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.
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