic activity in brown fat. When cooled in utero, however, fetal thermogenic responses are relatively inactive. The purpose of these experiments is to investigate the factors which allow thermogenesis to become active at birth. We plan to examine the importance of rising levels of tri-iodothyronine (T3) and norepinephrine, the possibility of a placentally-synthetized inhibitor, the possibility of additional oxygen delivery to thermogenic organs by blood flow redistribution, the importance of kinetic factors, and a possible change in sensitivity of thermal receptors. These studies will use the chronically-prepared, unanesthetized fetal sheep. Birth will be simulated in utero by ventilating the lungs with oxygen and snaring the umbilical cord. Thermogenic responses to cooling will be monitored by measuring free fatty acids, glycerol, brown fat temperature, and whole-body oxygen consumption. The effects of exogenous hormones (T3 and beta-agonists), blockers (gallamine and propranolol), metabolic substrates, and cross-circulation between newborn and feta sheep, will be studied. This work relates to an understanding of temperature regulation and heat production in the fetal and newborn period and is thus relevant to clinical management at this time.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD016827-08
Application #
3313975
Study Section
Reproductive Biology Study Section (REB)
Project Start
1982-07-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Loma Linda University
Department
Type
Schools of Medicine
DUNS #
City
Loma Linda
State
CA
Country
United States
Zip Code
92350
Suzuki, S; Power, G G (1999) Role of adenosine in regulation of brain temperature in fetal sheep. Am J Obstet Gynecol 181:681-7
Kubonoya, K; Yoneyama, Y; Sawa, R et al. (1998) Brain temperature and metabolic responses during umbilical cord occlusion in fetal sheep. Pflugers Arch 436:667-72
Power, G G; Bragg, S (1997) Improved method for single-bolus kinetic measurements using a noncleared reference indicator. Am J Physiol 273:R828-32
Kubonoya, K; Power, G G (1997) Plasma adenosine responses during repeated episodes of umbilical cord occlusion. Am J Obstet Gynecol 177:395-401
Sawa, R; Yoneyama, Y; Otsubo, Y et al. (1997) Fetal plasma hypoxanthine level in growth-retarded fetuses before labor. J Clin Endocrinol Metab 82:4028-31
Ishikawa, M; Yoneyama, Y; Power, G G et al. (1996) Maternal theophylline administration and breathing movements in late-gestation human fetuses. Obstet Gynecol 88:973-8
Ball, K T; Gunn, T R; Gluckman, P D et al. (1996) Suppressive action of endogenous adenosine on ovine fetal nonshivering thermogenesis. J Appl Physiol 81:2393-8
Ball, K T; Gunn, T R; Power, G G et al. (1995) A potential role for adenosine in the inhibition of nonshivering thermogenesis in the fetal sheep. Pediatr Res 37:303-9
Yoneyama, Y; Shin, S; Iwasaki, T et al. (1994) Relationship between plasma adenosine concentration and breathing movements in growth-retarded fetuses. Am J Obstet Gynecol 171:701-6
Takeuchi, M; Yoneyama, Y; Power, G G (1994) Role of prostaglandin E2 and prostacyclin in nonshivering thermogenesis during simulated birth in utero. Prostaglandins Leukot Essent Fatty Acids 51:373-80

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