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Biomedical subjects

A Jonzon

Publications and source records attributed to A Jonzon.

At least 37 records · Page 2Linked to original sources

Lung hyaluronan during development: a quantitative and morphological study.

Hyaluronan, an important constituent of developmental interstitium in fetal lungs, mediates cell-to-cell interactions and thereby directs migrating cells. Furthermore, because of the polyionic nature of the molecule, hyaluronan forms open, hydrated matrices that provide channels for migrating cells. This hydrated matrix undergoes contraction before birth. However, continued growth of the lung in the perinatal period requires newly synthesized hyaluronan. This study's purpose was to elucidate the changes in lung hyaluronan concentration and distribution in the perinatal period. We studied rabbits at days -6, -4, -2, -1, 0, +2, and +4 with respect to term, as well as adult rabbits. We found that hyaluronan concentration was highest in the youngest fetuses studied [682 +/- 115 micrograms/g dry wt (means +/- SD)]. However, hyaluronan concentration decreased to 129 +/- 12 micrograms/g dry wt just before birth then returned to 366 +/- 111 micrograms/g dry wt at day +4; these values were similar to adult values. We found hyaluronan staining decreased during late gestation, particularly in the interalveolar region. In the postnatal period, hyaluronan staining increased in the visceral pleura and, to a lesser extent, beneath the epithelium of the bronchioles. Hyaluronan did not reaccumulate in the interalveolar region in the postnatal period. Our data suggest a change in the predominant role of lung hyaluronan during the perinatal period. Before term, hyaluronan facilitates morphogenesis. However, hyaluronan's major role in neonatal lung is most likely in regulation of fluid balance in interstitium.

Animals↗

Intravenous injection of hypertonic NaCl solution stimulates pulmonary C-fibers in dogs.

Intravenous injection of hypertonic NaCl solution evokes reflex bradycardia and hypotension, effects thought to result from stimulation of afferent vagal endings in the lungs. To identify the afferents responsible for these effects, we recorded vagal impulses arising from endings in the lungs and lower airways of anesthetized dogs and examined the response to injection of hypertonic solutions into the pulmonary circulation. Injection of 4,800 mmol/l NaCl solution (1 ml/kg) stimulated 39 of 49 pulmonary C-fibers, their impulse frequency increasing 35-fold. Stimulation was concentration dependent, the minimum effective concentration being between 1,200 and 4,800 mmol/l. Rapidly adapting receptors were also stimulated in a concentration-dependent manner, 35 of 41 receptors being stimulated by 4,800 mmol/l NaCl solution, firing increasing fivefold. Bronchial C-fibers were not stimulated by injection into the pulmonary circulation but were by injection into the bronchial artery. Hypertonic urea solutions had qualitatively similar but smaller effects on pulmonary C-fibers and rapidly adapting receptors. The results suggest that the reflex effects of intravenous injection of hypertonic solutions result principally from stimulation of pulmonary C-fibers.

Adaptation, Physiological↗

Perinatal risk factors for inflammatory bowel disease: a case-control study.

To examine perinatal risk factors for Crohn's disease and ulcerative colitis, the authors analyzed birth records for 257 known case participants delivered from 1924 through 1957 at the University Hospital in Uppsala County, Sweden, and compared them with records for 514 controls delivered at the hospital. The two groups were matched by date of birth, sex, and either maternal age or parity. Eleven study variables were abstracted from standard forms that recorded health events during the pregnancy and the delivery hospitalization. Participants were more likely than controls to have a recorded health event (odds ratio (OR) = 4.4; 95% confidence interval (CI) 3.0-6.4). In a multivariate model, this increased risk was evident for infectious (OR = 3.8; 95% CI 2.6-5.8) and noninfectious (OR = 3.5; 95% CI 2.0-6.3) events. Perinatal health events may have contributed to 40% of the inflammatory bowel disease cases in our study. Infants from families with low socioeconomic status had greater risk of inflammatory bowel disease than did infants from families with high socioeconomic status (OR = 3.0, 95% CI 1.5-6.1). Perinatal health events and low socioeconomic status independently increased the risk of inflammatory bowel disease.

Analysis of Variance↗

Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs.

We examined the ability of rapidly adapting receptors (RARs) to monitor changes in dynamic lung compliance (Cdyn) in anesthetized spontaneously breathing dogs by recording RAR impulses from the vagus nerves. We decreased Cdyn in steps through the physiological range by briefly restricting lung expansion with an inflatable cuff around the chest and recording the response after deflating the cuff; we restored Cdyn to control by hyperinflating the lungs. Of 45 RARs, 34 were stimulated by a 40 +/- 2% reduction in Cdyn, their inspiratory discharge increasing on average more than threefold. Two-thirds of responsive RARs were stimulated by less than or equal to 20% reductions in Cdyn; in most, firing increased proportionately with lung stiffness (1/Cdyn) as Cdyn was decreased further. Stimulation by reduced Cdyn was not simply a function of the concomitant increase in transpulmonary pressure, because similar increases in pressure produced by increasing tidal volume produced smaller increases in firing. RAR stimulation was unaffected by atropine and, hence, was not dependent on neurally mediated changes in bronchomotor tone. Our results indicate that during spontaneous breathing RARs provide a signal inversely proportional to Cdyn.

Adaptation, Physiological↗

Respiratory response to adenosine in newborn lambs is modified by hypoxemia and by heat stress.

A study was made to determine whether adenosine is involved in the regulation of breathing and whether the respiratory response to injections of adenosine and its analogue L-PIA (phenylisopropyl adenosine) is modified by moderate hypoxemia or by heat stress. Unanesthetized lambs with chronically implanted catheters were used for the investigation. Intravenous injections of adenosine caused an increase in the rate of breathing lasting for 5-30 s, except during heat stress, when the rate of breathing decreased. Injection of L-PIA also increased the rate of breathing, but the effects lasted longer than after injection of adenosine. During heat stress the response to injection of L-PIA varied. Both the arterial blood pressure and heart rate decreased transiently after intravenous injection of adenosine or L-PIA, while the central venous pressure increased. Adenosine might thus be part of a positive feedback system that stimulates breathing under normal environmental conditions with or without moderate hypoxemia. The respiratory responses to injection of adenosine during heat stress are different, which might indicate that under this condition the effects of adenosine on breathing are modified by its influence on temperature control.

Adenosine↗

Airway pressures during positive-pressure ventilation with superimposed oscillations.

This study was undertaken to determine whether oscillations superimposed on a regular ventilatory pattern influence the arterial blood gases and pH and the airway pressures at adequate alveolar ventilation at the onset of inhibition of inspiratory activity. The peak, mean and end-expiratory airway pressures were therefore measured at inhibition of this activity with and without superimposition of oscillations on the ventilatory pattern. It was found that superimposed oscillations lowered the airway pressure only at a low ventilatory frequency, whereas inhibition occurred at almost equal arterial PCO2 and pH values with and without superimposed oscillations on the ventilatory pattern.

Animals↗

Pancuronium bromide does not lower airway pressures during intermittent positive pressure ventilation in young cats.

High intrapulmonary pressure is probably an important factor in the development of extra-alveolar air leaks and bronchopulmonary dysplasia during neonatal intermittent positive pressure ventilation (IPPV). Spontaneous breathing, which may be asynchronous with the ventilator as a result of hypoventilation or sometimes of the ventilatory pattern of the ventilator, can be prevented by neuromuscular blockade. During neuromuscular blockade with pancuronium bromide the central inspiratory (phrenic nerve activity) activity could be inhibited during IPPV at all ventilatory frequencies tested, but a lower arterial PCO2 and a higher pH were needed to achieve inhibition at a low frequency (15 bpm). In the present study it was observed that central inspiratory activity in cats was stimulated by intravenous injection of pancuronium bromide. In cats not subjected to neuromuscular blockade the inspiratory activity was inhibited during IPPV at all ventilatory frequencies studied. At the onset of inhibition of this activity, the arterial blood gases and pH in these animals were almost the same at all ventilatory frequencies. When ventilation was administered at a low frequency, higher peak intratracheal pressures were needed to obtain inhibition of central inspiratory activity than when high frequencies were used, both before and after neuromuscular blockade.

Animals↗

Attenuation of pulmonary afferent input by vagal cooling in dogs.

In open chest, artificially ventilated, anesthetized dogs, we examined the effect of vagal cooling on the pulmonary afferent input evoked by hyperinflating the lungs to 3 VT, recording the activity of slowly adapting pulmonary stretch receptors (PSRs), rapidly adapting receptors (RARs) and pulmonary C fibers rostral to the cooling platform. At 15 degrees C and below, input in all three types of fiber was significantly reduced, attenuation being least marked in C fibers. Between 12 degrees C and 7 degrees C, attenuation of RAR input was significantly less than that of PSRs. At 7 degrees C, virtually none of the hyperinflation-evoked increase in PSR activity and only 10% of that in RARs passed the cooling platform--indeed RAR input was less than during normal ventilation at 37 degrees C; by contrast, 40% of the hyperinflation-evoked increase in C fiber activity was still transmitted. Cooling had similar effects on C fiber input evoked by capsaicin. If reflexes are attenuated in proportion to the attenuation of afferent input, our results suggest that a hyperinflation-evoked reflex that survives vagal cooling below 6 degrees C is almost certainly triggered by C fibers.

Afferent Pathways↗

Influence of radiant heat stress on respiratory water loss in new-born lambs.

Respiratory water loss, oxygen consumption and carbon dioxide production were measured during rest and during moderate radiant heat stress in 9 healthy unanaesthetized lambs, age 4-15 days. The method used is based on an open flow-through system with a mass spectrometer for gas analyses. Respiratory water loss was 12.7 mg/kg min when the lamb was at rest and increased to 24.7 mg/kg min during heat stress. Oxygen consumption was 13.9 ml/kg min at rest and remained unchanged during heat stress. The mean rate of breathing increased from 63 to 125 breaths/min.

Animals↗

Changes in inspiratory activity after injection of adenosine and hypoxanthine in cats.

The effects of intra-arterial and intravenous injections of adenosine and hypoxanthine were investigated with special reference to respiratory variables in anesthetized young cats. Studies were made of the effects on inspiratory activity (phrenic nerve activity), heart rate, blood pressure and central venous pressure. To assess the risk of accumulation of adenosine degeneration products after several injections measurements were also made of hypoxanthine, xanthine and urate in plasma at intervals after the injections. It was found that intra-arterial and intravenous injections of adenosine increased central inspiratory activity during the first few breaths after the injection. The blood pressure and heart rate decreased slightly and central venous pressure increased slightly after the injection. Degradation of adenosine and its metabolites takes place rapidly and it is therefore unlikely that metabolites influence the results. It is concluded that adenosine causes brief stimulation of inspiratory activity.

Adenosine↗

Inhibition of phrenic nerve activity during positive-pressure ventilation at high and low frequencies.

A study was made to determine whether the ventilatory pattern, in terms of ventilatory frequency, insufflation period and end-expiratory pressure, influences the arterial blood gas level at which central inspiratory activity is inhibited, and whether further expansion of the lung changes this activity. This was accomplished by measuring arterial pH and blood gases, and intratracheal, intrapleural and transpulmonary pressures, at the setting of positive-pressure ventilation causing inhibition of phrenic nerve activity in chloralose-anaesthetized cats. Spontaneous breathing movements were prevented by muscle relaxation. Ventilatory frequencies of 15-120 breaths per minute (b.p.m.) were studied at at least two different insufflation times. A volume-controlled ventilator with a large compressible volume was used in the frequency range 15-45 b.p.m. and a constant flow respirator with a low-compressible volume in the range 45-120 b.p.m. A much lower PCO2 was needed for phrenic nerve activity to be inhibited at a ventilatory frequency of 15 b.p.m. than at higher frequencies. At ventilatory frequencies between 30 and 120 b.p.m. inhibition could be achieved at a higher PCO2, within the normal range. The inhibition of phrenic nerve activity tended to be less stable when PEEP was added during ventilation with a long insufflation period, but PEEP did not influence the arterial blood gas level at which inhibition occurred. In the lower frequency range of 15-30 b.p.m., inspiratory activity was observed with bursts at the same rate as the insufflations given by the ventilator. The intratracheal peak pressures at ventilation causing inhibition of phrenic nerve activity decreased with increasing ventilatory frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Rapidly adapting receptor activity in dogs is inversely related to lung compliance.

We examined the response of pulmonary rapidly adapting receptors (RAR's) to changes in dynamic lung compliance (Cdyn) in the physiological range. RAR impulse activity was recorded from the cervical vagus nerves in anesthetized open-chest dogs whose lungs were ventilated at constant rate and tidal volume (VT), with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. After hyperinflation to produce maximal Cdyn, RAR's were silent or fired sparsely and irregularly. Reducing Cdyn in steps by briefly removing PEEP increased firing proportionately, and RAR's began to discharge vigorously in inflation. Activity was restored to control by hyperinflating the lungs. Activity also increased when we increased inflation rate, and hence the rate of change of airway pressure (dP/dt), by reducing inflation time, keeping VT and cycle length constant. RAR's were stimulated more when dP/dt was increased by reducing compliance than when dP/dt was increased by increasing inflation rate. We conclude that RAR's are sensitive to changes in Cdyn and speculate that excitatory input from RAR's may help to maintain VT as the lungs become stiffer.

Action Potentials↗

Continuous positive airway pressure increases vagal and phrenic nerve activity in cats.

To investigate how continuous positive airway pressure (CPAP) changes the vagal nerve activity and whether CPAP alters the efferent phrenic nerve activity or the breathing pattern similarly before and after vagotomy, a study was made of vagal and phrenic nerve activity in chloralose-anaesthetized cats. In the vagal nerve, CPAP increased the mean impulse frequency during expiratory rest. The breath-related impulse frequency also increased with CPAP. With higher CPAP (greater than or equal to 0.5 kPa), the peak of breath-induced activity in the vagal nerve lasted longer than inspiration. In the phrenic nerve, the impulse frequency in the bursts increased almost linearly with CPAP irrespective of whether the vagal nerves were intact or not. The duration of the phrenic nerve bursts decreased with increasing CPAP when the vagal nerves were intact. When the vagal nerves were cut, the burst duration did not change. The rate of breathing was almost unchanged by CPAP regardless of whether the vagal nerves were cut or not. The inspiration/expiration ratio decreased with increasing CPAP when the vagal nerves were intact, but not when they were cut.

Animals↗

Alveolar deadspace during high frequency positive pressure ventilation. Influence of ventilatory pattern.

Pulmonary gas exchange was studied in association with high frequency ventilation and its relation to the duration of insufflation and end-expiratory pressure investigated. Alveolar deadspace, alveolar ventilation and the alveolar-arterial oxygen difference were obtained in cats receiving a constant minute ventilation. Alveolar deadspace increased with ventilatory frequency when a long insufflation time was used. A positive end-expiratory pressure (PEEP) decreased the alveolar deadspace in high frequency ventilation. Thus, with the low compressible volume ventilator, more efficient high frequency ventilation can be achieved with a short period of insufflation plus low PEEP.

Animals↗

A low continuous positive airway pressure induces regular breathing and increased inspiratory activity in newborn lambs.

To determine the lowest continuous positive airway pressure (CPAP) at which breathing becomes regular and to determine whether the phrenic nerve activity changes simultaneously, breathing pattern and phrenic nerve activity were studied in spontaneously breathing newborn lambs at various levels of CPAP. A CPAP of 0.25 kPa decreased the variability of phrenic burst interval, i.e. made the breathing regular. This CPAP also increased the mean impulse frequency within the phrenic nerve bursts, indicating greater inspiratory activity. A high CPAP did not offer any further advantages to the breathing pattern or to the inspiratory activity.

Animals↗

Functional residual capacity and ventilatory pressures during positive-pressure ventilation at high frequencies.

The functional residual capacity (FRC) was measured in cats by the nitrogen washout technique during positive-pressure ventilation. Frequencies of 60 and 100 b.p.m. were used with insufflation periods of 20% and 35% of the ventilatory cycle, without and with a positive end-expiratory pressure. The higher frequency combined with the shorter insufflation period gave FRC close to that obtained during spontaneous breathing. The lower frequency and the longer insufflation period always gave greater FRC values. A further increase in FRC of about 23-27% was obtained after application of a positive end-expiratory pressure of 0.5 kPa. Adequate ventilation was achieved with small intratracheal and intrapleural pressures at all settings used.

Animals↗