Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 19 recordsLinked to original sources

PubMed1992

Ultrastructural anomalies in the fetal small intestine indicate that fetal swallowing is important for normal development: an experimental study.

Fetal swallowing is established early in development and if fetal ingestion is prevented, the gastrointestinal (GI) tract fails to grow normally. In this article we describe the ultrastructural features of GI tissues developing in the absence of swallowing, in the fetal sheep. We have noted a number of defects in enterocyte morphology. These include abnormal or absence of microvilli, inappropriate cell extrusion, glycogen accumulation and altered lysosomal morphology. Many of these changes resemble those seen in malnourished infants. It is possible that fetal ingestion provides a significant source of nutrients, ensuring adequate GI tract growth in utero, in addition to specific growth factors which may be present in ingested fluid.

Amniotic Fluid↗

PubMed1992

Role of prostaglandins in the metabolic responses of the fetus to hypoxia.

OBJECTIVE: The effect of inhibiting prostaglandin synthesis on the fetal metabolic response to hypoxemia was examined by infusing indomethacin during periods of reduced maternal uterine blood flow. STUDY DESIGN: In seven fetal sheep we administered a 6-hour infusion of either indomethacin (n = 5), indomethacin plus prostaglandin E2, or a vehicle solution (n = 5). The last 4 hours of each infusion period coincided with a period of fetal hypoxemia induced by reduced maternal uterine blood flow. RESULTS: During reduced maternal uterine blood flow indomethacin infusions caused a significantly greater reduction in pHA (reduced from 7.36 +/- 0.01 to 7.10 +/- 0.02) than both the vehicle (from 7.36 +/- 0.01 to 7.20 +/- 0.03) and indomethacin plus prostaglandin E2 infusions (from 7.36 +/- 0.01 to 7.18 +/- 0.02). Before reduced maternal uterine blood flow was induced, indomethacin significantly elevated fetal plasma glucose and lactate concentrations from 0.6 +/- 0.04 and 2.2 +/- 0.1 to 1.3 +/- 0.2 and 6.7 +/- 0.7 mmol/L, respectively. During reduced maternal uterine blood flow indomethacin caused a significantly greater increase in plasma glucose and lactate concentrations than the vehicle; plasma glucose and lactate concentrations increased to a maximum of 1.8 +/- 0.2 and 22.7 +/- 0.8 mmol/L, respectively, during indomethacin infusions compared with 1.1 +/- 0.1 and 15.7 +/- 1.7 mmol/L, respectively, during vehicle infusions. The addition of prostaglandin E2 to the indomethacin infusion prevented the enhanced increase in glucose and lactate concentrations during reduced maternal uterine blood flow and caused a significant increase in fetal plasma insulin concentrations from 12.6 +/- 0.7 to 60.9 +/- 28.1 microU/ml. CONCLUSION: The inhibition of prostaglandin synthesis during fetal hypoxemia alters the metabolic response of the fetus, leading to a severe metabolic acidosis.

Animals↗

PubMed1992

The effects of glycemia on breathing movements and plasma prostaglandin E concentrations in the sheep fetus.

OBJECTIVE: The purpose of this study was to determine the roles of fetal plasma glucose and prostaglandin E in controlling fetal breathing movements. STUDY DESIGN: Five late pregnant ewes with catheterized twin fetuses were fasted for 48 hours; one fetus was kept normoglycemic (by glucose infusion) and the other allowed to become hypoglycemic during this period. Fetal breathing movement and fetal and maternal plasma prostaglandin E and glucose concentrations were measured throughout. Data were analyzed by paired and unpaired t tests. RESULTS: The mean incidence of fetal breathing movement was significantly greater in the normoglycemic fetuses that in the hypoglycemic twins at the end of the fast (p less than 0.05), whereas plasma prostaglandin E levels increased significantly (p less than 0.05) and to the same extent in both groups of fetuses. CONCLUSION: The reduced incidence of ovine fetal breathing movement that occurs during maternal fasting appears to be primarily caused by fetal hypoglycemia and does not directly involve changes in fetal plasma prostaglandin E.

Animals↗

PubMed1992

Fetal-maternal fluid and electrolyte relations during chronic fetal urine loss in sheep.

Our aim was to determine the effects of prolonged removal of fetal urine during late gestation on fetal-maternal fluid and electrolyte relationships. We measured the volume and composition of fetal urine and amniotic and allantoic fluids and the composition of fetal and maternal plasma in sheep before and during continuous urine drainage, which began at 130 days of gestation and continued until the onset of labor; a control group was also studied. The response to fetal urine drainage occurred in two phases. In the "acute" phase (1-3 days), amniotic and allantoic fluid volumes decreased significantly, presumably due to their reabsorption into the fetal chorionic circulation or swallowing of amniotic fluid by the fetus. During the "chronic" phase, starting 3-5 days after urine drainage, a significant reversal in the transplacental osmotic gradient occurred due to a decrease in maternal plasma osmolality. During the entire drainage period (14.1 +/- 1.1 days, mean +/- SE, n = 5) at least 542 ml/day of water and 24 mmol/day of electrolytes passed from the mother into the fetal circulation and fetal plasma osmolality was unchanged. We conclude that, despite the loss of substantial water and electrolytes, the fetus is able to maintain its growth and fluid and electrolyte homeostasis by obtaining water and electrolytes initially from the amniotic and allantoic fluids and subsequently from its mother. The movement of water and electrolytes to the fetus would have been facilitated by the reversed transplacental osmotic gradient.

Animals↗

PubMed1992

The influence of gestational age and onset of labour on determinants of fetal-maternal fluid and electrolyte balance in sheep.

Our aim was to compare the effects of gestational age and the timing of the onset of labour on factors influencing fetal fluid and electrolyte balance and urine production in fetal sheep. We measured the volume and composition of fetal urine and amniotic and allantoic fluids, as well as fetal and maternal plasma composition and micturition episodes in sheep during late gestation until the onset of labour. We found that daily fetal urine production and urethral urine flow per micturition episode increased significantly in relation to the onset of labour but not to gestational age (P < 0.05). In the 2 days preceding the onset of labour fetal urine and amniotic fluid K+ concentrations and urine osmolality increased significantly and the Na+/K+ ratio in allantoic fluid decreased significantly (P < 0.05). There was also a significant fall in fetal arterial SaO2 (P < 0.05) but no significant changes occurred in fetal plasma electrolyte composition, osmolality or AVP concentrations. Fetal plasma cortisol and prolactin concentrations and amniotic and allantoic fluid prolactin concentrations increased significantly and progressively in association with both advancing gestation and the onset of labour whereas maternal plasma prolactin concentrations increased significantly only in the 2 days before the onset of labour (P < 0.05). We conclude that some developmental aspects of fetal fluid and electrolyte balance, including renal function, are more closely related to the timing of parturition than to gestational age per se.

Amniotic Fluid↗

PubMed1992

G-induced loss of consciousness accidents: USAF experience 1982-1990.

Discussion of acceleration protection measures should be based on analysis of relevant accident data, including determination of high risk aircraft, G profiles, and pilot descriptions. There were 18 accidents (14 fatalities) attributed to G-induced loss of consciousness (G-LOC) in the United States Air Force (USAF) from 1982 through 1990. All 18 accidents occurred during single crewmember sorties, for an average rate of 2.1 per million single-seat flying hours (pmfh). The average G-LOC accident rate for 1982-4 was 4.0 pmfh, decreasing significantly to 1.3 pmfh for 1985-90. This decrease is associated with the USAF initiation of an anti-G-LOC training program. We reviewed accident records for G-LOC cofactor data and compared them to normal data for USAF pilots for age, height, weight, systolic and diastolic blood pressures, heart rate, total flying time, and aircraft-specific flying hours. Only for systolic blood pressure (higher) and aircraft-specific flying hours (shorter) were the mishap pilots significantly different from other USAF pilots. We found no evidence to support weight training vs. aerobic training, missed meals, or heat in causing G-LOC accidents. Thus the mishap pilots appeared to be a representative cross section of USAF pilots with respect to personal variables. More significant factors appeared to be G duration, G magnitude, use of G trousers, and experience in assigned aircraft.

Accidents, Aviation↗

PubMed1991

Growth retardation and the development of the respiratory system in fetal sheep.

In an experimental model of fetal growth retardation which involves the reduction of placental mass in ewes, we have investigated the effects of intrauterine deprivation on aspects of structural development of the trachea and lungs of fetal sheep (140 days gestation). We have also measured the volume of luminal liquid aspirated from the lungs and the phospholipid content of this liquid as an index of pulmonary surfactant production. The effects of growth retardation are evident in the trachea where the structural development of the mucosal and submucosal layers has been affected. Abnormal aspects of development include the frequent lack of a ciliated border on epithelial cells in the mucosal layer and the reduction in the extent of the folds usually characteristic of this layer in near term fetal sheep. Although the fetal lungs are smaller in growth retardation (P less than 0.01) they are appropriate for fetal weight and their structural development does not appear to have been retarded. In contrast, lung liquid volume is significantly reduced in relation to lung weight in growth retarded fetuses and the concentration of phospholipids in lung liquids is also reduced (P less than 0.01).

Animals↗

PubMed1991

The development of the gastrointestinal system in fetal sheep in the absence of ingested fluid.

Our aim was to determine the effects of preventing the passage of ingested fluid on the development of the digestive tract in fetal sheep. The esophagus was fistulated and ligated in six fetuses at 90 days of gestation (term = 145 days); vascular catheters were implanted at day 120. Six control fetuses had vascular catheters implanted at day 120. At autopsy (day 135), although fetal body weights were similar in both groups, the abdominal girth and weights of the gastrointestinal tract, liver, and pancreas were reduced in experimental fetuses. In the gastric (abomasal) fundus and antrum, there was evidence of altered mucus composition in epithelial cells, a decrease in thickness of the muscularis externa, and an increase in thickness of the mucosa and its components. In the duodenum, there were significant changes in the thickness of most components of the wall; Brunner's glands were greatly reduced in size of were absent. Glandular cells contained less mucus in comparison to controls. In the proximal small intestine, there were significant reductions in the thickness of most components of the wall, and epithelial cell migration was retarded, resulting in a longer renewal time for villous cells. In the distal small intestine, the diameter of the intestine and submucosal and epithelial cell migration rate were significantly decreased in the experimental group. In summary, the absence of the passage of ingested fluid in fetal sheep restricts the growth and development of the gastrointestinal tract, liver, and pancreas.

Amniotic Fluid↗

PubMed1991

Fetal breathing and pressures in the trachea and amniotic sac during oligohydramnios in sheep.

Oligohydramnios commonly leads to fetal lung hypoplasia, but the mechanisms are not fully understood. Our aim was to determine, in fetal sheep, the effects of prolonged oligohydramnios on the incidence and amplitude of tracheal pressure fluctuations associated with fetal breathing movements (FBM), on tracheal flow rate during periods of FBM (VtrFBM) and periods of apnea (Vtrapnea), on tracheal pressure relative to amniotic sac pressure, and on amniotic sac pressure relative to atmospheric pressure. In five sheep, oligohydramnios was induced by draining amniotic and allantoic fluids from 107 to 135 days of gestation (411.8 +/- 24.4 ml/day), resulting in fetal lung hypoplasia. In five control sheep, amniotic fluid volume was 732.3 +/- 94.4 ml. Oligohydramnios increased the incidence of FBM by 14% at 120 and 125 days and the amplitude of FBM by 30-34% at 120-130 days compared with controls. From 120 days onward, VtrFBM was 35-55% lower in experimental fetuses than in controls. Influx of lung liquid during FBM was 87% lower in experimental fetuses than in controls. Vtrapnea, tracheal pressure, and amniotic sac pressure were not significantly altered by oligohydramnios. Our tracheal flow rate data suggest that transient changes in lung liquid volume during periods of FBM and periods of apnea were diminished by oligohydramnios. We conclude that the primary factor in the etiology of oligohydramnios-induced lung hypoplasia is not an inhibition of FBM (as measured by tracheal pressure fluctuations) or a reduction in amniotic fluid pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗

PubMed1991

Initiation of oral breathing in lambs in response to airway obstruction: mechanisms.

Our aim was to assess the mechanisms determining the reflex formation of an oral airway in response to nasal obstruction (NO) and tracheal obstruction (TO). In nine conscious lambs (14-37 days old) NO was effected by blockade of nasal tubes; TO was later effected by blockade of an endotracheal tube. We measured arterial O2 saturation, PO2, PCO2, and pH and the depth and duration of inspiratory efforts when mouth opening (MO) occurred. Responses were compared when NO and TO followed breathing of room air, rebreathed air, and 100% O2. After both NO and TO, MO was initiated most rapidly after lambs rebreathed air and least rapidly after they breathed 100% O2. Similar changes in blood gases and pH were measured when MO occurred after air breathing and rebreathing; however, the extent of these changes was greater during TO than during NO. After 100% O2 was breathed, MO occurred when lambs were still hyperoxic, but they were more hypercapnic and acidemic than after breathing air or rebreathed air. There were no differences, related to prebreathed gases or site of airway occlusion, in the depth of inspiratory efforts at the time of MO. We conclude that the formation of an oral airway requires a critical level of inspiratory drive in the presence of airway obstruction. After the prebreathing of different gases, differences in response latency and blood gases at the time of MO can be attributed to the attainment of this threshold level of inspiratory drive. The formation of an oral airway is facilitated by, but not dependent on, receptors in the upper airway.

Airway Obstruction↗

PubMed1991

Respiratory and non-respiratory thoracic movements in the fetal pig.

The aim of this study was to characterize the pre-natal activity of the respiratory muscles in a non-ruminant, the pig. Tracheal pressure was recorded from 11 unanaesthetized fetal pigs in utero during late gestation in 9 sows. Two types of inspiratory effort occurred episodically in each fetus during each recording period. Episodes of breathing movements lasted 8.6 +/- 1.1 min and their overall incidence was 41.1 +/- 3.4% of recording time. The mean amplitude of the respiratory efforts was 7.6 +/- 1.1 mmHg and the mean inspiratory time was 0.8 +/- 0.1 s. Episodes of non-respiratory inspiratory efforts, considered to be fetal hiccups, lasted 5.6 +/- 0.8 min. Individual hiccups had a duration of 150-200 msec, a mean amplitude of 41.4 +/- 2.4 mmHg and a mean frequency, during episodes, of 21.9 +/- 2.0 min-1. In contrast to fetal breathing movements, hiccups appeared to be stereotyped events. It is concluded that, in common with other ruminant and non-ruminant species, two types of inspiratory effort occur in the fetal pig. Fetal hiccups, which have been observed in non-ruminant species, may be analogous to deep inspiratory efforts in the sheep fetus. The stimulus for, and function of, fetal hiccupping remain to be determined.

Animals↗

PubMed1991

Compliances of the liquid-filled lungs and chest wall during development in fetal sheep.

Our aim was to measure the compliance of the liquid-filled lungs (CL), and the compliance of the chest wall (CW) in fetal sheep in utero. CL and CW were measured in 6 fetuses. The compliance of the lungs and chest wall combined (respiratory system, Crs) was measured in 9 fetuses. Pressure differences across the lungs (PL), chest wall (PW) and respiratory system (Prs) were measured while the lungs were deflated and inflated with liquid from their resting lung liquid volume (V1). V1 was measured using an indicator dilution technique. Specific compliance values were obtained by normalizing the values of CL, CW and Crs with respect to values of V1. From values obtained during stepwise inflation from V1, specific compliances (ml/cm H2O/ml of lung liquid) were: lungs, 0.22 +/- 0.02; chest wall, 0.41 +/- 0.07; respiratory system, 0.13 +/- 0.01. Specific compliances of the lungs, chest wall and respiratory system did not change significantly with advancing gestational age from 120 to 143 days. Our baseline data will be valuable in assessing the in utero progress of the structural development of the lungs following manipulations known to cause altered lung growth.

Animals↗

PubMed1991

The influence of oligohydramnios on thoracic dimensions of fetal sheep.

Oligohydramnios frequently leads to lung hypoplasia in the fetus, but the underlying mechanisms are incompletely understood. Our aim was to determine the effects of oligohydramnios on the dimensions of the fetal thorax. Using pairs of implanted ultrasound transducers in 6 fetal sheep, we measured 4 thoracic dimensions (transverse, anterior-posterior, manubrium to left and right hand sides of the diaphragmatic dome) for 2 control days, 3 days of amniotic and allantoic fluid drainage (oligohydramnios), and 2 days after the return of drained fluids. The effect of oligohydramnios, which began at 121-2 days of gestation (term being c.145 days), on each dimension was quantified daily as the difference between the measured value and the value predicted from the growth of that dimension over the study period. Oligohydramnios led, within 48 hours, to significant reductions in the transverse dimension (5.9-6.1%) and in the distance between the manubrium and the dome of the diaphragm (1.7-2.2%). There was no change in the anterior-posterior dimension. We conclude that oligohydramnios causes alterations, within 48 hours, in the dimensions of the fetal thorax which can be reversed, at least partially, by re-expansion of the fluid sacs. These changes, which are expected to produce reductions in thoracic volume, may, if prolonged, lead to lung hypoplasia.

Animals↗

PubMed1990

A mechanism leading to reduced lung expansion and lung hypoplasia in fetal sheep during oligohydramnios.

Our aim was to determine the mechanism whereby oligohydroamnios causes reduced fetal lung expansion and eventual lung hypoplasia. We studied 20 fetal sheep during 2 to 9 days of oligohydramnios produced by drainage of amniotic and allantoic fluids during the last third of gestation. Oligohydramnios led to a reversible reduction in lung liquid volume of 19.5% within 48 hours. During oligohydramnios tracheal pressure, relative to amniotic pressure, rose by 1.7 mm Hg (p less than 0.001); pressures also tended to rise in the fetal pleural space and abdomen, relative to amniotic pressure, and to fall in the amniotic sac. Pressure increments, relative to amniotic pressure, which normally occur in the fetal trachea, pleural cavity, and abdomen during nonlabor uterine contractions, were significantly increased by 1.9 to 2.5 mm Hg during oligohydramnios. Oligohydramnios increased flexion of the fetal thoracolumbar spine, quantified as a reduction in the ratio of spinal radius of curvature to spine length (0.76 in controls vs 0.40 after oligohydramnios, p less than 0.001). In three sets of twins, only the fetus exposed to oligohydramnios was affected. A similar degree of spinal flexion imposed on normal fetal sheep cadavers increased abdominal (1.6 mm Hg), pleural (1.5 mm Hg), and tracheal (2.0 mm Hg) pressure, and caused a significant reduction in fetal lung expansion. We conclude that oligohydramnios in fetal sheep increases spinal flexion, leading to compression of abdominal contents, upward displacement of the diaphragm, and lung compression, favoring loss of fetal lung liquid. These changes, which are accentuated during nonlabor uterine contractions and are reversible, may lead to pulmonary hypoplasia if prolonged.

Abdomen↗

PubMed1990

The role of carotid bodies in the establishment of oral breathing during nasal obstruction in lambs and ewes.

This study was aimed at determining the role of carotid bodies in the initiation and maintenance of oral breathing during nasal obstruction. We have previously shown in sheep that oral breathing during nasal obstruction was less effective in the neonate than in older lambs or adults. We considered it possible that the reduced response of the neonate was due to immaturity of carotid body chemoreceptors. Respiratory and blood gas responses to nasal obstruction were determined in 5 neonatal lambs, 6 older lambs and 6 adult ewes before and after surgically denervating the carotid bodies. Denervations were performed at 4.2 +/- 0.9 days after birth in the neonatal lambs and at 41.5 +/- 2.5 days in the older lambs. Carotid body denervation led to hypoxia, hypercapnia and acidaemia in lambs and ewes during unobstructed nasal breathing, and, in response to nasal obstruction, delayed the onset of oral breathing so that it occurred at a greater degree of hypoxia. Following carotid body denervation the degree of hypercapnia and acidaemia during nasal obstruction was greater in lambs than in ewes. We conclude that the carotid bodies in lambs and ewes play an important role in the regulation of normal blood gases and pH, and in the establishment and effectiveness of oral breathing during nasal obstruction.

Animals↗

PubMed1990

The effects of intrauterine growth retardation on the structural development of cranial nerves (optic, trochlear) in fetal sheep.

A quantitative morphometric study of the development of myelinated fibres in the optic and trochlear nerves has been made in growth-retarded fetal sheep at 140 days gestation (term = 146 days). Intrauterine growth retardation was induced as a result of the reduction of placental mass, by prior removal of placentation sites in six ewes. In the optic nerve (central nervous system) the mean diameter of myelinated fibres was not significantly reduced but the thickness of the myelin sheath relative to axon diameter was disproportionately reduced. In the trochlear nerve (peripheral nervous system) there was a significant reduction of 23% (P less than 0.01) in the mean diameter of myelinated fibres; however the normal axon:myelin ratio was maintained. The total number of myelinated fibres in the trochlear nerve did not differ between the normal and growth-retarded group, indicating that there was not a greater than normal incidence of cell death during intrauterine growth retardation in the nucleus of the trochlear nerve. The differential effect of intrauterine growth retardation on myelination in the central and peripheral nervous systems suggests that chronic intrauterine deprivation affects oligodendrocyte activity but does not markedly affect the capacity of Schwann cells to produce myelin.

Animals↗

PubMed1990

Regulation of lung liquid secretion by arginine vasopressin in fetal sheep.

We have investigated the influence of gestational age on the inhibition of fetal lung liquid secretion by arginine vasopressin (AVP). In eight fetal sheep, lung liquid secretion rates were measured before and during infusion of AVP (300 mu.kg-1.h-1) at gestational ages between 110 and 148 days. During infusions, the concentration of AVP in fetal plasma increased from less than 8.7 +/- 0.2 pg/ml to 848.7 +/- 75.1 pg/ml. Fetal plasma epinephrine concentrations were not altered during AVP infusion. Infusions of AVP had no effect on fetal lung secretion before 135 days of gestation; they caused a 40.8% inhibition between 136 and 140 days, and at ages greater than 140 days induced an inhibition of 78.4%. In two ewes during labor, AVP infusion caused either a complete inhibition of secretion or reabsorption of lung liquid. The inhibitory effect of AVP increased in an exponential-like fashion with increasing gestational age and appeared to parallel the preparturient rise in fetal plasma cortisol concentrations. Our results indicate that AVP may be involved in the clearance of lung liquid at term and that AVP is unlikely to mediate the inhibitory effect of fetal asphyxia on lung liquid secretion, at least until after 135 days of gestation.

Animals↗

PubMed1990

Fetal endocrine responses to prolonged hypoxemia in sheep.

Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E2 (PGE2) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 +/- 3.6 to 20.3 +/- 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 +/- 4.5 min/h and 7.36 +/- 0.01 to 4.3 +/- 1.8 min/h and 7.13 +/- 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 +/- 0.5 pg/ml and 0.19 +/- 0.05 ng/ml to 333.8 +/- 41.5 pg/ml and 1.5 +/- 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 +/- 0.4 and 4.0 +/- 2.2 ng/ml to 6.1 +/- 1.8 and 13.5 +/- 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE2 concentrations progressively increased (from 1.9 +/- 0.4 to 8.8 +/- 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE2 during RUBF was very similar to the increases in arterial pH and in the incidence of FBM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗