The Central Effects of Thyrotropin-Releasing Hormone on the Breathing Movements and Electrocortical Activity of the Fetal Sheep

Abstract

ABSTRACT. The fetal respiratory and electrocortical effects of thyrotropin-releasing hormone (TRH) administered into the lateral cerebral ventricles, have been investigated in chronically catheterized unanesthetized fetal sheep at 125-140 days of gestation. Stimulatory effects on fetal breathing movements were seen at doses as low as a lug bolus. TRH given as a 5-pg bolus followed by a 10 pg/ h infusion for 2 h induced a rapid switch to significantly faster, deeper, and continuous fetal breathing movements, while the electrocorticogram remained episodic. Fetal breathing movements did not stop during hypoxia. TRH given as a 2-pg bolus followed by a 4 pg/h infusion or as a 5-pg bolus followed by a 5 pg/h infusion induced the same stimulation of FBMs, but breathing essentially remained episodic, state related and inhibited by hypoxia. As hypothermia presumably induces a surge in TRH secretion at birth it is possible that TRH has some role in the switch from fetal to postnatal breathing patterns. sheep (Romney-Suffolk cross) at 120-130 days gestation under maternal halothane/oxygen anaesthesia, using sterile techniques. Catheters were implanted into a carotid artery, a jugular vein, the trachea, and the amniotic sac. Stainless steel electrodes were implanted bilaterally onto the parietal dura and the nuchal and diaphragm muscles (14). A lateral cerebral ventricle cannula was implanted as previously described (1 3). Fetal catheters were exteriorized through the maternal flank. Vascular catheters were also implanted into a maternal pedal artery and vein. These catheters were exteriorized on the maternal flank close to the fetal catheters. The postoperative care of the ewe and maintenance of the CSF catheter have been described previously (1 3). EXPERIMENTAL PROCEDURESExperiments were conducted at least 5 days postoperatively and were canied out only when the fetal arterial PO2 was higher than 18.0 mm Hg and fetal arterial pH was more than 7.32. Only one experiment a day was conducted. The gestational age at which fetuses were studied ranged between 125 to 140 days.All infusions were performed using a CSF pH, after dissolution of TRH, of 7.34-7.38 (13). The CSF catheter dead-space was 0.7 ml. The control experiments consisted of a 1.4 ml bolus followed by a 1.0 ml/h infusion of artificial CSF for 2 h, over a pH range of 7.34-7.38. The control for bolus alone experiments was the administration of a 1.4-ml bolus of CSF as previously described (1 3). These experiments were performed inseven fetbses. As an additional check the lateral ventricle cannula was flushed with filtered artificial CSF 1-2 h before each experiment.TRH (L-pyroglutamyl-L-histidyl-L-prolinamide Sigma Chem-TRH has been found to exist throughout the nervous system ical CO.) Was diluted appropriately with artificial CSF and the including areas of the brain stem known to contain nuclei PH checked and adjusted if necessary by bubbling 5% C02/95% involved in respiratory control (1-3). TRH administered ten-Oz gas mixture through the solution. This solution re...

High Sensitivity to Neuromodulator-Activated Signaling Pathways at Physiological [K+] of Confocally Imaged Respiratory Center Neurons in On-Line-Calibrated Newborn Rat Brainstem Slices

“…Regarding the mechanism of action, TRH targets G ␣q -protein-linked receptors that may directly block twopore-domain K ϩ channels (Chen et al, 2006;Töpert et al, 1998) that are proposed to contribute to respiratory rhythm generation (Ballanyi et al, 1999;Smith et al, 2000). While the respiratory stimulatory action of TRH is established (Hedner et al, 1983; Bennet et al, 1988), we report for the first time that DHPG-mediated activation of metabotropic glutamate receptors induces PBC rhythm. Locomotor networks in neonatal rats (Nistri et al, 2006) and respiratory networks in lampreys (Bongianni et al, 2002) are similarly sensitive to the agent.…”

Effects of Antenatal Thyrotropin-Releasing Hormone on Fetal Heart Rate and Breathing Movements

“…However, those observations were made 45 min from the start (15 min from the end) of TRH infusion, and changes persisted in some fetuses for up to 8 h. Although the exact pharmacokinetics and dynamics of TRH remain to be determined, it seems unlikely, given the extremely short half-life of TRH, that these effects were the direct result of a rise in fetal TRH levels. Notwithstanding this, sheep studies indicate that TRH-induced FBM changes persist for at least 15 min after intravenous injection to the fetus, and for 25-43 min after intracisternal injection in the fetus [8,9].…”

Influence of Thyrotrophin-Releasing Hormone on Thermoregulation in Newborn Lambs

“…Shivering in young guinea-pigs is determined by the temperature gradient between the cervical vertebral canal and skin, rather than hypothalamic temperature [14]. It is not known if a similar situation occurs in the newborn lamb, although TRH administration into the lateral cerebral ventricles of fetal lambs stimulates breathing [8], an adaptation that can be accompanied by shivering following skin surface cooling [15]. A response of this type could explain why in the current study TRH administration to caesarean section delivered lambs stimulated both shivering and ventilation.…”

“…Thyrotrophin-releasing hormone (TRH) content in the hypothalamus peaks close to term [7] and an increase in the rate of TRH secretion during parturition has been proposed to provide an important stimulus necessary for the establishment of continuous breathing after birth [8]. A delay or reduced rate of TRH release following birth by caesarean section due to the absence of physical stress associated with vaginal delivery could be a primary factor contributing to low plasma thyroid hormone concentrations in caesarean section delivered lambs [3].…”