Search PubMed⌕ Search

Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 73 records · Page 4Linked to original sources
PubMed1996

Influence of sedation on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs.

Our aim was to determine the effects of two commonly used sedatives, promethazine and diazepam, on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs. In eight lambs fitted with obstructable rubber face masks, we recorded electrocortical, electroocular, and electromyographic activities to identify sleep-wake states; intrapleural pressure, heart rate, and percentage O2 saturation (Sao2) were also recorded. In each lamb, arousal and respiratory responses were measured after tidal airflow was obstructed during rapid eye movement (REM) and nonREM sleep. Each lamb was studied, on different days, when unsedated and after being mildly sedated with either promethazine or diazepam. Seven of the lambs were studied while sleeping after being sedated with promethazine (1.6 +/- 0.07 mg/kg, orally with milk) and six were studied after sedation with diazepam (0.31 +/- 0.03 mg/kg, intramuscularly). In unsedated lambs, airflow obstruction led to augmentation of respiratory efforts, bradycardia, hypoxemia, and arousal; in REM sleep, arousal was delayed and occurred at lower Sao2 (16 +/- 3 s; 75.3 +/- 3%) compared with nonREM sleep (8 +/- 1 s; 90 +/- 1%). Sedation increased the arousal latency in both REM and nonREM sleep and caused arousal to occur at lower Sao2; in some sedated lambs Sao2 fell to less than 30% before arousal. The augmentation of inspiratory and expiratory efforts immediately before arousal was increased after sedation. We conclude that promethazine and diazepam depress arousal responses in sleeping lambs leading to profound hypoxia, and that this may be due to impaired sensitivity to augmented respiratory efforts and other physiologic changes during airflow obstruction.

Animals↗
PubMed1996

Children with cancer: the needs of siblings.

Siblings have been identified as the most neglected of all family members during serious childhood illnesses. Siblings of children with cancer can experience great stress. Nurses can support the whole family and encourage positive coping mechanisms among siblings.

Adaptation, Psychological↗
PubMed1996

Origin and evolution of Native American mtDNA variation: a reappraisal.

The timing and number of prehistoric migrations involved in the settlement of the American continent is subject to intense debate. Here, we reanalyze Native American control region mtDNA data and demonstrate that only an appropriate phylogenetic analysis accompanied by an appreciation of demographic factors allows us to discern different migrations and to estimate their ages. Reappraising 574 mtDNA control region sequences from aboriginal Siberians and Native Americans, we confirm in agreement with linguistic, archaeological and climatic evidence that (i) the major wave of migration brought one population, ancestral to the Amerinds, from northeastern Siberia to America 20,000-25,000 years ago and (ii) a rapid expansion of a Beringian source population took place at the end of the Younger Dryas glacial phase approximately 11,300 years ago, ancestral to present Eskimo and Na-Dene populations.

Biological Evolution↗
PubMed1995

Ventilatory responses to progressive hypoxia and hypercapnia in developing sheep.

We aimed to determine the time course of postnatal development of ventilatory responsiveness to progressive hypoxia and hypercapnia. Eight lambs underwent hypoxic and hypercapnic rebreathing tests at weekly intervals from soon after birth to 6 weeks of age. Six mature ewes were also studied. During the tests blood samples were collected at intervals from the aorta so that arterial PO2 (PaO2) and PCO2 (PaCO2) could be related to ventilation. Hypoxic sensitivity was defined as the percentage increase in minute ventilation when PaO2 fell from control values (104.7 +/- 6.9 mmHg) to 50 mmHg. When measured in this way, hypoxic sensitivity increased significantly from 64.2 +/- 19.3% (mean +/- SE) in the newborn (2.3 +/- 0.4 days) to 150.4 +/- 14.0% at 3-4 weeks (25.1 +/- 0.6 days, P = 0.05). The hypoxic sensitivity of ewes (66.3 +/- 16.8%) was greatly reduced compared to 6-week-old lambs (140.3 +/- 18.9%, P < 0.05). Hypercapnic sensitivity (ml.min-1.kg-1.mmHg CO2(-1)) did not change significantly with age. We conclude that hypoxic sensitivity increases during the first 3-4 postnatal weeks and declines between infancy and adulthood. In contrast hypercapnic sensitivity does not change with age, although tidal volume and breathing frequency contributions to ventilatory responses change with advancing postnatal age.

Aging↗
PubMed1995

Sustained alterations in postnatal respiratory function following sub-optimal intrauterine conditions.

This paper reviews recent evidence from epidemiological, follow-up and experimental studies that sub-optimal conditions during gestation can cause alterations in respiratory function that persist during postnatal life. Several studies indicate that placental insufficiency, which can be associated with fetal substrate deprivation, hypoxia and low birthweight, may be followed by evidence of respiratory compromise in later life. Similarly, it is becoming evident that maternal smoking affects fetal lung development and that the effects can persist into postnatal life. A reduced period of fetal development, due to preterm birth, may be associated with prolonged postnatal respiratory consequences which are independent of factors operating during the early postnatal period. Disorders of pregnancy that compress the fetal lungs, or that cause the abolition of fetal breathing movements, commonly lead to lung hypoplasia. We have been interested in the prenatal causes and postnatal effects of fetal lung hypoplasia and have used an ovine model of lung hypoplasia induced by prolonged removal of amniotic fluid. This leads to a reduction in the expansion of the fetal lungs which appears to be a common underlying cause of fetal lung hypoplasia. Studies of lung function in lambs chronically exposed as fetuses to a lack of amniotic fluid showed that, although lung hypoplasia was apparently present throughout the 28-day postnatal study period, major alterations in respiratory function were attributable to changes in chest wall compliance. Thus, it is apparent that sub-optimal intrauterine conditions can have lasting effects on the structure and function of respiratory organs. Available evidence indicates that the degree to which these organs can recover postnatally may be restricted.

Animals↗
PubMed1995

Cerebral blood flow is increased throughout 12 h of hypoxaemia in the mid-gestation ovine fetus.

The changes in regional cerebral blood flow (CBF) in response to prolonged hypoxaemia were measured using coloured microspheres in the 0.6-gestation ovine fetus (n = 5). Fetal hypoxaemia was induced for 12 h by reducing maternal uterine blood flow with an adjustable clamp. CBF (mL min-1 100 g-1) was increased (P < 0.05) from control values (38.7 +/- 3.5) to 105.6 +/- 5.6 at 6 h of hypoxaemia, and to 121.9 +/- 23.1 at 12 h of hypoxaemia. One hour after fetal hypoxaemia had ceased, CBF (54.0 +/- 3.3) had decreased (P < 0.05) towards control values indicating incomplete cardiovascular recovery. Cerebral vascular resistance at 6 h and 12 h of hypoxaemia was lower (P < 0.05) than control values, and returned to control values 1 h after fetal hypoxaemia had ceased. Cerebral oxygen delivery at 6 h and 12 h of hypoxaemia was not significantly different from control values, but was higher (P < 0.05) 1 h after hypoxaemia had ceased. It is concluded that CBF is sufficiently increased during prolonged hypoxaemia in the mid-gestation fetus to maintain cerebral oxygen delivery.

Animals↗
PubMed1995

Restitution of swallowing in the fetal sheep restores intestinal growth after midgestation esophageal obstruction.

We have shown that, in the fetal sheep, abolition of fluid ingestion early in gestation results in a profound gastrointestinal tract (GIT)-specific growth retardation and that these effects can be reversed if fetal swallowing is restored, even for relatively short periods (15 days). The fetal esophagus was ligated at 60-65 days of gestation in 11 fetal sheep (term is 145-148 days). At 136 days of gestation, body and tissue growth of six fetuses were compared to eight age-matched control fetuses. There were no effects on body growth, but the growth of the GIT was significantly retarded. The small intestine was the most severely affected region; villi were smaller in both proximal and distal regions, and villus density was increased and crypt density decreased. The growth-retarding effects are progressive such that they become more pronounced as the period of absence of swallowed input to the GIT is increased. Thus the effects observed in our study (ingestion abolished for approximately 80 days) are much more marked than those in our earlier short-term studies (40-50 days). Five of the fetuses with esophageal ligations underwent further surgery at approximately 120 days' gestation to correct the esophageal obstruction so as to allow the resumption of fluid ingestion. By 136 days, the values of most intestinal morphological parameters had begun to move toward control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1995

Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung.

1. During fetal life the lung develops as a liquid-filled organ. This liquid is produced by the fetal lung and leaves via the trachea from where it is either swallowed or enters the amniotic sac. Fetal lung liquid plays a crucial role in the growth and development of the lungs by maintaining them in a distended state. It is now recognized that the retention of liquid within the future airways is required to maintain the lungs at an appropriate level of expansion in order to stimulate their growth. Indeed, it is likely that most, if not all, of the conditions and malformations that lead to inadequate growth of the fetal lung do so by reducing the volume of lung liquid and hence the degree of lung expansion. 2. The volume of fetal lung liquid is principally regulated by the resistance to lung liquid efflux through the fetal upper airway and by the presence of diaphragmatic activity associated with fetal breathing movements (FBM). During non-breathing periods, the relatively high resistance offered by the upper airway to the efflux of lung liquid opposes the loss of liquid from the lung, thereby maintaining fetal lung expansion. During episodes of FBM, when the larynx is actively dilated and the resistance to lung liquid efflux is reduced, lung liquid leaves the lungs at an increased rate. However, selective inhibition of diaphragmatic muscle activity in the foetus leads to a reduction in lung liquid volume, rather than an increase. This finding indicates that during periods of FBM, rhythmical contractions of the diaphragm retard the loss of lung liquid and help to maintain lung expansion when the upper airway resistance is reduced. It is now apparent that the maintenance of lung expansion by FBM is the basis for their role in promoting fetal lung growth. 3. Successful transition from intra-uterine to extra-uterine life is dependent upon the clearance of liquid from the fetal lungs at the time of birth so that the lungs may effectively function as an organ of gas exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Postnatal development of responses to airflow obstruction.

1. Obstruction of the upper airway could be an initiating factor in the Sudden Infant Death Syndrome (SIDS). Responses to upper airway obstruction include augmentation of respiratory efforts, active dilation of the upper airway and electrocortical arousal. Vulnerable individuals may fail to mount these responses effectively. 2. Respiratory and arousal responses to obstruction of the upper airway have been investigated in newborn lambs. In conscious lambs, nasal obstruction causes a profound augmentation of inspiratory efforts, mild asphyxiation and eventual formation of an oral airway. The ability to establish an oral airway involves both chemoreception and mechanoreception and improves with age. 3. In sleeping lambs, obstruction of tidal airflow leads to progressive hypoxaemia, augmentation of inspiratory efforts, bradycardia and arousal. Arousal occurs earlier and with less hypoxaemia and bradycardia in non-REM sleep than in REM sleep. Arousal occurs after inspiratory efforts have increased to the same extent during both sleep states, suggesting that mechanoreception, or a sense of inspiratory effort, is important in initiating arousal. 4. Obstruction of nasal tubes tends to cause arousal from sleep earlier, and with less hypoxaemia and less augmentation of inspiratory effort, than when a more compliant face mask is obstructed. This supports the suggestion that mechanoreception, which may be involved in the perception of inspiratory effort, is a determinant of arousal. 5. With increasing postnatal age, lambs become less arousable in response to airflow obstruction when in REM sleep. This suggests that lambs may become progressively more vulnerable to the effects of airway obstruction during the immediate newborn period.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1995

Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia.

Our aim was to compare the effects of short (4 h) and prolonged (24 h) periods of reduced uterine blood flow (RUBF) on fetal and placental uptake of O2, glucose, and lactate. In pregnant sheep, uterine and umbilical blood flows were measured under normal conditions and after 4 and 24 h of RUBF. A 50% reduction in uterine blood flow caused a 56% reduction in fetal arterial O2 saturation (SaO2). Umbilical blood flow increased from 325 +/- 33 to 378 +/- 32 ml.min-1.kg-1 (P < 0.05) after 4 h but was not different from pre-RUBF values after 24 h. O2 uptake by the gravid uterus was not altered by RUBF, due to an increase (84%) in uterine O2 extraction. Similarly, uteroplacental and fetal O2 consumptions and fetal glucose uptake were not affected by RUBF, whereas uteroplacental glucose uptake was significantly reduced after 4 h (by 42%) and 24 h (by 58%) of RUBF. Fetal lactate uptake was greatly reduced from 78.7 +/- 15.5 to -167 +/- 57 mumol.min-1.kg-1 after 4 h and to -198 +/- 80 mumol.min-1.kg-1 after 24 h of RUBF; negative values indicate placental lactate uptake from the fetal circulation. Thus, although RUBF significantly reduced fetal SaO2, fetal and uteroplacental O2 consumptions did not change. In addition, although fetal glucose uptake was not altered by RUBF, during RUBF the placenta became a major site of lactate clearance from the fetal circulation.

Animals↗
PubMed1995

Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid.

We have examined the role of cortisol in the gestational age-related increase in the ability of epinephrine to inhibit the secretion and induce the reabsorption of fetal lung liquid. Chronically catheterized fetal sheep were infused with either saline (n = 6) or increasing doses of cortisol (1.5-3.5 mg/day; n = 6) between 120 and 130 days of gestation (term approximately 145 days). Lung liquid volumes and secretion rates were measured at 120 days (before infusion) and at 125 days, and then at 130 days we tested the ability of epinephrine to inhibit lung liquid secretion and induce liquid reabsorption. Cortisol infusions increased fetal plasma cortisol and 3,5,3'-triiodothyronine (T3) concentrations to levels observed just before labor and significantly increased the age-related increase in fetal lung liquid volume and secretion rate. At 130 days, epinephrine caused a significantly greater rate of lung liquid reabsorption in cortisol-infused fetuses (10.3 +/- 2.3 ml/h) than in saline-infused fetuses (1.5 +/- 1.6 ml/h). We conclude that a premature elevation in circulating fetal cortisol concentrations, probably in conjunction with elevated T3 concentrations, prematurely increases the epinephrine-induced reabsorption of fetal lung liquid. It is likely, therefore, that the preparturient increase of fetal cortisol concentrations plays an important role in the clearance of lung liquid at birth.

Absorption↗
PubMed1995

Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production.

Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure.

Acids↗
PubMed1995

Lung hypoplasia can be reversed by short-term obstruction of the trachea in fetal sheep.

Our aim was to determine whether an existing lung growth deficit could be reversed, in utero, by short-term (6 d) obstruction of the fetal trachea. Chronically catheterized fetal sheep (term approximately 145 d) were divided into four groups: 1) no treatment (control); 2) continuous lung liquid drainage to induce lung hypoplasia (105-134 d, drain); 3) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by restoration of tracheal flow (128-134 d, drain and reconnect); and 4) lung liquid drainage to induce lung hypoplasia (105-128 d), followed by tracheal occlusion to accelerate lung growth (128-134 d, drain and obstruct). Lung liquid volumes and secretion rates were measured on d 125, 130, and 134 of gestation and postmortem data collected on d 135. Compared with controls, continuous lung liquid drainage (drain) significantly reduced wet lung weights (34.3 +/- 2.6 g/kg versus 13.3 +/- 1.4 g/kg) and total lung DNA contents (177 +/- 11 mg/kg versus 94 +/- 7 mg/kg). Reestablishing tracheal flow for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 +/- 1.6 g/kg), but not total DNA contents (106 +/- 9 mg/kg), compared with lung liquid drained fetuses (drain). After 6 d of tracheal obstruction (drain and obstruct) lung liquid volumes, wet lung weights, and total protein contents (weight, 28.6 +/- 2.8 g/kg; protein, 1376 +/- 97 mg/kg) were similar to control values (weight, 34.3 +/- 2.6 g/kg; protein, 1506 +/- 123 mg/kg); lung DNA contents were less than control but greater than values from lung liquid drained fetuses (drain and obstruct, 140 +/- 9 mg/kg versus drain, 94 +/- 7 mg/kg). We conclude that obstruction of the trachea can reverse an existing fetal lung growth deficit in approximately 6 d, whereas merely restoring tracheal continuity does not increase fetal lung growth.

Airway Obstruction↗