The effect on heart rate and facial skin temperature of wearing respiratory protection at work.

Twelve New Zealand workers from a range of occupations were studied to investigate the effect of wearing air-filtering respiratory protection on heart rate (HR) and facial skin temperature (Tlip and Tcheek) whilst working. All variables were measured continuously during simulated and actual work. The former allowed physiological measurements to be undertaken during the physical activities carried out during the work task without respirators and without exposure to hazardous airborne substances. Mean heart rates in subjects moving without respirators ranged from 75 to 94 beats/min and from 77 to 98 beats/min during respirator use at work. Mean skin temperature under the mask (Tlip) increased in 11 of the 12 subjects while using respirators (range 1.2-4.8 degrees C) but Tcheek only increased in four (range 0.6-1.5 degrees C). The use of simulated work tasks in the experiment was a compromise. The heart rate data from the real and simulated work indicated that effort and workload, though not identical, were similar. The increase in skin temperature under the mask may account for the reluctance of individuals to wear respiratory protection at work. This region of the face is very thermosensitive.

Progressive myelopathy and neuropathy in New Zealand Huntaway dogs.

AIM: To investigate the nature and cause of a progressive ataxia in three 20-month-old Huntaway dogs that were litter mates. METHODS: Affected dogs were examined before they were humanely killed and submitted to necropsy. Selected formalin-fixed tissues were examined by light and electron microscopy. RESULTS: The lesions were those of axon and myelin degeneration within sensory, proprioceptive and motor tracts of the spinal cord and to a lesser degree some peripheral nerves. CONCLUSION: A progressive myelopathy and neuropathy, tentatively described as a central-peripheral distal axonopathy, was present in all 3 dogs. The cause was not determined but was likely to be either genetic or nutritional. CLINICAL RELEVANCE: In the early stages of this disease, careful examination may be necessary to distinguish the signs of ataxia from orthopaedic disease such as hip dysplasia. Affected animals are unlikely to be of use as working dogs.

The myocardial effects of fenoterol, isoprenaline and salbutamol in normoxic and hypoxic sheep.

Three groups, each of four sheep, were randomly allocated under blinded conditions to receive the beta-adrenoceptor agonists, salbutamol, fenoterol or isoprenaline, in doses of 0.5, 2, 8, 32 and 128 micrograms/kg intravenously at 15-minute intervals. A separate group of four animals received equal volumes of saline. Heart rate was recorded immediately prior to each drug administration and serum potassium was measured. Three to 4 days later the experiment was repeated during induced systemic hypoxia and the animals then necropsied. All the agonists produced significant increases in heart rate. During hypoxia, lower heart rates were recorded than in the normoxic experiments. Under conditions of hypoxia, all the beta-agonists produced significant hypokalaemia. Sterile saline had no effect on either heart rate or serum potassium levels. At necropsy, myocardial lesions were found in animals receiving all three beta-agonists. Subendocardial haemorrhage was consistently seen in all animals receiving fenoterol. Multifocal myonecrosis of 3-4 days duration was present in the left ventricle of all animals receiving fenoterol, in two receiving isoprenaline and in two receiving salbutamol. The lesions were most severe in the papillary muscle and were visible grossly in one animal given fenoterol and one given isoprenaline. No lesions were found in the control animals.

The effects of sympathomimetics on the cardiovascular system of sheep.

1. Sheep hearts have been used to study the effects of beta-adrenoceptor (beta-AR) agonists in order to better understand the effects of common asthma treatment drugs on heart rate, cardiac power output and cardiac pathology. Hearts have been examined both in vivo and in vitro. 2. In whole anaesthetized sheep, isoprenaline, fenoterol and salbutamol induced dose-dependent increases in heart rate. Hypokalaemia in response to salbutamol was accentuated in hypoxia. Many of these hearts showed significant myocardial lesions. Hypoxia alone caused no significant cardiac response. 3. As expected, the beta 1-AR agonist dobutamine caused dose-dependent increases in heart performance (heart rate and cardiac power output). Both responses were blocked by metoprolol and propranolol. The beta 2-AR agonist salbutamol caused dose-dependent increases in heart rate and although cardiac output increased, cardiac power output remained unchanged as a consequence of the fall in peripheral resistance. The heart rate changes were blocked by metoprolol. Importantly, propranolol blocked both the heart rate response and the fall in peripheral resistance. 4. Isolated atrial strips showed a right shift of their dose-response curve to isoprenaline in the presence of the highly selective beta 2-AR antagonist ICI 118,551 at concentrations above 1 x 10(-8) mol/L. 5. We conclude that the sheep heart shows many pharmacological characteristics of the human heart which makes it a good pharmacological model in addition to its being amenable to many common techniques available for humans.

Physical determinants of bronchial mucosal folding.

It has recently been proposed, on the basis of a theoretical analysis, that the folding of the mucosa provides a significant component of airway stiffness. The model predicted that the stiffness of an airway was directly related to the number of epithelial folds that developed. In this study we examine the possibility that the folding pattern is determined by the physical requirements that the folding membrane must stay within the boundary of the smooth muscle wall, that the submucosal mass is constant, and that the strain energy of the folding membrane is the minimum possible within the geometric constraints. Model predictions are compared with morphometric data from the noncartilaginous airways of 17 sheep lungs. The data are in agreement with our predictions, which are based on the assumption that the folding membrane thickness is proportional to the submucosal thickness (in a fully dilated airway). The outcome of this analysis is that the increase in intrinsic stiffness of the folding membrane resulting from the increased thickness outweighs the decrease in stiffness conferred by the fewer folds required by the thicker submucosa. It is suggested that the increase in folding membrane thickness observed in asthma could be viewed as a protective mechanism that tends to reduce hyperresponsiveness.

Tensile stiffness of ovine tracheal wall.

The epithelial folding that occurs during bronchoconstriction requires that the pressure on the muscle side of the folding membrane be greater than that on the lumen side. The pressure required for a given level of folding depends on the elastic properties of the tissue and on the geometry of the folding. To quantify the elastic properties, uniaxial tensile stiffness of the tracheal inner wall of nine sheep was measured in two directions: parallel to the tracheal axis and circumferentially. The tissue showed anisotropic behavior, being approximately three times stiffer longitudinally than circumferentially. Histological examination showed that collagen in the lamina propria was randomly arranged, whereas there were straight elastin fibers aligned with the tracheal axis. This observation could explain the observed elastic anisotropy. Mechanical removal of the epithelium had no effect on tensile stiffness. It was also found that the tissue was under tension in situ. When a strip was excised, its length decreased by > or = 30%. After allowing for the systematic errors inherent in this experiment, the in situ circumferential tensile stiffness is estimated to be > or = 20 kPa. If the equivalent tissue in the bronchioles has the same tensile stiffness as that in the trachea, the forces required to fold the membrane are significant at small transbronchial pressure differences and increase in the presence of membrane thickening such as that seen in asthma.

Severe obesity: effects on foot mechanics during walking.

The purpose of our study was to determine the effects of severe obesity on the foot mechanics of adult females. Twenty-nine adult females between the ages of 20 and 48 years volunteered as subjects for this investigation. The subjects were separated into a severely obese (O) group (body mass index = 41.14 +/- 2.61; N = 16) and a normal weight control group (body mass index = 20.84 +/- 0.47; N = 13). A Locam camera (100 Hz) positioned perpendicular to the subjects' posterior aspect was used to film the rearfoot movement of the subjects during the final 15 sec of a 10 min treadmill walk. The O group had a significantly greater touchdown angle (P = .05), more total eversion range of motion (P = .001), and a faster maximum eversion velocity (P < .001). Moreover, analysis of dynamic foot angles indicated that the O group had significantly (P = .003) more forefoot abduction. Finally, anthropometric data revealed statistically different (P < .001) Q angle measurements between the O and control groups. The results of this study suggest that severely obese females have significantly greater rearfoot motion, foot angle, and Q angle values than normal weight females.

Etiologic factors associated with patellofemoral pain in runners.

The purpose of this study was to extend our knowledge of running related injuries by determining whether relationships exist between selected anthropometric, biomechanical, muscular strength and endurance, and training variables and runners afflicted with patellofemoral pain (PFP). Specifically, the objectives of this study were to examine differences in selected measures between a non-injured control group (C) of runners (N = 20) and a group of injured runners (INJ) diagnosed by an orthopedic surgeon as having PFP (N = 16). High speed photography, a force platform, and isokinetic dynamometry were used to determine rearfoot motion, ground reaction forces, and knee muscular strength and endurance. Stepwise discriminant function analyses were performed on the anthropometric, biomechanical, and muscular strength and endurance variables. Q angle was a significant discriminator (P less than 0.01) between the INJ and C groups. The muscular endurance data revealed several significant discriminators with the INJ subjects being weaker in knee extension endurance. Kinetic analysis revealed several significant discriminators whereas rearfoot movement variables were not good discriminators between the groups. The training data revealed that the INJ group ran significantly less (P less than 0.01) miles.wk-1 than the C group. Our results suggest that Q angle is a strong discriminator between runners afflicted with PFP and non-injured runners. In addition, several muscular endurance and kinetic variables may also be important components of the etiology of PFP.

Lung reflexes and receptor activity in a rabbit model of pulmonary fibrosis.

Our objective was to see if activity of individual slowly and rapidly adapting pulmonary receptors was changed by pulmonary fibrosis. Diffuse interstitial lung fibrosis of several weeks' standing was induced in 8 rabbits. They displayed changes in lung mechanics and patterns of breathing, when compared to control rabbits, similar to those seen in patients who develop pulmonary fibrosis. Lung reflexes in the fibrotic rabbits were more profoundly changed than eupneic breathing in a way that could be interpreted as slowly adapting receptor activity, which was increased, being overpowered by a prepotent input from pulmonary rapidly adapting receptors. An increase in number of active rapidly adapting receptors was found in the fibrotic rabbits during direct vagal recording. We have demonstrated that pulmonary receptor activity is changed by lung fibrosis. It may be that these changes in receptor activity produce conflicting respiratory drives that could result in the sensation of dyspnea.

Airway hypersensitivity induced by Ascaris suum extract in New Zealand Romney sheep.

Sheep from local farms with and without previous exposure to pigs were tested for their skin and airway responses to a commercial Ascaris suum antigen. There was an immediate reaction to intradermal injection of the antigen in 90% of 101 sheep. A bronchial provocation test by aerosol of the same antigen was undertaken on 43 of the sheep with a positive skin reaction. About 70% of sheep showed an immediate airway response to the antigen as an aerosol, reflected as a significant increase in airway resistance and/or decrease of dynamic lung compliance. The mean peak airway resistance and mean lowest dynamic lung compliance were 165% above and 61% below their baselines, respectively. No significant changes were recorded when the same animals were given an aerosol of phosphate buffered saline. Similarly, no correlation was found between the degree of skin reaction and the magnitude of bronchoconstriction (p>0.05). The sheep with previous exposure to pigs showed no significant differences in airway responses to antigen challenge, although they showed significantly greater skin reactions than those without exposure to pigs. These results indicate that the majority of Romney sheep in the Manawatu have a natural skin and airway sensitivity to A. suum antigen and may therefore be used as an animal model to study human airway hypersensitivity. The origin of this sensitivity has yet to be determined.

In vitro tracheal mechanics by nuclear magnetic resonance imaging.

Images of rabbit tracheal cross sections were obtained at a series of transmural pressures ranging from 22 to -95 cmH2O by use of a nuclear magnetic resonance imaging microscope. The excised, washed tracheas were immersed in a solution of phosphate-buffered saline made up in deuterium oxide (D2O, pH 7.3). The images are maps of proton density in the image slice (2.5 mm thick). All but one series of images showed a collapse process in which the trachealis muscle invaginated asymmetrically, i.e., the muscle appeared to favor one side of the cartilage ring system more than the other. The connecting tissue between the cartilage rings appeared to be more compliant than the rings themselves, thus suggesting that the tracheal lumen became corrugated at negative pressures. In the plane of a cartilage ring, the lumen appeared to remain patent at pressures as low as -95 cmH2O. However, between rings, where the tracheal wall was more compliant, the lumen appeared to be totally occluded at -53 cmH2O. Lumen areas in both the plane of the cartilage rings and in a plane between rings were measured from each series of printed images for six tracheas. These measurements, when normalized, averaged, and plotted against transmural pressure gave asymptotic logarithmic compliances (n1 in the model of Lambert et al., J. Appl. Physiol. 52: 44-56, 1982) of 1.2 +/- 0.4 and 20 +/- 7 for the interring and ring regions, respectively. These values are greater than the critical value of 0.5 (J. Appl. Physiol. 62: 2426-2435, 1987) and are thus consistent with wave speed flow limitation being possible anywhere in the trachea during forced expiration.

The functional significance of the sympathetic innervation of mucous glands in the bronchi of man.

1. Pieces of human bronchi, from lung resected for carcinoma of the bronchus, were mounted in Ussing chambers and given [35S]sulphate as radiolabelled precursor of mucous glycoproteins (mucins). The release of 35S, bound to macromolecules, into the luminal half-chamber was used as an index of mucin secretion. 2. Noradrenaline, at concentrations of 1, 10 and 100 microM, was given into both halves of the Ussing chamber. At the lowest concentration, noradrenaline failed to change mucin output, but at the two higher concentrations it stimulated output. 3. In other experiments the sympathetic nerves in the bronchial wall were labelled with 5-hydroxydopamine and examined under the electron microscope. The distances between adrenergic nerve varicosities and submucosal glands were measured; some sympathetic nerve varicosities were seen within 1 microns of gland cells. 4. A simple mathematical model for the diffusion of noradrenaline was used to predict the concentrations of the transmitter likely to result at different distances from a nerve if one or more vesicles of noradrenaline were released. 5. The model predicts that the release of a single large vesicle of noradrenaline is likely to generate an effective concentration of transmitter provided that the nerve is within 1 micron of the target cell.

The effect of hypoxia on the number of amine-containing cells in the lung of the adult rat.

Adult rats of Wistar and Sprague Dawley strains were exposed to a 21-day period of hypoxia (10% O2). At the end of this period, the hypoxic animals and paired controls were anaesthetised, dissected and tissues were taken for light microscopy. All the hypoxic animals had an increased haematocrit, right ventricle weight and carotid body size when compared with controls. The Grimelius method was used to demonstrate argyrophil structures in the lung. This method stained the amine-containing cells of the epithelium, mast cells and nerves. Mast cells associated with the pulmonary vasculature were increased in number in the hypoxic animals. Single epithelial argyrophil cells were more frequent than those in groups. In control animals the groups of cells only rarely contained more than 5 cells. In the Wistar strain there was no significant difference in the number of argyrophil cells between the control animals and those exposed to chronic hypoxia. However, in the Sprague Dawley rats, the numbers of cells, both single and in groups, were significantly increased following 3 weeks chronic hypoxia. The cell groups were also larger in the hypoxic animals, with up to 12 cells per section.

Amine-containing cells of the lung.

In many vertebrates, including mammals, there are amine-containing cells in the walls of the airways and the lungs. Despite a plethora of names for these cells, there is a general agreement about their structure. They occur singly or in groups (NEBs), but the functional distinction between the two types of distribution is uncertain. In spite of ultrastructural similarities, the cells may be physiologically heterogenous. The cells are characterised by their staining characteristics and content of electron-dense-core vesicles, which are believed to contain a biogenic amine. They also have additional cytoplasmic features common to other sensory paraganglia. They may be more numerous in certain species and also in the neonate. The NEBs may be innervated with afferent and/or efferent nerves, though physiological evidence of their innervation is scanty. The most popular hypothesis is that they can be stimulated by hypoxia to release mediators or to induce reflex activity. In the healthy animal, the amine-cells may control local ventilation/perfusion (V/Q) ratios via an action on the pulmonary vasculature. In disease, they may cause pulmonary hypertension. They can also give rise to three forms of tumour. Their full significance has yet to be established.

A preparation for the study of secretory function of the human bronchus in vitro.

Bronchi, not involved in tumor, were removed from resected human lungs. They were mounted in Ussing chambers containing Krebs-Henseleit solution with radiolabelled precursors of mucus. Airway was examined by both light and electron microscopy. Tissues recently removed from resected lungs exhibited both intra- and extra-cellular oedema and hypoxic changes in mitochondria, but tight junctions between epithelial cells appeared intact, indicating an effective epithelial barrier. Tissues removed from Ussing chambers after up to 6 h showed little oedema and their mitochondria were normal. Their appearance had returned to that of specimens taken that biopsy and fixed immediately. Autoradiographs of specimens from Ussing chambers showed that the mucus-producing cells had concentrated the radiolabels . Mucus in gland ducts was also radiolabelled. Damaged areas of mucous membrane were rare and probably pre-operative. We conclude that resected bronchi, suspended in Ussing chambers, have a structure and secretory activity suitable for investigations of the control of secretion.

The aminergic innervation of the human bronchus: a light and electron microscopic study.

Portions of bronchial wall, free of neoplasm, were obtained from human lung resected for nearby tumour. The bronchial tissue was freeze dried, fixed in formaldehyde vapour and sections examined by fluorescence microscopy. Wispy green fibres with the appearance of amine-containing nerves were seen associated with the gland acini. Fluorescent cells were also found at this location and infrequently in the epithelium. Fluorescence was blocked by pretreatment of the sections with sodium borohydride; it faded in ultraviolet light and was enhanced by incubation of the tissue with L-dopa. All these features are characteristic of specific formaldehyde-induced fluorescence of biogenic amines. Fluorescent fibres were not identified either in the smooth muscle of the airway or associated with the epithelium, although background fluorescence may have masked them at these sites. Observations by electron microscopy of human bronchial wall showed that, close to gland acini, there were nerves containing large dense-cored vesicles suggesting that they were sympathetic. After incubation of the tissue with 5-hydroxydopamine, nerves containing labelled vesicles were seen as close as 1 micron to the gland acini, though none were seen to run between the acinar cells. It is argued that these were sympathetic nerves and were close enough to the gland acini to influence their secretions. Nerves containing vesicles labelled with 5-hydroxydopamine were also seen in close association with smooth muscle cells indicating a direct sympathetic innervation of the bronchial smooth muscle. These observations are contrary to recent suggestions that the sympathetic nervous system acts only indirectly in the lungs.

The innervation of the trachea and extrapulmonary bronchi of the mouse.

In the mouse, nerves were located throughout the trachea and extrapulmonary bronchi in both the smooth muscle and the connective tissue. However, no nerves were found within the epithelium. In the smooth muscle there were large numbers of nonmyelinated nerves. These were usually 'en passant' elements but varicosities containing small mitochondria and vesicles were also seen; these axons sometimes appeared to be efferent to the muscle. Unilateral cervical vagotomy reduced the numbers of nerves in the muscle of the trachea and ipsilateral primary bronchus, suggesting that they were afferent. The intramuscular nerves were characterized in terms of their complement of cytoplasmic organelles; in particular nerves containing many mitochondria disappeared following vagotomy. Pretreatment of mice with 5-hydroxydopamine to accentuate the electron-opacity of catecholamine-containing granules resulted in 3.5% of the nerves within tracheal muscle showing such granules. The afferent nerves of the smooth muscle may be complex branching structures with many varicosities. The absence of epithelial nerves may be related to the absence of the cough reflex in the mouse.

Sympathomimetic drugs stimulate the output of secretory glycoproteins from human bronchi in vitro.

1. We describe a method for supporting pieces of human bronchi in Ussing chambers, for radiolabelling the contents of the secretory cells with 35S, and for collecting radiolabelled macromolecules secreted on to the luminal aspect of the tissue. This method has previously been used to study airway secretions in animals [R. J. Phipps, J. A. Nadel & B. Davis, American Review of Respiratory Disease, (1980) 121, 359-365]. Evidence is given that the radiolabelled molecules are secretory glycoproteins, probably mucus glycoproteins. 2. Phenylephrine, an alpha-adrenoceptor agonist, increased the rate at which the bronchi secreted radiolabelled glycoproteins. Thymoxamine, an alpha-adrenoceptor antagonist, blocked this effect but propranolol, a beta-adrenoceptor antagonist, did not. 3. Dobutamine, a beta-adrenoceptor agonist, increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this but thymoxamine did not. 4. Salbutamol, a beta 2-adrenoceptor agonist, also increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this effect. 5. We conclude that both alpha- and beta- adrenoceptor agonists increase the rate of glycoprotein secretion in human bronchi in vitro and that this almost certainly means that they increase the rate of mucus secretion.

The Clara cell.

The Clara cells are a group of cells, sometimes called "nonciliated bronchiolar secretory cells", found in the bronchiolar epithelium of mammals including man, and in the upper airways of some species such as mice. Their secretory function is assumed from their ultrastructural appearance, that usually includes copious smooth endoplasmic reticulum, many apical mitochondria and scanty secretory-like dense vesicles near the luminal membrane. An apical cap of the cell usually bulges into the airway lumen, and secretion may be by shedding this cap, or by diffusion secretion or by merocrine secretion in individual granules. The chemical nature of the secretion probably includes protein, glycoprotein and lipids. The secretion may contain enzymes. Its function is presumably to determine the chemical and physical properties of the lining of small airways, and it could behave as a kind of bronchiolar surfactant, limiting lung collapse. The Clara cells also contain much cytochrome P450 dependent mixed-function oxidases, which presumably play a detoxifying role. It is not known whether these oxidases can be secreted or whether they have a lipid-synthesizing function. Clara cells may be important in human disease, both by giving rise to tumours and by taking part in metaplastic changes in bronchiolar disease.

Arterial chemoreceptor-like activity in the abdominal vagus of the rat.

1. Centripetal activity in fibres in the ventral abdominal vagus nerve of the rat has been studied by recording from fine strands of the divided nerve within the abdomen. 2. In the starved animal, few spontaneously active fibres were located. A proportion of these, however, showed changes in activity in response to changes in F1 oxygen which were typical of arterial chemoreceptor afferent nerves. The resting discharge in these preparations was 0.8-8.0 impulses/sec. In response to extreme hypoxic hypoxia, histotoxic hypoxia or acetylcholine, this discharge increased markedly, with a maximum mean activity of up to 25 impulses/sec. 3. Both the mean/S.D. ratio and statistical comparison with a 'noise' equation were used to assess the apparent random nature of the spike intervals. The former indicated that the spike intervals were random but the latter test was inconclusive. 4. We suggest that this chemoreceptor-like activity originates from the abdominal vagal paraganglia and that these structures may be part of a more generally distributed chemoreceptor system.