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Biomedical subjects

R F Slocombe

Publications and source records attributed to R F Slocombe.

At least 73 records · Page 4Linked to original sources

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.

Animals↗

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.

Airway Obstruction↗

Airway responses to aerosolized methacholine and citric acid in ponies with recurrent airway obstruction (heaves).

We measured lung function and airway reactivity in response to methacholine and citric acid administered by aerosol in 2 groups of ponies (principal and control). Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction. Control ponies had no history of respiratory disease. Both principal and control ponies were paired (principal and control), and measurements were made when principal ponies were in clinical remission (Period A), following barn exposure when principal ponies had acute airway obstruction (Period B), and 1 and 2 wk after they were returned to pasture (Periods C and D). Differences between groups were primarily found at Period B. Barn housing (Period B) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) of principal but not of control ponies. When compared with control ponies at Period B, principal ponies demonstrated airway hyperreactivity. The dose of methacholine required to reduce Cdyn to 65% of baseline (ED65Cdyn) was lower, the change in RL induced by an aerosol of 0.1 mg/ml methacholine (delta RL 0.1) was higher, and the percent change in Cdyn in response to an aerosol of 0.1 mg/ml methacholine (delta %Cdyn 0.1) was larger in principal than in control ponies. A 10-min inhalation of 10% citric acid aerosol did not cause changes in Cdyn in either group of ponies. Control ponies did not increase RL in response to citric acid, whereas at Period B, RL of principal ponies increased following citric acid. We conclude that ponies in clinical remission from heaves are not hyperreactive to aerosols of methacholine or citric acid. Hyperreactivity only exists during acute exacerbations of airway obstruction.

Aerosols↗

Hemodynamic effects of acute pneumonia experimentally induced in newborn calves inoculated with Pasteurella haemolytica.

Hemodynamic responses to acute pneumonia and to hypoxia were investigated in 10 newborn calves. Experiments were performed on heparinized, anesthesized and ventilated calves. Control calves were inoculated intratracheally with bovine fetal serum. Pneumonia was induced in treated calves by intratracheal inoculation with P haemolytica suspended in bovine fetal serum. Before inoculation (base line), at the time of inoculation (T = 0), and at 30-minute intervals for 3 hours, pulmonary arterial pressure (Ppa), systemic arterial pressure, cardiac output (CO), arterial blood gases, pulmonary vascular resistance (PVR), and systemic vascular resistance were determined. At T = 0, calves in both groups became hypoxemic, alveolar-arterial O2 difference, PVR, and Ppa increased, and CO and systemic vascular resistance remained unchanged. At subsequent measurement intervals, all values returned to base-line in control calves, whereas treated calves had progressive hypoxemia associated with a decrease in Ppa and PVR, with no change in CO. Three hours after inoculation and after inhalation of 10% O2 in N2, PVR increased significantly in the control calves. In the treated group, hypoxia did not increase the resistance, compared with base-line and 3-hour values. The data indicate decreased Ppa during pneumonic pasteurellosis is because of a decrease in PVR and that pneumonia may attenuate the normal pulmonary hypoxic vasoconstrictor response.

Animals↗

Neutrophil depletion of calves with hydroxyurea: methods and clinical and pathologic effects.

Twenty-six Holstein calves were treated with hydroxyurea in order to induce neutropenia. Calves were given a daily dosage of hydroxyurea (70 mg/kg of body weight) for 4 consecutive days, and clinical signs, blood leukograms, hemograms, and platelet counts were monitored daily until the calves became neutropenic. Once a neutropenic state was induced, the calves were anesthetized and pulmonary function tests were performed. Subsequently, calves were euthanatized and complete necropsies were performed. Hydroxyurea treatment induced profound neutropenia in all calves by 8 days after initiating treatment, with mild decreases in circulating numbers of lymphocytes. Treatment did not cause clinical or pulmonary functional abnormalities. Severe pathologic changes were restricted to the bone marrow and consisted of partial to complete destruction of myeloid elements, with less severe effects on erythrocytic precursors and megakaryocytes. Hydroxyurea was useful for the induction of neutropenic states in calves and did not induce major toxic effects on other cells when given at 70 mg/kg.

Agranulocytosis↗

Comparison of three feeding techniques after esophageal mucosal resection and anastomosis in the horse.

The effects of 3 feeding techniques on healing of a cervical esophageal mucosal resection and anastomosis were investigated in 16 horses. Horses were fed a moistened pelleted diet 1 of 3 ways: 1) per os (n = 5), 2) by nasogastric (n = 5) or 3) by esophagostomy tube (n = 6) until the 14th postoperative day. The pelleted diet was then fed orally in all horses until euthanasia on the 60th postoperative day. Immediate postoperative feeding per os was unsatisfactory, as only 2 of 5 horses survived in this group. Endoscopic evaluation revealed that mucosal dehiscence of varying degrees occurred, with subsequent stricture formation in all horses. Although the incidence of some complications (fistula, sinus tract and traction diverticulum) was higher in the nasogastric tube-fed horses, 2 of 6 horses in the esophagostomy tube-fed group did not survive to the end of the study. There was more cervical phlegmon in the esophagostomy tube-fed group, and this resulted in increased periesophageal fibrosis on histopathologic examination. Radiographic measurements showed that esophageal lumen diameter increased predominantly between 30 and 45 days postoperatively. The mucosal healing time was significantly faster (p = 0.05) in the esophagostomy tube-fed group.

Animals↗

Effect of laryngeal hemiplegia and laryngoplasty on airway flow mechanics in exercising horses.

The effect of left laryngeal hemiplegia on airway flow mechanics in 5 exercising horses was examined, and the efficacy of surgical repair by prosthetic laryngoplasty was evaluated. Measurements of the upper airway flow mechanics were made with horses on a treadmill (incline 6.38 degrees) while standing (period A); walking at 1.3 m/s (period B); trotting at 2.6 m/s (period C); trotting at 4.3 m/s (period D); and standing after exercise (period E). Experiments were done on healthy horses before any surgical manipulation (control), at 10 days after left recurrent laryngeal neurectomy, and at least 14 days after prosthetic larynogoplasty. Increasing treadmill speed from period A to period D progressively increased heart rate, respiratory frequency, peak inspiratory flow, and peak expiratory flow, but inspiratory resistance and expiratory resistance remained unchanged. Neither left recurrent laryngeal neutrectomy nor prosthetic laryngoplasty affected heart rate, respiratory frequency, peak expiratory flow, or expiratory resistance when compared with those values at the control measurement periods. Left recurrent laryngeal neurectomy resulted in inspiratory flow limitation at peak inspiratory flow of approximately 25 L/s, and increased inspiratory resistance at periods D and E. Subsequent prosthetic laryngoplasty alleviated the flow limitation and reduced inspiratory resistance at measurement periods D and E.

Animals↗

Fiberoptic gastroduodenoscopy in the horse.

A method of fiberoptic gastroduodenoscopy and biopsy was developed for use in large horses. A 275 cm X 13.5 mm fiberendoscope was used to examine the stomach and proximal portion of the duodenum. Food was withheld for 24 to 48 hours before examination. In more than 50 horses, gastric and duodenal structures were easily visualized. A variety of lesions was detected, including parasitic lesions, gastric ulcers, gastric neoplasia, and pyloric stenosis. Mucosal biopsy specimens were obtained in selected cases.

Animals↗

Airway reactivity in ponies with recurrent airway obstruction (heaves).

We measured lung function and airway reactivity to histamine administered by aerosol in two groups of ponies. Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction when ponies are housed in a barn and fed hay; control ponies had no history of airway obstruction. Ponies were paired (principal and control) and measurements were made when principal ponies were at pasture and in clinical remission (period A), following barn housing when principal ponies had acute airway obstruction (period B), and after a further 1 and 2 wk at pasture (periods C and D). At periods A, C, and D dynamic compliance (Cdyn), pulmonary resistance (RL), arterial O2 tension (PaO2), and CO2 tension (PaCO2) of principals and controls did not differ. Barn housing (period B) decreased Cdyn and PaO2 and increased RL in principals but not controls. The ED65Cdyn (the dose of histamine to reduce Cdyn to 65% of base line) did not differ in principals and controls at periods A, C, and D. At period B, ED65Cdyn decreased by 2.5-log doses of histamine in principals while ED65Cdyn was not affected in controls. There was no correlation between changes in airway reactivity and changes in RL and Cdyn. We conclude that ponies in clinical remission from heaves are not hyperreactive to histamine aerosol. This model of lung disease is similar to some forms of industrial asthma in which hyperreactivity occurs only during acute airway obstruction. The lack of correlation between ED65Cdyn and the degree of airway obstruction suggests that the hyperreactivity of principal ponies to histamine aerosol cannot be explained solely by alterations in baseline airway caliber.

Animals↗

Bronchoalveolar lavage in ponies with recurrent airway obstruction (heaves).

We performed bronchoalveolar lavage (BAL) in 2 groups of ponies. Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction and airway hyperreactivity when ponies are housed in a barn and fed hay; control ponies had no history of airway obstruction. Ponies were paired (principal and control), and BAL was performed after 2 months of being pastured when principal ponies were in clinical remission (Period A), after barn housing when principal ponies had acute airway obstruction (Period B), and after a 1- and a 2-wk recovery phase of pasture grazing (Periods C and D). At Periods A, C, and D, white blood cell counts and immunoglobulin/albumin ratios in peripheral blood and BAL fluid of principal and control animals did not differ. Peripheral blood white cell counts and immunoglobulin/albumin ratios were unaffected by barn exposure and return to pasture. However, at Period B, neutrophil numbers in the BAL fluid were increased in the principal but not in the control animals. The IgG/albumin ratio of the principal animals increased at Period C. We conclude that in ponies with a history of heaves, barn exposure results in increased neutrophils in BAL fluid. In this pony model of lung disease, pulmonary leukostasis follows a time course similar to that of airway obstruction and airway hyperreactivity.

Albumins↗

Intravenous histamine administration in ponies with recurrent airway obstruction (heaves).

Pulmonary function and airway reactivity to IV histamine were measured in a group of ponies with a history of recurrent airway obstruction (heaves) and their age-, weight-, and gender-matched controls. Ponies were studied during a period of clinical remission (period A), after exposure to a barn environment (period B), and twice during a 2-week recovery phase (periods C and D). At periods A, C, and D, PaO2, dynamic compliance (Cdyn), pulmonary resistance, tidal volume, respiratory frequency, and the log dose of histamine required to reduce Cdyn to 65% of base-line value (log ED65Cdyn) of principals and controls did not differ. Barn exposure (period B) decreased Cdyn, PaO2, and ED65Cdyn and increased pulmonary resistance in principals but not controls. The slope of the histamine dose-Cdyn response curves was not different between principal and control groups of ponies and was unaffected by barn exposure or return to pasture. There was a poor correlation between ED65Cdyn and indices of airway caliber. During acute airway obstruction, ponies with a history of heaves were hyperreactive to IV histamine, but during disease remission, airway response to histamine was not different from that of control ponies. Seemingly, hyperreactivity in principal ponies after exposure to a barn environment cannot be explained solely by alterations in base-line airway caliber.

Airway Obstruction↗

Importance of neutrophils in the pathogenesis of acute pneumonic pasteurellosis in calves.

Acute lung injury was induced in 24 calves by intratracheal inoculation with Pasteurella haemolytica. Calves in groups 1 and 2 were neutrophil depleted, using hydroxyurea given IV. Group 1 calves (n = 7) were inoculated intratracheally with saline solution, and group 2 calves (n = 7) were inoculated with P haemolytica. Group 3 calves (n = 7) had normal numbers of neutrophils and were inoculated with P haemolytica. Group 4 calves (n = 3) were treated acutely with hydroxyurea IV, had normal numbers of neutrophils, and were inoculated with P haemolytica. After inoculation, calves with normal numbers of neutrophils (groups 3 and 4) became hypoxemic 2 hours after inoculation, and hypoxemia persisted until necropsy (6 hours after inoculation). These calves also developed tachypnea, bradycardia, neutropenia, and lymphopenia. Lung lesions consisted of necrosis of the alveolar walls, intra-alveolar hemorrhage, and a severe exudative and necrotizing bronchopneumonia, with accumulation of proteinaceous fluid in alveoli and lymphatics. In neutrophil-depleted calves (groups 1 and 2), blood gas values, heart and respiratory rates, and numbers of circulating leukocytes did not change after inoculation with saline solution or with P haemolytica. At necropsy, the lungs of neutrophil-depleted calves were grossly normal. Therefore, neutrophils were required for the acute lung injury induced by P haemolytica. The protective effect of neutrophil depletion was a specific effect of hydroxyurea because calves with high circulating concentrations of hydroxyurea and calves with normal numbers of neutrophils (group 4) developed lung injury.

Acute Disease↗

Regional interdependence in calf lungs.

We measured K, an index of interdependence in sublobar segments of both intact and excised calf lungs. In excised and intact lungs, segment volume was held constant while the lung was inflated. K in excised lungs was of small magnitude but was greater in caudal than in cranial and middle lobes. When isolated segments in a variety of regions and with a variety of shapes were studied, K was positively correlated with the interface area between the segment and the remainder of the lung, was negatively correlated with the pleural surface area of the segment, but was not correlated with segment volume. In a given region of lung, however, small segments had a greater interdependence than large segments. In intact lungs of anesthetized calves, K was an order of magnitude greater than in excised lungs, confirming that the chest wall is the major determinant of interdependence. There were no lobar differences in K in intact lungs.

Anesthesia, General↗

Interactions of cold stress and Pasteurella haemolytica in the pathogenesis of pneumonic pasteurellosis in calves: method of induction and hematologic and pathologic changes.

Six healthy neonatal calves were chilled with cold water and had focal tracheitis induced by spraying 5% acetic acid into the tracheal lumen. Subsequently, 20 ml of sterile saline solution was injected intratracheally. The effects of these interventions on total and differential white cell counts, plasma cortisol, histamine, and bradykinin, hematocrit, total plasma solids, and indices of the erythrocyte size and hemoglobin content were determined over the subsequent 12 hours. Cold stress increased plasma cortisol levels for less than 1 hour, but did not alter any other variable. This group of calves served as a control group for a second series of neonatal calves which were given 2 X 10(9) organisms of Pasteurella haemolytica intratracheally immediately following an identical period of chilling and acetic acid exposure. Calves given P haemolytica became neutropenic. There were increased numbers of circulating band neutrophils by 12 hours after exposure, and serum cortisol values were maintained at the same or greater than cold stress concentrations for all measurement periods subsequent to exposure. Infected calves had acute fibrinous pneumonia from which P haemolytica was isolated. Contrary to previous reports, these data may indicate a role for the neutrophil in the pathogenesis of early lesions of pasteurellosis. Although the association of circulating corticosteroids with stress and subsequent infection is clear, our data provide no evidence to indicate that circulating histamine or bradykinin are involved in the pathogenesis of the acute lesions of Pasteurella pneumonia.

Animals↗

Interactions of cold stress and Pasteurella haemolytica in the pathogenesis of pneumonic pasteurellosis in calves: changes in pulmonary function.

Thirteen healthy neonatal Holstein calves were cold stressed twice by hosing with cold water for 20 minutes, 12 hours between hosings. Measurements of the pattern of ventilation [tidal volume (VT), respiratory frequency (f), minute ventilation (VMIN), and functional residual capacity (FRC)], gas exchange properties of the lungs [alveolar ventilation (VA), oxygen uptake (VO2), CO2 production (VCO2), dead space ventilation (VD), dead space/tidal volume ratio (VD/VT), arterial oxygen tension (PaO2), arterial CO2 tension (PaCO2) and alveolar-arterial oxygen difference (AaDO2)] and of the mechanical properties of the pulmonary system [dynamic compliance (Cdyn), pulmonary resistance (RL), and total respiratory system resistance (RRS)] were taken. Calves responded to chilling by increasing VO2 and VCO2 necessitating an increase in VA. This was accomplished by increasing VT with reciprocal decreases in f so that VMIN remained constant. There was no change in Cdyn, RL, or AaDO2. Seven of these 13 calves were then exposed to intratracheal inoculation of 2 X 10(9) organisms of Pasteurella haemolytica, the remaining calves serving as controls. Within 1 hour, calves exposed to P haemolytica had increased VMIN, f, VD/VT, and VD. There was a decrease in PaO2 associated with increased AaDO2, but no change in PaCO2, Cdyn or RL. By 3 hours after inoculation, there were pronounced changes in PaO2 and AaDO2, and Cdyn was reduced below base-line values. By 12 hours after inoculation, calves infected with P haemolytica had increased RL and RRS and PaCO2, in addition to the previously mentioned changes. Data from Pasteurella-exposed calves indicate that gas exchange impairment and peripheral lung injury occur rapidly and that increases in airway resistance develop relatively late in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Esophagotomy in the pony: comparison of surgical techniques and form of feed.

Esophageal healing was studied in 12 ponies after cervical esophagotomy. The esophagus was sutured, feed and water were withheld for 48 hours, and then all ponies were permitted to eat. In group I (n = 6), a longitudinal esophagotomy was made. In group II (n = 6), a rotational esophagotomy was made with the mucosal incision 180 degrees away from the incision in the esophageal muscle. Three ponies in each group were fed a soft diet ad libitum for 9 days, and then were allowed access to hay and grain. The remaining ponies were fed hay and grain. The esophagotomies of all hay-fed ponies dehisced and healed by second intention, whereas esophagotomies healed by first intention in the ponies given a soft diet. Endoscopic and radiographic examinations indicated that the progression of healing in the present study was a function of diet (form of food), rather than surgical technique. The cross-sectional width of the muscularis externa at the incision site was 39.6% greater in mash-fed ponies than in hay-fed ponies. Based on density-dependent image analysis, average elastin content and reticulin fiber of the submucosa and muscularis externa at the incision were not influenced by the form of feed or surgical technique, although elastin fiber regeneration did not occur at the site of the incision.

Animal Feed↗