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Biomedical subjects

R Harding

Publications and source records attributed to R Harding.

At least 163 records · Page 9Linked to original sources
PubMed1985

The role of cardioplegic solution buffering in myocardial protection. A biochemical and histopathological assessment.

The advantages of buffering cardioplegic solutions to improve adenosine triphosphate preservation and postarrest hemodynamic function have been previously promoted. We evaluated the benefit of histidine buffering (195 mmol/L) in a low sodium (27 mEq/L) cardioplegic solution (Roe's) in a canine model of multidose cardioplegic arrest. Four solutions, two unbuffered (K+ = 10 mEq/L and K+ = 30 mEq/L) and two buffered (K+ = 10 mEq/L and K+ = 30 mEq/L), were tested in four groups of dogs for a 4 1/2 hour arrest period followed by 1 hour of reperfusion. Use of the unbuffered solution resulted in a drop in myocardial adenosine triphosphate from 29 +/- 1 mmol/kg (mean +/- standard error of the mean) (K+ = 30 mEq/L) and 28 +/- 2 mmol/kg (K+ = 10 mEq/L) to 8 +/- 2 mmol/kg and 7 +/- 2 mmol/kg, respectively, during the arrest period. In both buffered groups, adenosine triphosphate remained at preischemic levels during the entire arrest period. Myocardial glycogen followed the same pattern as adenosine triphosphate in the buffered groups. Lactate production was markedly elevated in all groups during ischemia. Postarrest hemodynamic function, as assessed by intraventricular isovolumic developed pressure measurements, was better (p less than 0.05) in the buffered low-potassium group than in the other three groups. The extent of myocardial necrosis, measured by triphenyl tetrazolium staining and confirmed by electron microscopy, was minimal (2% +/- 1% of biventricular mass) in the buffered low-potassium group, significantly greater (7% +/- 2% and 10% +/- 2%) in the unbuffered high-potassium and low-potassium groups, respectively, and highest (35% +/- 9%) in the buffered high-potassium group. These findings indicate that significant buffering capacity (similar to that of blood) in a crystalloid cardioplegic solution can be effective in preserving myocardial adenosine triphosphate stores, improving postarrest contractile function, and minimizing myocardial necrosis, provided the combination of high extracellular potassium and high pH levels is avoided.

Adenosine Triphosphate↗
PubMed1984

The influence of acute hypoxia and sleep states on the electrical activity of the cerebellum in the sheep fetus.

The experiments were designed to examine (1) the effects of acute hypoxia and (2) the influence of sleep states on the electrical activity of the cerebellum in the fetus. Five fetal sheep were instrumented between 106 and 133 days of gestation and survived in utero until term (140-146 days). Insulated stainless steel electrodes (75 microns diam.) were introduced into the cerebellar cortex and cemented in place. Electrodes were also implanted into 4 fetuses to monitor the electrocorticogram, rapid eye movements and the EMG of the dorsal neck (nuchal) muscles. Recordings of cerebellar activity were made for 252 h in 4 fetuses. The recordings were derived from many units (probably Purkinje cells) with a high level of basal discharge. The mean firing frequency was related to fetal sleep state. The highest frequencies coincided with episodes of rapid eye movements with low-voltage electrocortical activity and the lowest occurred during high-voltage electrocortical activity when rapid eye movements are absent. Acute hypoxaemia (fetal pa O2 6-10 mm Hg for up to 30 min) abolished rapid eye movements and caused a marked reduction in cerebellar activity. High-voltage electrocortical activity and nuchal EMG activity were maintained indicating that the effects of hypoxia on the cerebellum were not due simply to a general CNS depression. Cerebellar neural activity returned to normal at the termination of the hypoxic stimuli demonstrating that fetal Purkinje cells can withstand short episodes of severe hypoxia.

Animals↗
PubMed1984

The regulation of flow of pulmonary fluid in fetal sheep.

The flow of fluid within the trachea of fetal sheep (121-135 days) has been measured using a newly developed flowmeter. The flowmeter, which is basically a miniature servo-controlled peristaltic pump, is connected in series with an extra-corporeal tracheal loop. Integrated tracheal flow was measured for periods of at least 8 h in 5 control fetuses during which we determined its relationship to fetal breathing movements detected by EMG's of inspiratory muscles or tracheal pressure fluctuations. The overall flow of fluid away from the lungs was 14.4 ml/h; on average outward flow was 5.3 times greater during episodes of breathing movements than during apnea. Interruption of the motor innervation of the larynx in 5 fetuses led to a 25% reduction in mean overall flow and, compared with control fetuses, there was a reduction in net flow associated with breathing movements and an increased flow during apnea. These findings suggest that tracheal flow is normally retarded by a laryngeal mechanism during apnea, giving rise to an elevated pressure within the trachea and probably resulting in increased pulmonary distension. Paralysis of the fetus with gallamine triethiodide reduced the flow of liquid from the lungs and abolished variations in flow rate related to fetal electrocortical states.

Animals↗
PubMed1984

Development of myometrial electrical activity during the first half of pregnancy in the sheep.

Uterine myoelectrical activity was recorded in seven pregnant sheep covering the period between 13 and 75 days post-coitum. Activity in the myometrium was present at day 13 and took the form of intermittent spikes of low amplitude. Bursts of spikes of irregular duration became noticeable between days 25 and 40 but most were not coordinated throughout the myometrium. Coordinated bursts of myoelectrical activity, which could be recorded at several sites simultaneously, first appeared between 40 and 65 days. These bursts had similar characteristics to the myoelectrical activity associated with uterine contractions during the last third of gestation. The myoelectrical activity showed a progressive increase in amplitude during the first half of gestation. There was no relationship between plasma progesterone levels and the increase in amplitude or appearance of coordinated bursts of uterine activity.

Animals↗
PubMed1984

Ingestion in fetal sheep and its relation to sleep states and breathing movements.

Swallowing was recorded electromyographically in unanaesthetized fetal sheep in utero during the last third of gestation. In control fetuses bouts of swallowing were, on average, 2.0 min in duration and occurred at intervals of 2.31 h. Swallowing bouts were associated with a low-voltage electrocorticogram, eye movements and, in 82% of instances, with phasic activity in the dorsal neck muscles. These data indicate that fetuses are not in quiet (non-rapid eye movement; n.r.e.m.) sleep when swallowing and also suggest that they are not in r.e.m. sleep as conventionally defined; we consider that fetuses may be in a state of heightened activity resembling wakefulness. Swallowing bouts were always accompanied by fetal breathing movements. When a swallow coincided with an inspiratory effort the diaphragm was briefly inhibited. Evidence was obtained that bouts of fetal ingestive activity were not dependent upon outpourings of fluid from the lungs and were not significantly influenced by volume information from the gastric compartments.

Animals↗
PubMed1984

Composition and volume of fluid swallowed by fetal sheep.

Oesophageal cannulations were performed in seven fetal sheep between 109 and 128 d of gestation. Fluid swallowed by the fetuses was collected externally and periodically returned to the fetal stomach by a peristaltic pump. The volume of fluid swallowed daily was calculated from the movement of water in a parallel pump circuit. Samples of oesophageal fluid were removed from the collection bag at the same time as tracheal and amniotic fluid samples. Oesophageal fluid was very viscous and was usually intermediate in colour between tracheal and amniotic fluids. After reduction of viscosity by dithiothreitol, the compositions of the three fluids were analysed. Mean concentrations of Na+, Cl- and protein, and mean osmolarity of oesophageal fluid, were intermediate between values obtained in tracheal and amniotic fluids. [K+] was often greater in oesophageal fluid than would be expected by the relative contribution of tracheal and amniotic fluids as indicated by [Na+] and [Cl-] in the three fluids. It is suggested that the high viscosity of oesophageal fluid and its relatively high [K+] may result from fetal salivary secretions. Ionic concentrations in individual sets of samples show that the proportions of tracheal and amniotic fluids swallowed by the fetus are variable from day to day. The mean daily volumes of fluid swallowed by the seven fetuses ranged from 98 to 577 ml, and are in agreement with previously published data.

Amniotic Fluid↗
PubMed1984

Function of the larynx in the fetus and newborn.

The muscles of the larynx function as a part of the respiratory system before birth, and like other respiratory muscles, have experienced considerable use by the moment of birth. In late fetal life the larynx appears to influence the outward flow of pulmonary liquid and thus may play a role in lung development. Immediately after birth and in cases of neonatal lung disease, elevated pressures within the airways during expiration, probably a result of laryngeal adduction, are involved in the maintenance of FRC. This mechanism is also present, to a lesser degree, in normal ovine (and probably human) neonates during quiet sleep. Whether it exists in other species remains to be established. Expiratory resistance of the larynx is under vagal control, and pulmonary stretch receptors are the likely sensors. Species differences apparently exist in the means by which expiratory airflow is retarded. These may be due in part, however, to the widespread use of anesthetic agents that selectively depress the activity of laryngeal adductor muscles. There is clearly a need for wider use of techniques involving chronic instrumentation, particularly in the neonatal period. Because the upper airway is involved in the regulation of tidal airflow, it also seems vital that the airway remains intact wherever possible. In addition to controlling airflow, the larynx is an important sensory organ, protecting the lower airways from invasion by potentially harmful substances, e.g. during suckle feeding and regurgitation. In the neonate, laryngeal stimulation may result in prolonged respiratory arrest. Although there is some evidence that longer apnea can be elicited in the neonate than in the adult, the use of anesthesia, which may more strongly depress respiration in the young, complicates the issue. As yet, there are no firm grounds for explaining these findings, at either a peripheral or central level. Defensive mechanisms, including arousal, swallowing, and circulatory changes to cope with hypoxemia, are well established at birth. The healthy neonate would seem well equipped to survive entry of liquids into the larynx. However, it is not inconceivable that, under certain circumstances and in the absence of anesthesia, substances entering the larynx could trigger prolonged apnea or cardiac arrest.

Aging↗
PubMed1984

Decreased uptake of exogenous substrates following graded muscle stimulation.

An exercising in vivo canine hindlimb model was used to assess the pattern of exogenous substrate delivery and uptake as a function of contraction frequency. The limb was stimulated to contract at 0, 4, 8, 12 8, 4, and 0 Hz for 10-min periods. Blood flow was proportional to stimulatory frequency. Oxygen consumption increased to a maximum at 12 Hz and subsequently declined. Glucose, free fatty acid, and lactate uptakes decreased despite increased deliveries and maintained arterial concentrations at 12 Hz. At this point there was a net release of glycerol and lactate from the muscle. Microvascular shunting was not the cause of decreased exogenous substrate uptake at 12 Hz. A switch from exogenous to endogenous muscle substrates occurred with the onset of decreased substrate uptake. The mechanism that facilitates this switch from exogenous to endogenous substrates remains unknown.

Animals↗
PubMed1984

The effects of myometrial activity on fetal thoracic dimensions and uterine blood flow during late gestation in the sheep.

We wished to investigate mechanisms by which non-labour contractions of the uterus influence fetal sleep states and respiratory activity during late pregnancy. The relationship between the dimensions of the fetal chest and uterine contractions was examined in 5 pregnant sheep. The dorso-ventral dimension at the level of the xiphisternum (3 fetuses) decreased, on average by 4.4-9.4% while increases of 16.6-18.7% were seen in the transverse dimension (4 fetuses). Blood flow in a middle uterine artery was monitored using a Doppler technique in 5 pregnant sheep. Non-labour uterine contractions were accompanied by mean reductions of 6.5-12.7% in blood flow. Postural adjustments by the ewe also influenced uterine blood flow. A mean increase in blood flow of 5.9-12.0% followed a change from standing to lying; standing caused a mean reduction of 5.9-11.8%. We conclude that the influence of uterine contractions on the fetus is likely to be complex, involving distortion of the body and alterations in utero-placental haemodynamics.

Animals↗
PubMed1984

Relationship between electrical activity of the uterus and surgically isolated myometrium in the pregnant and nonpregnant ewe.

Rhythmic contractions occur in the sheep uterus at oestrus and during pregnancy from about 65 days to term (145 days). To define factors responsible for these contractions we have examined and quantified the degree of synchronization of electrical activity in the uterus and isolated segments of myometrium in 3 types of experiments. In the first, a segment of myometrium was totally separated from the uterus. After a period of 9-16 days the isolated tissue developed a typical pattern of uterine activity which showed no significant degree of synchronization with EMG bursts in the body of the uterus. During labour, the isolated tissue showed changes in activity similar to those observed in the uterus. In the 2nd experiment, the tubal end of one of the uterine horns was severed from the uterus, but a connection was retained with the uterus via the oviduct and ovarian blood vessels. Activity in the partly isolated segment remained in synchrony with the uterus. In a 3rd experiment, impulse propagation through nerves and smooth muscle to the tip of a horn was disrupted by severing 'the tip' from the uterus while its blood supply from the ovarian vessels was retained. The blood vessels were momentarily frozen, and denervation confirmed by monoamine histofluorescence. In 5 out of 6 animals the operated tissue showed activity that was not synchronous with the rest of the uterus. These data indicate that: (1) isolated uterine muscle in vivo has rhythmicity resembling that of intact myometrium and (2) systemic or local circulating factors are not responsible for synchronizing uterine activity before parturition, although circulating factors do play a major role in increasing the uterine activity which occurs at parturition and at oestrus, and (3) hydraulic continuity between different regions of the uterus is not essential for maintaining co-ordinated activity.

Adrenergic Fibers↗
PubMed1984

A clinical trial of blood and crystalloid cardioplegia.

Although experimental studies suggest that blood cardioplegia provides better protection than crystalloid cardioplegia, clinical studies have been inconclusive. Ninety patients undergoing coronary bypass grafting were randomized to receive either blood (n = 43) or crystalloid cardioplegia (n = 47). The incidence of perioperative myocardial infarction was lower with blood cardioplegia (blood, n = 0; crystalloid, n = 5; p = 0.06), and the maximum MB isoenzyme of creatine kinase was significantly less with blood cardioplegia (blood, 26.3 +/- 12.6 U/L; crystalloid, 35.6 +/- 17.0 U/L, mean +/- standard deviation; p less than 0.02.) Sixty patients (blood cardioplegia, n = 28; crystalloid cardioplegia, n = 32) had more sensitive measurements to assess the metabolic response to aortic occlusion and to compare the metabolic and functional recovery from the operation. Coronary sinus blood flow (by the continuous thermodilution technique) was significantly lower after cross-clamp removal with blood cardioplegia (blood, 160 +/- 100 ml/min; crystalloid, 220 +/- 120 ml/min; p less than 0.05), indicating less reactive hyperemia. The cardiac production of lactate was significantly less with blood cardioplegia during aortic occlusion (blood, -0.5 +/- 0.9 mmol/L; crystalloid, -0.9 +/- 0.9 mmol/L; p less than 0.05) and immediately after aortic declamping (blood, -0.2 +/- 0.4 mmol/L; crystalloid, -0.7 +/- 0.7 mmol/L; p less than 0.01). Thermodilution cardiac output measurements permitted calculation of the left ventricular stroke work index, and nuclear ventriculograms permitted calculation of the left ventricular end-diastolic volume index and end-systolic volume index. Myocardial performance, systolic elastance, and diastolic compliance were determined from volume loading studies (250 to 500 ml colloid) performed 2 to 4 hours postoperatively. Myocardial performance (the left ventricular stroke work index-left ventricular end-diastolic volume index relation) and systolic elastance (the systolic blood pressure-left ventricular end-systolic volume index relation) were significantly better with blood cardioplegia (p less than 0.01 by multivariate analysis); diastolic compliance (the left atrial pressure-left ventricular end-diastolic volume index relation) was similar. Blood cardioplegia reduced ischemic injury, decreased anaerobic metabolism during arrest, and permitted better functional recovery. Blood cardioplegia provides superior protection for elective coronary bypass grafting and may improve the clinical results in patients with unstable angina and in other high-risk patients.

Anti-Arrhythmia Agents↗
PubMed1984

Effect of hypoxia on the excitability of two cranial reflexes in unanaesthetized fetal sheep.

In fetal sheep acute hypoxia causes a decreased incidence of breathing movements and motor activity, and the excitability of polysynaptic reflexes in the hindlimbs is depressed. To determine whether this inhibitory effect extends to other areas in the fetal CNS, we have studied the effect of hypoxia on two reflexes with cranial pathways. The digastric (jaw opening) reflex was elicited by stimulation of the dental nerve through a pair of stainless steel electrodes implanted into the mandible (4 fetuses). The thyroarytenoid muscle of the larynx was reflexly activated by stimulation of the superior laryngeal nerve by a cuff electrode (4 fetuses). Low level stimulation at 1.5-2 X threshold was repeated at approximately 2 min intervals for 3-4 h; the stimulation did not alter the pattern of electrocortical activity, breathing movements, or cause arousal. The amplitude of the digastric reflex was greatest during low voltage electrocortical activity; conversely, the amplitude of the thyroarytenoid reflex was greatest during high voltage electrocortical activity. Isocapnic hypoxia lasting 30-60 min (16 trials), in which the PaO2 was reduced to 12-14 mmHg, did not reduce the amplitude of either reflex. The reduction of thyroarytenoid reflex amplitude which normally occurred during low voltage electrocortical activity was not present during hypoxia. These experiments show that the inhibitory effects of hypoxia on spinal reflexes, breathing movements and motor activity do not include these cranial pathways.

Animals↗
PubMed1984

Perinatal development of laryngeal function.

The resistance of the upper airway is strongly influenced by the action of opposing sets of laryngeal muscles. Expiratory airflow may be retarded by active adduction of the arytenoid cartilages or by a reduction in the activity of abductor muscles. In developing sheep the adductor muscles appear to represent the principal means by which lung recoil is opposed. This mechanism, which is most pronounced during non-rapid-eye-movement sleep, is regulated by afferent traffic from the lungs. In fetal sheep the laryngeal muscles are also influenced by breathing movements and sleep states. The adductor muscles are normally tonically active during non-rapid-eye-movement sleep when rhythmical breathing movements are absent. It is possible that this activity is at least partially responsible for elevated tracheal pressures and depressed flow of tracheal fluid during fetal apnea. This hypothesis has been tested by observing the effects of fetal paralysis and recurrent laryngeal nerve section. These experiments suggest that in the fetus near term the larynx makes a major contribution to upper airway resistance and hence to the maintenance of pulmonary expansion which has been shown to influence lung development.

Airway Resistance↗
PubMed1983

Fetal and maternal influences on arterial oxygen levels in the sheep fetus.

Continuous recordings of arterial oxygen tension (PaO2) and percent oxygen saturation (SaO2) were made in 8 instrumented fetal sheep during late gestation. Fetal behavioural states were monitored from recordings of rapid eye movements, the electrocorticogram, and the nuchal electromyogram (EMG). In addition, fetal breathing and swallowing movements and uterine motility were measured using EMG techniques. Variations in PaO2 and SaO2 were related to fetal muscular activity, non-labour uterine contractions and maternal postural changes. Significant reductions in the variability of PaO2 and SaO2 were brought about in 7 of the 8 fetuses by skeletal muscle paralysis. Variation was further reduced in each fetus by paralysis of the myometrium by a beta-adrenergic agonist. Remaining variations were largely attributable to postural changes by the ewe. It is concluded that fetal skeletal muscle activity contributes to reduced amounts of oxygen in fetal arterial blood, although the mechanism by which this occurs has not yet been identified.

Animals↗
PubMed1982

Electromyographic activity of the nonpregnant and pregnant sheep uterus.

Myometrial electromyograms were studied in nonpregnant ewes, pregnant ewes throughout the second half of gestation, and during labor and delivery in normal spontaneous vaginal delivery and premature delivery induced by the continuous infusion of synthetic adrenocorticotropin 1-24, 1 microgram x h-1, to the fetus at 120 and 130 days' gestation. The bursts of electromyographic (EMG) activity during estrus were very similar to those seen in the pregnant ewe in the second half of gestation. In the second half of gestation, the bursts of EMG activity lasted a mean of 6.7 minutes and occurred at intervals of 54.7 minutes in utero, without an incision for fetal instrumentation, and were 7.2 minutes in duration, occurring every 46.6 minutes when the uterus had been incised. EMG activity occurred simultaneously at most recording sites within the uterus. There was no evidence to support the view that a uterine pacemaker exists with a fixed location. As delivery approached, the mean duration of each EMG burst began decreasing more than 24 hours before delivery, and the frequency of the bursts increased, demonstrating that the recording of uterine electromyograms provides a precise and sensitive method for the study of the early changes that lead to labor and delivery.

Animals↗