PubMed Health⌕ Search

Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 55 records · Page 3Linked to original sources
PubMed1987

Role of upper airway in ventilatory control in awake and sleeping dogs.

We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.

Animals↗
PubMed1986

Conduction velocity in peripheral nerve of foetal, newborn and adult sheep.

Measurements have been made of conduction velocity in tibial and peroneal divisions of the sciatic nerve in foetal, newborn and adult sheep. Foetal age ranged from 91 days after mating to term, at 145 days. Measurements on foetuses used chronically implanted electrodes in 6 animals and direct nerve recordings in two acute preparations. For chronic recordings, two pairs of stimulating electrodes were placed as far apart along the nerve as possible and recording electrodes measured the electromyogram of the lateral gastrocnemius muscle. In the nerve recordings stimulating electrodes were placed at several different sites and the latency of the nerve action potential at each site was plotted against electrode separation. Values of maximum conduction velocity in foetal tibial nerve ranged from 24 m/s at 91 days to 60 m/s at term. Conduction velocity increased by 0.6 m/s per day. In the newborn lamb conduction velocity was more than half of the adult value of 96 m/s, indicating the relative maturity of the sheep at birth compared with other mammals.

Animals↗
PubMed1986

Effects of reduced uterine blood flow on electrocortical activity, breathing, and skeletal muscle activity in fetal sheep.

Experiments were conducted in 11 unanesthetized fetal sheep during the last third of gestation to examine the effects of prolonged, reversible reduction in uterine blood flow on fetal electrocortical activity, breathing movements, and skeletal muscle activity. With an adjustable clamp placed around the maternal common internal iliac artery, uterine blood flow was restricted for 2 hours to produce a reduction in fetal arterial oxygen saturation from 56.1% +/- 1.9% to 28.8% +/- 0.7%. When blood flow was reduced, there was a decrease in the percentage of time that fetuses spent in low-voltage electrocortical activity, from 57.5% +/- 3.0% to 37.8% +/- 3.5%, and a decrease in the incidence of both breathing movements and integrated skeletal muscle activity. Younger fetuses (110 to 121 days' gestation) demonstrated a lesser degree of reduction in breathing movements when compared with older fetuses (125 to 140 days) whereas the effects of hypoxemia on electrocortical activity became less apparent with advancing gestational age.

Animals↗
PubMed1986

Effects of reduced uterine blood flow on accelerations and decelerations in heart rate of fetal sheep.

Experiments were conducted in unanesthetized fetal sheep during the last third of gestation to examine the effects of prolonged reversible reductions in uterine blood flow on mean fetal heart rate, accelerations and decelerations in fetal heart rate, and fetal arterial pressure. With use of a Teflon vascular clamp placed around the maternal common internal iliac artery, uterine blood flow was reduced, leading to a reduction in fetal arterial oxygen saturation from 60% to 30% for 2 hours. This was associated with an initial transient fetal bradycardia and hypertension followed by tachycardia. Mean fetal heart rate remained significantly elevated for 2 hours following the release of the vascular clamp. There was no change in the number, amplitude, or duration of accelerations, but there was a significant increase in both the number and amplitude of decelerations during the period of reduced uterine blood flow.

Animals↗
PubMed1986

Respiratory activity of laryngeal muscles in awake and sleeping dogs.

Experiments were conducted in adult dogs to determine the respiratory activity of laryngeal muscles during wakefulness and sleep. We studied the EMG activity of three laryngeal muscles in five trained dogs, two of which were completely intact, and three of which had a previously-formed side-hole tracheal stoma. Pairs of electrodes were implanted chronically into the posterior cricoarytenoid muscle (PCA), a laryngeal dilator, cricothyroid (CT), and thyroarytenoid (TA), a laryngeal adductor. EMG electrodes were also inserted into the costal portion of the diaphragm. In wakefulness (W), slow wave sleep (SWS) and rapid eye movement (REM) sleep the EMGs of the PCA and CT muscles increased in intensity during diaphragm activation, with varying levels of basal activity during expiration. However, the greatest levels of inspiratory activity in PCA and CT during sleep were found in REM sleep, usually in the absence of augmented diaphragm EMG activity. This laryngeal muscle activity was associated with laryngeal dilation. There were also marked state-related changes in the level of activity of CT during expiration, suggestive of changes in the degree of expiratory adduction of the larynx. The adductor muscles (TA) were not active during expiration, except during alert W. There were no consistent differences in respiratory activity of the laryngeal muscles between the two intact dogs and those with a tracheal stoma (whether or not an endotracheal tube was in place), nor was laryngeal muscle activity affected by the subsequent creation of a tracheal stoma in the two intact dogs. The findings indicate that sleep-wakefulness state exerts important influences on the respiratory activity of laryngeal muscles in the adult dog.

Airway Resistance↗
PubMed1986

Laryngeal muscle activities during progressive hypercapnia and hypoxia in awake and sleeping dogs.

Laryngeal, intercostal and diaphragmatic muscle activities were recorded during progressive hypercapnia and hypoxia in dogs with chronically implanted electrodes. As ventilation increased during progressive chemoreceptor stimulation, inspiratory activity of the posterior cricoarytenoid muscle, a laryngeal abductor, and of the cricothyroid muscle were augmented. When expiratory flow rates reached 2-3 times resting levels, both of these muscles were also active during expiration and recruitment of the internal intercostal muscles was observed. The thyroarytenoid muscle, a laryngeal adductor, was active only rarely and no consistent activation of this muscle was observed with either hypercapnia or hypoxia. The patterns of muscle activation in response to respiratory stimulation were not different during wakefulness, slow wave sleep, and rapid eye movement sleep. The results indicate that the laryngeal muscles are activated during hypercapnia and hypoxia in a manner which reduces both inspiratory and expiratory airflow resistance regardless of sleep-wakefulness state.

Animals↗
PubMed1986

The role of ingestion in the development of the small intestine in fetal sheep.

We have examined the influence of preventing the passage of swallowed fluid on the development of the small intestine during late gestation in fetal sheep. In four fetuses at 90 d of gestation, the oesophagus was ligated and fistulated, causing swallowed fluid to enter the amniotic sac. Tissue was removed from proximal and distal parts of the small intestine for histological analysis at 136 d (term is 147 d). The body weights of the four experimental fetuses were not significantly different from those of fourteen age- and breed-matched fetuses which were used as controls. However, the width of the mucosal layers at both sites in the small intestine was reduced by approximately 25% in the fistulated fetuses. This was largely attributable to a reduction in villus height of approximately 30%. The densities of villi and crypts increased significantly at the proximal and distal sites respectively. These findings indicate that the ingestion of fluid during late gestation plays a role in promoting growth of the mucosal elements of the small intestine. The way in which this occurs is not clear although it may be mediated either by trophic factors present in either amniotic or pulmonary fluid, or by the release of gastrointestinal hormones, such as gastrin, as a result of gut distension.

Animals↗
PubMed1986

Metabolic response of skeletal muscle to ischemia.

To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.

Adenosine Triphosphate↗
PubMed1986

Upper airway resistances in fetal sheep: the influence of breathing activity.

Fetal breathing movements (FBM) and lung liquid volume are known to affect lung development, but little is known about mechanisms controlling movement of liquid through the upper respiratory tract (URT). Therefore we measured resistances of the URT in 8 unanesthetized fetal sheep during late gestation while FBM were monitored from pressures in the lower trachea or from electromyogram of respiratory muscles. URT resistance to liquid flow toward the amniotic sac increased from 3.5 +/- 1.9 Torr X ml-1 X min during episodes of FBM to 21.1 +/- 5.7 Torr X ml-1 X min during apnea. Laryngeal resistance during apnea was greater (P less than 0.001) than supralaryngeal resistance in each of six fetuses in which URT resistance was partitioned. Fetal paralysis abolished the increase in laryngeal resistance to efflux that was previously related to the high-voltage electrocortical state and apnea. We were unable to quantify URT resistance to fluid movement toward the lungs because the larynx acted as a valve, permitting flow toward the lungs only in the presence of FBM. The supralaryngeal portion of the URT also apparently acts as a valve, normally preventing the entry of amniotic fluid into the pharynx. These findings help to explain our earlier observations that efflux of liquid from the fetal lungs is greater during episodes of FBM than during apnea.

Airway Obstruction↗
PubMed1986

Influence of upper respiratory tract on liquid flow to and from fetal lungs.

The experiments were designed to determine the influence of the upper respiratory tract (URT) on liquid flow in the fetal trachea. This flow probably influences pulmonary distension, which is thought to be a major determinant of prenatal lung development. In six fetal sheep the URT could be bypassed by connecting the lower trachea, via an external flowmeter, to a cannula in the amniotic sac. In confirmation of our earlier findings, when the URT was in circuit, the mean rate of tracheal efflux was greater during episodes of fetal breathing movements (FBM) [mean 13.8 +/- 2.6 (SE) ml/h] than during apneic periods (mean 3.2 +/- 1.0 ml/h). When the URT was bypassed there was a reversal of net tracheal flow during FBM episodes (mean 19.6 +/- 5.6 ml/h toward the lungs); during apnea there was a much greater rate of efflux (mean 33.1 +/- 10.2 ml/h) than when the URT was in circuit. Nonlabor uterine contractions were associated with an increased rate of efflux during apnea only when the URT was bypassed. We conclude that during fetal life the URT imposes an essentially unidirectional flow of pulmonary liquid away from the lungs, preventing ingress of amniotic fluid and maintaining constancy of composition of liquid in the developing airways. By retarding outward flow during periods of apnea and thoracic compression and by preventing net influx during episodes of FBM, the URT has the probable effect of maintaining the volume and composition of liquid in the fetal airways within narrow limits.

Animals↗
PubMed1986

Changes in the innervation and catecholamine concentrations in the myometrium of pregnant and non-pregnant sheep.

The innervation of the myometrium in virgin, pregnant and post-partum ewes was examined using the SPG histofluorescence method and a high-performance liquid chromatographic catecholamine assay. In non-pregnant ewes, fluorescent axons were visible in all regions of the uterus. At 50 days of pregnancy the innervation was unchanged, but at 100 days axons were scarce over the whole uterus with the exception of the tubal extremities of the uterine horns. Noradrenaline concentrations were also significantly lower in late pregnancy, and significant variations occurred in different regions of the uterus, with the greatest concentrations present in the tubal extremities. At 13-16 weeks post partum, the density of innervation was variable, although the noradrenaline concentration was only slightly less than in virgin animals. Dopamine was also present in substantial quantities, but the mean concentrations remained unchanged during pregnancy.

Animals↗
PubMed1986

Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress.

Heretofore, the intracellular accumulation of sorbitol has been associated exclusively with deleterious (cataractogenic) changes in the lens. This study demonstrates a beneficial role for the sorbitol pathway in the rabbit lens, namely that of counteracting extracellular, glucose-derived, osmotic stress with the intracellular production of osmotically active sorbitol. Large and sudden increases in the extracellular glucose concentration lead to dehydration of the lens, a response that can be diminished by intracellular sorbitol and fructose production. These results are discussed in light of the impact (beneficial/detrimental) of aldose reductase inhibitors on the lens. Sugar cataract formation appears to result from continuous, rather than cyclical, activity of a pathway which normally may have a protective function in the lens.

Animals↗
PubMed1986

Effect of reduced uterine blood flow on fetal and maternal cortisol.

We have measured the changes in fetal and maternal plasma concentrations of cortisol in relation to blood gases and percent oxygen saturation during 2- and 4-h episodes of reversibly reduced uterine blood flow in sheep between 120 days gestation and term. During that period of reduced uterine blood flow there was a significant decrease in fetal arterial percent oxygen saturation (SaO2), PO2 and pH. Fetal SaO2 decreased from 59.5 +/- 3.2% to 31.8% +/- 2.8% by 15 min, 32.9 +/- 2.9% by 60 min, and 33.5 +/- 2.9% by 120 min. Fetal PO2 decreased from 3.2 +/- 0.1 KPa to 2.0 +/- 0.2 KPa by 15 min, 2.2 +/- 0.2 KPa by 60 min and 2.3 +/- 0.1 KPa by 120 min. Fetal pH decreased from 7.36 +/- 0.01 to 7.30 +/- 0.03 by 15 min, 7.27 +/- 0.02 by 60 min and 7.25 +/- 0.03 by 120 min. During the period of reduced uterine blood flow, fetal plasma concentrations of cortisol increased from 37.1 +/- 10.8 nmol/l to 53.3 +/- 9.2 nmol/l by 15 min, 49.2 +/- 11.4 nmol/l by 60 min and 43.3 +/- 9.0 nmol/l by 120 min. The greatest percentage increase in fetal plasma concentrations of cortisol occurred in fetuses of 126-139 days gestation. There was no significant change in maternal blood gases, SaO2 or plasma concentrations of cortisol. These experiments demonstrate that there is a significant increase in fetal plasma concentrations of cortisol in response to reductions in uterine blood flow from as early as 120 days gestation.

Animals↗
PubMed1986

Nasal obstruction in infancy.

It is stated frequently that human infants during the first 6-12 postnatal months can breathe only through their noses, except when crying. It has been proposed that there are anatomical reasons for the apparent inability to switch to oral breathing when the nasal airway is occluded, namely the relatively high position of the larynx and base of the tongue and the presence of a velolingual sphincter. Others, however, consider that immaturity of the central nervous system may be responsible. Partial obstruction of the nasal airway triggers reflexes which increase both the strength of subsequent inspiratory efforts and the degree of inspiratory activity in muscles involved in maintaining the patency of the upper airway (e.g., genioglossus and laryngeal abductors). Receptors in the larynx and pharynx which sense pressure reductions have been shown recently to be involved in regulating the activities of these upper airway muscles. When the nasal airway is obstructed to the point where ventilation cannot be maintained (or when it is totally occluded) the appropriate response is to switch to oral breathing. This response to nasal occlusion, usually accompanied by arousal, has been reported recently in some sleeping human infants. Preliminary observations in awake lambs show that total occlusion of the nasal airway leads to a switch to oral breathing only after considerable hypoxaemia has developed. After a few breaths, which restore the blood gas status, the mouth closes until the animal becomes hypoxaemic again. The maturational time-course and mechanisms underlying the infantile response to prolonged nasal obstruction, including the influence of sleep-states, clearly require further investigation, through necessity, in experimental animals.

Airway Obstruction↗
PubMed1986

The effects of raising intracranial pressure on breathing movements, eye movements and electrocortical activity in fetal sheep.

Extra-dural or cerebroventricular intracranial pressure was measured in 7 unanaesthetized fetal sheep (123-137 days gestation). Basal intracranial pressure was 6.7 +/- 1.7 mmHg, but there were many transient increases of pressure in association with spontaneous changes of amniotic pressure, fetal intrathoracic pressure, and particularly when the fetal nuchal muscles were active. These spontaneous increases of intracranial pressure were often associated with cessation of breathing movements and change of the electrocorticogram from low to high voltage activity. To test whether increased intracranial pressure influenced breathing movements and electrocortical activity, intracranial pressure was raised either by occluding the superior vena cava for 1 min with an implanted extravascular cuff, or by extra-dural injection of 0.3-1.0 ml of 0.9% NaCl. Increasing the intracranial pressure 5-15 mmHg by either method during low voltage electrocortical activity caused cessation of breathing movements, electro-ocular activity, and change of the electrocorticogram from low to high voltage in a significant proportion of trials. We propose that natural fluctuations of intracranial pressure caused by compression of the fetal body or skull, by body movements or by uterine activity, may cause changes in electrocortical activity and breathing movements.

Animals↗
PubMed1985

Laboratory evaluation of patients with vascular occlusive disease.

In addition to the determination of the presenting symptom of patients with peripheral vascular occlusive disease, evaluation of these patients may include the noninvasive measurements of ankle/arm pressure ratio, limb blood flow, and treadmill testing to evaluate the severity of the reduction in blood flow. We have included metabolic studies to assess the effect of this reduced blood flow in patients with stable intermittent claudication (n = 20), and with end-stage ischemia (night and rest pain) (n = 11), and in a control group without vascular disease (n = 8). No correlations were found between the resting limb blood flow, ankle/arm pressure ratios, maximum walking distance, and stated walking distance for the patients with stable claudication. Although the oxygen consumption was reduced only in the patients with end-stage ischemia, the percent oxygen extraction was increased to the same level in the patients with stable claudication and those with end-stage ischemia. Intramuscular stores of high-energy phosphates and glycogen were maintained in all groups with the lactate/pyruvate ratio increased only in the patients with end-stage ischemia. The complex interrelationships between the rate and distribution of blood flow with exercise and enzyme adaptation in patients with vascular disease make current resting hemodynamic and metabolic evaluations a poor reflection of the severity of the clinical condition within each patient group. Therefore laboratory testing may offer no advantage over clinical presentation in the overall evaluation of these patients.

Adenosine Triphosphate↗
PubMed1985

Relationship between accelerations and decelerations in heart rate and skeletal muscle activity in fetal sheep.

Accelerations in fetal heart rate have been shown to be closely related to fetal body movements and are indicative of well-being in the human fetus. We have examined the association of accelerations and decelerations in heart rate with skeletal muscle activity in 8 fetal sheep between 125 and 145 days' gestation. Accelerations/decelerations were defined as transient increases/decreases in fetal heart rate of greater than or equal to 10 beats/min. lasting for 5 s or longer. For accelerations (n = 1180), the mean duration was 18.8 +/- 1.5 s (SEM) and the mean amplitude was 25.3 +/- 1.2 beats/min; for decelerations (n = 237), the mean duration was 17.4 +/- 1.6 s and the mean amplitude was 18.7 +/- 1.0 beats/min. Electromyograms were recorded from the nuchal muscles and antagonistic muscle groups of the fetal forelimb and hindlimb. Electromyogram activity occurred during 88.4 +/- 2.8% of accelerations and 60.6 +/- 7.7% of decelerations. There was a 36.6% reduction in the number of accelerations following fetal paralysis with gallamine, but no change in their amplitude or duration. It is concluded that accelerations in heart rate are highly associated with skeletal muscle activity in fetal sheep. The majority of these occur as a result of central neuronal output rather than as a consequence of fetal movement.

Animals↗