Intact Fetal Lambs Research Articles

Cardiovascular effects of dynorphin A-(1-13) and arginine vasopressin in fetal lambs

The cardiovascular effects of the kappa-opioid receptor agonist, dynorphin A-(1-13) (D13), were compared with those of arginine vasopressin (AVP) in intact and bilaterally vagotomized (VGX) fetal lambs. Intravenous injection of AVP (114 ng/kg) produced a significant rise in mean arterial pressure (MAP) lasting 15-20 min in both intact and VGX lambs. AVP produced a bradycardia in intact fetuses concurrently with the MAP response and had no effect on heart rate (HR) in VGX fetuses. D13 (500 micrograms/kg) also produced significant increases in MAP in intact and VGX fetuses that lasted 45-60 min. D13 produced a bradycardia in intact fetal lambs but, unlike AVP, significantly increased HR in VGX fetuses. HR responses to D13 had time courses similar to MAP responses in both intact and VGX fetal lambs. Pretreatment with a vasopressin V1-receptor antagonist significantly attenuated pressor responses to AVP in both treatment groups and to D13 in intact fetuses and abolished the D13 pressor response in VGX fetuses. The antagonist also completely blocked HR responses to AVP in intact and to D13 in VGX fetuses and attenuated the D13 HR response in intact fetuses. Therefore the effects of D13 on ovine fetal cardiovascular function appear to be mediated in part through AVP pathways. D13 also appears to have a positive chronotropic effect on the heart that is normally masked by inhibitory vagal activity.

The partial association of uterine contractions with changes in electrocortical activity, breathing, and PaO2, in the fetal lamb: Effects of brain stem section

In intact fetal lambs near term there was a statistically significant relation between regular small uterine contractions and a change to high-voltage fetal electrocortical activity (excess above chance 15%) or arrest of breathing (excess 12%). Isocapnic hypoxia also arrested fetal breathing. After brain stem transection there was no relation between uterine contractions and the fetal electrocortical activity, but isocapnic hypoxia increased the rate and depth of fetal breathing. Similarly uterine contractions were to a small extent associated with the initiation of fetal breathing movements which continued for about as long as the contraction. We conclude that the occasional effects of uterine contractions are consistent with diminished fetal cranial oxygen supply.

The central control of fetal breathing and skeletal muscle movements.

Breathing movements in the sheep fetus have been observed from a gestational age of about 40 days. From 95 to 115 days fetal breathing movements are almost continuous, interrupted by apnoea rarely exceeding 2 min. From 115 days until term (about 147 days) breathing and movements of the trunk and limbs are episodic. Breathing normally occurs only during rapid-eye-movement sleep as identified by low-voltage cortical electrical activity. Active movements of the neck muscles occur predominantly in high-voltage electrocortical activity. Hypercapnia or acid cerebrospinal fluid perfusion cause an increase in the regularity and depth of breathing when present, and recruit intercostal and laryngeal abductor activity. Isocapnic hypoxia, however, in contrast to the hyperventilation seen postnatally, causes arrest of fetal breathing movements. This effect is due to a central inhibition. Section of the brain stem, from the caudal hypothalamus rostrally, causes dissociation of fetal breathing movements and electrocortical activity into independent rhythms. Section of the brain stem caudally, in the upper pons or at the inferior colliculus, also causes a dissociation of electrocortical activity from breathing movements, which become almost continuous. Isocapnic hypoxia causes an increase in the rate and depth of breathing movements. It is concluded that the arrest of breathing in intact fetal lambs is not due to a direct effect on the respiratory centre in the medulla. The lumbar polysynaptic flexor reflex response becomes episodic after 115 days gestation but, in contrast to fetal breathing movements, is enhanced during high-voltage electrocortical activity. Isocapnic hypoxia arrests movements of the fetal limbs and trunk and inhibits the lumbar flexor reflex. This inhibition of the reflex is prevented by section of the spinal cord at T12, but persists after section of the brain stem in the upper pons. It is attributed to an action on the medulla, independent of the systemic arterial chemoreceptors. Small doses of pentobarbitone (5 mg/kg) cause arrest of fetal breathing movements by a suprapontine mechanism, abolished by brain stem transection, and inhibition of the lumbar flexor reflex by an action on the spinal cord, persisting after transection at T12. Inhibitors of prostaglandin synthetase (indomethacin, meclofenamate or aspirin) induce continuous fetal breathing movements, while prostaglandin E2 arrests fetal breathing. The site of action is on the medulla, as shown by section of the brain stem and of afferents from the systemic arterial chemoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Breathing in fetal lambs: the effect of brain stem section.

The effects of section of the brain stem caudally (through the upper pons or mid-collicular) or rostrally (through the caudal hypothalamus or anterior commissure-suprachiasmatic nucleus) were studied in fetal lambs from 118 days gestation, after recovery in utero. In lambs sectioned caudally, breathing movements and electrocortical activity were dissociated. After some days recovery breathing tended to become continuous, with an abnormal prolongation of inspiratory time. Isocapnic hypoxia caused an increase in the rate and amplitude of breathing. After carotid denervation hypoxia still caused an increase in the amplitude of breathing. In lambs sectioned rostrally, there was also dissociation between breathing movements and electrocortical activity. Breathing remained episodic, with an incidence similar to that of intact fetal lambs. In two lambs after 10 days of recovery the breathing and electrocortical rhythms returned, from time to time, to their normal phasic relationship. Isocapnic hypoxia caused a diminution or arrest of breathing, as in intact lambs. The cardiovascular effects of transection were examined. Baroreflex sensitivity was normal in those lambs sectioned caudally and enhanced in those sectioned rostrally. It is concluded first that as a result of rostral section, independent episodic rhythms of fetal breathing and electrocortical activity can be dissociated. Secondly, moderate isocapnic hypoxia causes arrest of fetal breathing indirectly, requiring the integrity of a suprapontine mechanism. And thirdly, after caudal section of the brain stem, hypoxia causes enhancement of fetal breathing efforts, independently of the carotid chemoreceptors. Possible mechanisms are discussed.

Pulmonary vascular response to prostacyclin in fetal lambs

Eighteen prostacyclin injections (19.4±1.5 μg/kg) were performed in five chronically instrumented, intact fetal lambs in order to study the effects on pulmonary blood flow. These resulted in a brief period of bradycardia followed by a more prolonged period of increased pulmonary blood flow. In this latter phase, pulmonary blood flow increased from a baseline value of 49±4 ml/(kg min) to 122±10 ml/(kg min). Systolic/diastolic pulmonary arterial pressure simultaneously fell from 73±2 48±1 to 68±2 42±1 mm Hg. Flow through the ductus arteriosus was unchanged and right ventricular output increased to account for the increased pulmonary blood flow. Thus, prostacyclin causes pulmonary vasodilation in intact fetal lambs and may participate in the control of fetal pulmonary blood flow and the circulatory adjustments to extra-uterine life.

Serum Somatomedin Activity after Hypophysectomy and during Parturition in Fetal Lambs*

Somatomedins, detectable by sulfation factor activity (SFA) and/or somatomedin-like receptor activity (SmLRA), were measured in the serum of 72 normal fetal lambs of varying gestational ages and in 12 fetuses before and after hypophysectomy. Three hypophysectomized fetal lambs were infused with GH and/or insulin. Three intact fetal lambs were infused with glucose. Parturition was induced by infusion of synthetic ACTH into 5 fetal lambs. SmLRA and SFA were compared to a pool of adult sheep serum arbitrarily designated 1.00 U/ml. Serum SmLRA correlated significantly with gestational age (r = 0.65; P < 0.001), the linear regression line passing through 0.5 U/ml at 50 days and 2 U/ml at 150 days of gestation. Serum SFA also correlated with gestational age (r = 0.40; n = 19; 0.1 > P > 0.05). Serum SmLRA and SFA were unchanged by hypophysectomy of the fetus and GH infusion but were reduced by insulin infusion. Plasma SmLRA correlated negatively with plasma insulin during glucose infusion (r = -0.67; P < 0.05). During induction of parturition with ACTH, serum SmLRA fell by a mean of 38% and concentrations correlated negatively with plasma cortisol (r = -0.62; P < 0.001). It is concluded that serum somatomedin activity in fetal sheep is not GH dependent. It is possible that somatomedin activity in cord blood after spontaneous delivery may not accurately reflect concentrations prevailing in fetal life.