Effect of hyperthermia on uterine and umbilical blood flows in pregnant sheep.

Uterine and umbilical blood flows were measured in pregnant sheep (125-142 days gestation) under normothermic and hyperthermic conditions using the Fick principle with [14C]antipyrine as the indicator. Exposure of the sheep to an ambient temperature of 43 +/- 1 degrees C (25-30% relative humidity) for 8 h increased maternal and fetal core temperatures 1.19 +/- 0.15 and 1.39 +/- 0.12 degrees C respectively. Maternal hyperventilation caused a significant decrease of both maternal and fetal arterial partial pressure of CO2 (Pa,CO2) and increase of arterial pH. Uterine blood flow increased significantly during the hyperthermia (+54.2 +/- 14.1%), the increase being correlated with the magnitude of the decrease of maternal Pa,CO2 (r = -0.84, P < 0.05) but not with the increase of maternal core temperature. The increase of uterine blood flow was not associated with a concomitant increase in the placental clearance of [14C]antipyrine, a result which could arise if the increase of blood flow was non-placental (i.e. did not occur within the cotyledons), or occurred through uterine arteriovenous shunts during the period of heat stress. Hyperthermia was not associated with a significant change of umbilical blood flow, placental transfer of glucose, or fetal glucose uptake. Since the loss of heat from the fetus occurs mainly across the placenta, we speculate that the apparent increase of uterine blood flow during maternal hyperthermia has an adaptive significance by maintaining conductive heat flux in a fetomaternal direction, even though cotyledonary (placental) blood flows did not increase.

Effect of hyperthermia on thyroid structure in the late gestation fetal lamb.

This study examined the effect of hyperthermia in late gestation on fetal thyroid structure. Mild heat stress (increase of ewe's rectal temperature to 40.4 degrees C) caused significant changes of fetal thyroid structure. Intra-follicular colloid area was significantly larger in the heat-stressed group (2,532 +/- 181 microns2) compared to a control group where rectal temperature of the ewe was within the normal range (1,660 +/- 188 microns2; p less than 0.01). Epithelial cell height was significantly reduced (2.5 +/- 0.19 vs. 4.8 +/- 0.26 microns; p less than 0.01). Fetal plasma glucose concentrations were significantly lower in the heat-stressed group (0.7 +/- 0.07 mmol/l) compared to the non-heated group (1.0 +/- 0.11 mmol/l; p less than 0.05). We suggest that the fetal thyroid gland in sheep is responsive to environmental temperature changes and is important in the neuroendocrine regulation of fetal body temperature. Fetal hypoglycaemia may also contribute to the changes in fetal thyroid gland by altering the peripheral utilization of thyroid hormone. Such changes, if prolonged, may contribute to the decreased rate of fetal growth and maturation associated with chronic heat stress in sheep.

Effects of hyperthermia on fetal and maternal plasma prostaglandin concentrations and uterine activity in sheep.

The exposure of pregnant sheep to high ambient temperatures (43 degrees C) for 8 hours, sufficient to significantly elevate maternal and fetal body temperature +2.0 degrees C (p less than 0.001) and +1.9 degrees C (p less than 0.001) respectively, resulted in significant increases in PGE2 plasma concentrations in both the maternal and fetal circulations. Plasma PGF2 alpha concentrations were significantly raised in the fetal circulation but not the maternal during hyperthermia. The increase in prostaglandin concentrations were correlated with the magnitude of the increase in maternal and fetal body temperature. Uterine activity also increased during hyperthermia, probably as a result of the increase in prostaglandin concentrations. We propose that increased synthesis and release of prostaglandins from the uterus and/or placenta is an adaptive response to hyperthermia, and may protect the fetus from the consequences of heat stress.

Developmental changes in hindlimb muscles and diaphragm of sheep.

In this study, plasma thyroxine, contractile and histochemical (adenosinetriphosphatase and NADH) characteristics of soleus (SOL), medial gastrocnemius (MG), and extensor digitorum longus (EDL) were examined in 140-day-gestation fetal sheep and in 2-, 5-, and 30-day-old lambs and adult ewes. Electrophoretic separation of myosin heavy chains was also done on all muscles and the diaphragm. There were no differences in the twitch contraction and relaxation times of MG and EDL at the different ages; in contrast SOL contraction times were significantly shorter in the fetus and newborn than in the adult. Fast glycolytic fibers first appeared in EDL, MG, and diaphragm at 5, 30, and 5 days after birth, respectively. The proportion of slow oxidative fibers decreased after birth and with postnatal development in EDL, whereas they increased in MG and diaphragm. Plasma thyroxine concentrations were higher in the fetus and day-old lambs than in 2-, 5-, and 30-day-old lambs or adult sheep. It is suggested that contractile specialization of the fast-twitch diaphragm, MG, and EDL is largely achieved in utero and is probably mediated by thyroid hormone. In contrast, SOL changed postnatally, probably influenced by the altered neural drive.

Effects of thyroidectomy on development of skeletal muscle in fetal sheep.

The influence of the thyroid gland on the functional and histochemical development of fast- and slow-twitch skeletal muscle of fetal sheep has been studied in euthyroid fetal sheep (n = 6) and athyroid fetuses (n = 4) surgically thyroid-ectomized at 70-75 days of gestation. Two fast-twitch muscles, the medial gastrocnemius and extensor digitorum longus, and the slow-twitch soleus muscle were studied at the fetal age of 140 days gestation. The athyroid fetuses had significantly slower twitch contraction and relaxation times in both the medial gastrocnemius and extensor digitorum longus muscles compared with the euthyroid fetuses. Twitch contraction and relaxation times of the soleus were not different in the two groups. Thyroidectomy resulted in an increase in the proportion of fast (type II) muscle fibers and myosin, as shown histochemically and by gel electrophoresis of heavy-chain myosins. These results indicate that the functional maturation of the fast-twitch muscles of sheep is influenced by the presence of an intact thyroid gland from at least 70 days of gestation. In contrast, the slow-twitch soleus muscle fiber diameter and twitch contraction and relaxation times were not different in the two groups.

Effect of inhibiting prostaglandin synthesis in pregnant sheep with 4-aminoantipyrine under normothermic and hyperthermic conditions.

Infusion of the prostaglandin synthetase inhibitor 4-aminoantipyrine at a rate of 20 mg/min via the fetal tarsal vein during normothermic conditions (ambient temperatures = 24 degrees C) significantly decreased the concentrations of prostaglandins E2 and F2 alpha in maternal and fetal arterial plasma and in uterine and umbilical vein plasma. The infusion was associated with a small but significant rise in fetal temperature and a fall in fetal arterial pH. Respiratory alkalosis developed in fetuses during hyperthermia by raising the ambient temperature to 43 degrees C for 8 hours. In contrast, infusion of 4-aminoantipyrine during hyperthermia produced fetal metabolic acidosis as indicated by a fall in fetal pH and an increase in PaCO2, even though the ewe remained hypocapnic. Four of the 10 fetuses died during or shortly after the 4-aminoantipyrine infusion during hyperthermia. These results indicate that uteroplacental prostaglandin synthesis is essential to allow the fetus to adapt to an increase in body temperature and suggests that prostaglandin synthetase inhibitors should be used with caution during pregnancy.