Effect of Pasteurella haemolytica-derived endotoxin on pulmonary structure and function in calves

The role of endotoxin in the pathogenesis of acute pneumonic pasteurellosis is uncertain. Recently, we reported that Escherichia coli-derived endotoxin given by airway inoculation fails to induce lung injury in calves. Because Pasteurella haemolytica-derived endotoxin may differ substantially from E coli in its pathogenicity, we repeated these studies with Pasteurella endotoxin. Intratracheal inoculation of P haemolytica endotoxin caused hypoxemia and increased the alveolar-arterial oxygen differences without causing hypercarbia or changes in lung mechanical properties and volumes. In contrast, IV inoculation of endotoxin caused systemic hypotension, leukopenia, gas exchange impairment, increased total pulmonary resistance, and decreased dynamic compliance. Both routes of inoculation increased serum endotoxin concentrations and were associated with areas of pulmonary hemorrhage, edema, and acute inflammation. We concluded that P haemolytica-derived endotoxin is pathogenic by IV and airway routes of inoculation, and therefore differs from E coli endotoxin in its ability to induce lung lesions in calves.     

Histamine H1, H2 receptor effects on mechanics of ventilation and gas exchange in neonatal calves

The effect of histamine infusion (IV) on pulmonary mechanical and gas exchange properties of healthy neonatal Holstein-Friesian calves was determined. Histamine increased pulmonary resistance and static pressure-volume hysteresis and decreased dynamic compliance, but failed to change static compliance; changes were compatible with constriction of both large and small airways without a change in lung elasticity. Histamine decreased arterial oxygen tension by increasing the alveolar-arterial oxygen difference, probably because ventilation-perfusion inequalities resulted from small airway constriction. The pulmonary mechanical and gas exchange effects of histamine were prevented by pretreatment with the H1 receptor antagonist, tripelennamine, but not with the H2 receptor antagonist, metiamide. The histamine-induced changes in static pressure-volume hysteresis and dynamic compliance were reversed by sighing, and histamine effects on the lung were eliminated by 15 minutes after cessation of histamine infusion.     

Effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange in endotoxemic pigs

The effects of ketanserin on pulmonary hemodynamics, lung mechanics, and gas exchange were determined in anesthetized 10- to 14-week-old pigs after they were endotoxemic for 1 or 4.5 hours. Saline solution was given to controls (group 1). Escherichia coli endotoxin (055-B5) was infused IV at a dosage of 5 micrograms/kg for 1 hour (group 2). In group 3, endotoxin was infused at 5 micrograms/kg the first hour plus a continuous infusion of endotoxin at 2 micrograms/kg/hr. Ketanserin, a specific serotonin receptor antagonist, was infused IV (300 micrograms/kg) after pigs were endotoxemic for 1 or 4.5 hours (groups 2 and 3, respectively). At 1 hour of endotoxemia, mean pulmonary artery pressure and pulmonary vascular resistance were increased, and cardiac index was decreased. Ketanserin caused a small attenuation of the increases in mean pulmonary artery pressure and pulmonary vascular resistance, indicating that serotonin may have a small role in the endotoxin response at 1 hour. At 4.5 hours of endotoxemia, mean pulmonary artery pressure, pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen gradient were increased, and cardiac index and lung dynamic compliance were decreased; ketanserin significantly attenuated the endotoxin-induced changes in cardiac index, mean pulmonary artery pressure, pulmonary vascular resistance, and lung dynamic compliance. Ketanserin also decreased the blood temperature after pigs were endotoxemic for 4.5 hours. However, the endotoxin-induced increases (at 4.5 hours) in alveolar-arterial oxygen gradient and alveolar dead space ventilation were not acutely reversed by ketanserin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intravenous and aerosol administration of 5-hydroxytryptamine on pulmonary function values in healthy calves.

Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous IV administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5-HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction.     

Dexamethasone-induced attenuation of cardiopulmonary dysfunction in endotoxemic calves

Effects of dexamethasone on pulmonary hemodynamics, pulmonary mechanics, and gas exchange were determined in anesthetized (pentobarbital sodium) and paralyzed (pancuronium bromide) calves (9.4 +/- 0.4 weeks old) during 5 hours of endotoxemia. Escherichia coli endotoxin (055-B5) was infused IV at 20 micrograms/kg the 1st hour, followed by a continuous infusion at 10 micrograms/kg/hour for the following 4 hours. Dexamethasone (5 mg/kg) was given IV 18 hours and 1 hour before endotoxin administration, and was also administered IV (1 mg/kg/hr) during endotoxemia. Endotoxin induced large increases in pulmonary artery pressure, pulmonary vascular resistance, alveolar-arterial O2 gradient, alveolar dead-space ventilation, postmortem gravimetric lung weight of bloodless lung, albumin and total protein concentrations in bronchoalveolar lavage fluid, and the number of neutrophils recovered from bronchoalveolar lavage fluid. Endotoxin induced decreases in the cardiac index, dynamic lung compliance, and PaO2. Dexamethasone attenuated most of the cardiopulmonary responses induced by endotoxin, especially during the first 3 hours of endotoxemia. Dexamethasone blocked endotoxin-induced increases in bronchoalveolar lavage albumin, total protein, and neutrophil content. Therefore, glucocorticoids modify endotoxin-induced pulmonary injury in calves, possibly by limiting mobilization of endogenous arachidonic acid.     

BW755C modifies endotoxin-induced respiratory failure in pigs

The porcine pulmonary response to endotoxemia was evaluated before and after 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C), a dual inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Escherichia coli endotoxin (055-B5) was infused IV into anesthetized 10- to 14-week-old pigs at 5 micrograms/kg the first hour, followed by 2 micrograms/kg/hr for 3.5 hours. The BW755C was infused at 20 mg/kg before endotoxin was administered and at 2.2 mg/kg during endotoxemia. During phase 1 (ie, 0 to 2 hours), the endotoxin-induced pulmonary hypertension, increased pulmonary vascular resistance and alveolar-arterial oxygen gradient, and decreased cardiac index and lung dynamic compliance were blocked or modified by BW755C. During phase 2 endotoxemia (ie, 2 to 4.5 hours), BW755C modified or blocked the increases in pulmonary vascular pressures, pulmonary vascular resistance, alveolar dead space ventilation, alveolar-arterial oxygen gradient, lung water, and bronchoalveolar lavage albumin concentration. The BW755C also modified the phase 2 decreases in cardiac index, lung dynamic compliance, and aortic platelet count. With regard to the endotoxin-induced pulmonary vasoconstriction, bronchoconstriction, and impairment of gas exchange, the data do not support a role for lipoxygenase metabolites, because the modified blockade (provided by BW755C) was of no greater magnitude than that reported for indomethacin (cyclooxygenase blocker). However, the data supports a possible role for lipoxygenase metabolites with regard to altering vascular permeability, cardiac index, and aortic platelet count.     

LUNG LOBE COLLAPSE

The radiographic changes caused by collapse of lung lobes in pulmonary disease, pneumothorax, and pleural effusion depend on the lobar recoiling force and local pleural pressure. Differences in the tendency of normal lung lobes or regions to collapse depend on the relative surface-to-volume ratio, determined by shape and size of the region or lobe. This ratio affects the physiologic parameters of pulmonary interdependence, compliance, and collateral air flow. Pulmonary surfactant increases compliance, particularly at low volumes, maintains alveolar stability, and assists in maintaining capillary patency and preventing pulmonary edema. Its loss due to lung injury increases collapsing forces. In the presence of pneumothorax or pleural effusion, diseases that cause lobar collapse produce localized air or fluid entrapment that is a diagnostic sign of the presence of the underlying pulmonary disease.     

Respiratory mechanics in Standardbred horses with sub-clinical inflammatory airway disease and poor athletic performance

The aim of this study was to investigate and quantify respiratory mechanical dysfunctions in Standardbred horses with both poor performance and bronchoalveolar lavage fluid cytology characteristic of inflammatory airway disease (IAD). A control group of healthy Standardbred horses was compared. Respiratory mechanics and breathing pattern were examined at rest and during hyperventilation induced using a rebreathing method. At rest, respiratory mechanics and breathing pattern were superimposable in both groups. In IAD horses, rebreathing increased ventilation, with larger tidal volumes and lower respiratory frequencies. During hyperventilation, IAD animals showed frequency-dependent dynamic lung compliance, and had greater viscous lung resistance and rate of dynamic work of breathing. As IAD alters pulmonary mechanics, the ventilatory load increases and horses requiring significantly higher energy for breathing may suffer restrictions in their athletic performance. This rebreathing method permits early evaluation of respiratory mechanical dysfunction in poorly performing horses with sub-clinical IAD.     

Effects of general anaesthesia on static respiratory compliance in dogs

The effect of anaesthesia on total, pulmonary and chest wall static respiratory compliance was investigated in healthy spontaneously breathing dogs undergoing orthopaedic surgery. Total compliance fell by 26 per cent from the baseline measurement within 25 minutes of the first measurement (P less than 0.01), while pulmonary and chest wall compliances fell by 34 per cent and 40 per cent, respectively (P less than 0.01). Pulmonary compliance ceased to fall after 50 minutes, but chest wall compliance was still declining after 70 minutes. The decline in compliance could be prevented by periodic full lung inflation, with a significant difference being found between inflated and uninflated dogs (P less than 0.01). The reduction in compliance during anaesthesia is believed to be a consequence of reduced functional residual capacity and the development of lung tissue atelectasis.     

Longitudinal study of the effects of lungworm infection on bovine pulmonary function

Clinical and physiologic investigations were done weekly in 5 nonsedated Friesian calves before, during, and after an induced infection with Dictyocaulus viviparus infective larvae. Clinical, hematologic, serologic, and parasitologic findings were all compatible with the classic picture of moderate subacute verminous bronchitis. Most pulmonary function values revealed significant (P less than or equal to 0.05) changes in the 2nd or 3rd week after inoculation and maximal changes at 5 weeks after inoculation. Most marked changes included a decrease in tidal volume, dynamic lung compliance, and arterial oxygen tension, and an increase in minute ventilation, minute viscous work of breathing, and alveolar-arterial oxygen difference. Minute ventilation, dynamic lung compliance, minute viscous work of breathing, and PaO2 revealed the most homogeneous change. Conversely, maximal change of intrapleural pressure, total pulmonary resistance, and viscous work of breathing had higher variability from week to week.     

Comparison of pathophysiologic changes in the lungs of calves challenge exposed with Escherichia coli-derived endotoxin and Pasteurella haemolytica, alone or in combination

Pulmonary responses to intratracheal challenge exposure with Pasteurella haemolytica, with or without Escherichia coli-derived endotoxin, E coli endotoxin alone, or saline solution were compared in anesthetized, mechanically ventilated neonatal calves. Baseline values for dynamic compliance, total pulmonary resistance, functional residual capacity, arterial blood gas tensions, hemogram, leukogram, and systemic and pulmonary arterial pressures were recorded for each calf. After baseline data were obtained, calves were challenge exposed with logarithmic-growth phase P haemolytica organisms with or without E coli endotoxin, E coli endotoxin alone, or saline solution (0.9% NaCl). Physiologic data were obtained immediately after challenge exposure and at various intervals over the next 6 hours. Calves challenge exposed with P haemolytica alone developed sever hypoxemia, had increased alveolar-arterial oxygen difference and threefold increases in total pulmonary resistance, became hypercarbic, had decreased functional residual capacity, and developed systemic hypotension without change in pulmonary arterial pressure. At necropsy, these calves had extensive multifocal areas of necrohemorrhagic and purulent pneumonia. Ratio of extravascular lung water to lung dry weight was not significantly increased in lung specimens obtained from calves challenge exposed with P haemolytica, but ratio of lung wet weight to dry weight was increased, indicating that increased lung wet weight was attributable largely to increased solids and not to fluid alone. (Extravascular lung water measurement excludes fluid from the vascular compartment.) Intratracheal challenge exposure with endotoxin failed to alter lung function and caused minor changes in lung structure consisting of focal areas of hemorrhage and edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional changes induced by necrotic laryngitis in double muscled calves

The effects of necrotic laryngitis on the mechanics of breathing and gas exchange were investigated in five Belgian blue double muscled calves two to three months old. All the animals showed the typical clinical picture of the respiratory syndrome associated with naturally occurring necrotic laryngitis. Highly significant increases in total pulmonary resistance, minute viscous work of breathing and alveolar-arterial oxygen gradient, and highly significant decreases in dynamic lung compliance and arterial oxygen tension were recorded in the infected animals, when compared to reference values for healthy cattle. The ratio of inspiratory to expiratory viscous work of breathing was also significantly increased probably because of a partial collapse of the extrathoracic trachea during inspiration. It was concluded that necrotic laryngitis disturbs pulmonary function to such an extent that it impedes the growing process and predisposes the infected animals to secondary bronchopneumonia and ventilatory failure due to respiratory muscle fatigue.     

Effects of a demand valve on pulmonary ventilation in spontaneously breathing, anaesthetised horses

The pressure flow characteristics of a demand valve which has been suggested to be suitable for use in anaesthetised horses were determined at a range of flow rates commonly encountered in equine anaesthesia. The resistance of the valve was found to be very much greater than the resistance of normal large animal anaesthetic apparatus or the equine lower respiratory tract. The effects of the valve on pulmonary ventilation were investigated in seven anaesthetised, intubated horses. Respiratory rate and dynamic compliance were unaffected by connection of the valve but mean tidal and minute volumes and peak flow rates were substantially reduced. The change in transpulmonary pressure over the respiratory cycle was doubled and indices of work of breathing increased by a factor of three. It was concluded that the resistance offered by the valve was too great for its use in spontaneously breathing horses to be recommended.     

Comparative pulmonary mechanics in the horse and the cow

Pulmonary mechanics and lung volumes were measured in horses and cows to determine if differences in breathing pattern between the two species were due to differences in the mechanical properties of the lungs. Tidal volume (VT) was larger in the horses, while the respiratory rate (fR) and minute ventilation (VE) were higher in the cows. The horses often had a double peak in airflow during inspiration and, or, expiration, while the cows had a single peak during expiration. Measured lung volumes were larger in the horses and they had a higher dynamic lung compliance (Cdyn,L), although the static compliance of the lung, chest wall and respiratory system (Cst,L,Cst,w and Cst,rs respectively) did not appear to differ between the two species. The cows had a greater change in maximum transpulmonary pressure (delta PLmax) and an increased nonelastic work of breathing (Wb). However, the pulmonary resistance (RL) did not differ between the two species, thus the higher delta PLmax and Wb in the cows were most likely a function of their higher flow rates. Calculations of the rate of work of breathing (W) indicate that both species breathed at an fR above the minimum W. The fR in the horses was close to the fR predicted for the average minimum muscle force, but the fR in the cows was higher. As the differences in the mechanical properties of the lung do not explain the differences in flow pattern, nor adequately account for the higher fR in the cows, it is suggested that the differences in breathing pattern between the two species is due to differences in the chest wall, particularly the size and shape of the abdomen.     

Effects of aerosolized histamine and carbachol in the conscious horse.

Pulmonary function tests were performed in seven conscious, standing horses. Changes in pulmonary mechanics and ventilation volumes were measured after inhalation challenge with saline (baseline), histamine (1% w/v solution for 5 min) and carbachol (0.5% w/v solution for 3 min). Comparisons between baseline and posthistamine values revealed a significant (P less than 0.05) increase in nonelastic work of breathing (Wb), maximum change in transpulmonary pressure (max delta Ppl), and pulmonary resistance (RL), while dynamic compliance (Cdyn) decreased (P less than 0.05). Tripelennamine completely abolished these histamine induced changes suggesting the involvement of H1 receptors. A nonsignificant increase occurred in functional residual capacity. However, the amount of nitrogen retained in the lung at the end of a nitrogen washout test was significantly (P less than 0.05) greater after histamine when compared to baseline values. The effect of carbachol was qualitatively similar to that of histamine, Wb and max delta Ppl increased while Cdyn decreased (P less than 0.05). The increase in lower RL reached statistical significance (P less than 0.05) only at the beginning of expiration (/ 25% VT). The present investigation demonstrates that the physiological measurements of lung function could be carried out in conscious, unsedated horses and that the pulmonary function test methods could be used as a tool for study of drug induced changes in pulmonary mechanics.     

Effects of xylazine on airway function in ponies with recurrent airway obstruction.

The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did not affect PaO2 or PaCO2. The alpha 2-antagonist yohimbine blocked the pulmonary effects of xylazine. Administration of saline solution was without effect in both groups of ponies at all periods and xylazine did not have effect in controls or in principals in clinical remission.     

Study of the effect of Bronchipret on the lung function of five Austrian saddle horses suffering recurrent airway obstruction (heaves)

The effects of an oral preparation containing an extract of thyme and primula (Bronchipret; Bionorica) on the lung function of five horses suffering heaves were determined in a longitudinal study. The horses accepted the product well. The plasma concentrations of the marker substance, thymol, indicated that at least one of the substances in the extract had been absorbed from the gastrointestinal tract. The compliance, pulmonary pressure and airway resistance of the horses' lungs were all significantly improved after one month of treatment However, the severity of their clinical signs and their arterial oxygen partial pressure had not improved significantly.     

Pulmonary dysfunction in neonatal calves after intratracheal inoculation of small volumes of fluid

Intratracheal instillation of 20 ml of room temperature (21 to 24 C) fluid in anesthetized neonatal calves resulted in rapid onset of reversible pulmonary dysfunction. Arterial O2 tension and dynamic compliance decreased, whereas pulmonary arterial pressure, pulmonary vascular resistance, alveolar arterial O2 difference, and total pulmonary resistance increased from base-line values. Abnormalities of gas exchange and pulmonary mechanics were induced by intratracheal fluid instillation whether or not Pasteurella haemolytica was in the inoculum. Physical manipulation of the calf without intratracheal fluid instillation (sham inoculation) did not influence pulmonary function. Bilateral vagotomy eliminated the increase in pulmonary resistance and the decrease in dynamic compliance, but did not eliminate hypoxemia, increased alveolar arterial O2 difference, or pulmonary hypertension recorded after intratracheal fluid instillation. Seemingly, changes in pulmonary mechanics are mediated via the vagus nerve. However, one or more additional mechanisms must be responsible for the hypoxemia and pulmonary hypertension.     

Effect of clenbuterol on histamine-induced airway obstruction in ponies

We determined the effect of IV administered beta 2-adrenergic receptor agonist clenbuterol on pulmonary function and on the response to histamine in 12 healthy ponies. Measurements were made at base line and after saline solution or clenbuterol was administered IV at a dosage of 0.2, 0.8, or 1.6 micrograms/kg. The dosage of clenbuterol used in each study was unknown to the investigators until all the data had been analyzed. Intravenous administration of saline solution or clenbuterol did not alter base-line pulmonary function significantly. Aerosol histamine administration significantly decreased arterial oxygen tension and dynamic compliance and increased pulmonary resistance, respiratory frequency, and minute ventilation, but had no effect on arterial carbon dioxide tension and tidal volume. The magnitude of change in these variables was unaffected by previous administration of clenbuterol at any of the dosages tested. We conclude that clenbuterol at the dosages tested is not a bronchodilator in healthy ponies and does not exert a significant protective effect against aerosol histamine-induced airway narrowing.     

Effects of xylazine on equine intestinal vascular resistance, motility, compliance, and oxygen consumption

Isolated jejunal segments were perfused at a constant blood flow rate to determine simultaneously the effects of xylazine on intestinal vascular resistance, motility, compliance, and oxygen consumption in 12 anesthetized ponies. Xylazine was infused into the artery perfusing the intestinal segment (group 1), or into the jugular vein as a single IV bolus (group 2), or 3 times as IV boluses repeated at 10-minute intervals (group 3). Dose-response curves in group 1 indicated a biphasic response to the drug with vasoconstriction, increased motility, and increased oxygen consumption at lower doses followed by a return toward base-line values at higher doses. Intestinal compliance decreased at lower doses, but increased at higher doses. A single IV bolus of xylazine (group 2) induced systemic hypotension for 30 minutes, and increased intestinal vascular resistance for 10 minutes accompanied by increased motility, and repeatedly administered IV boluses of xylazine (group 3) increased and prolonged these effects. The results indicated that xylazine, especially in repeated doses, may decrease bowel viability by simultaneously increasing intestinal vascular resistance, motility, and oxygen consumption.