Doctor of Philosophy / Department of Diagnostic Medicine and Pathobiology / Brad J. White and Robert L. Larson / Bovine respiratory disease (BRD) is the most costly disease of cattle in US feedyards and diagnosis based on clinical signs of illness is challenging. Over the course of five independent studies we evaluated the precision of multiple observers assigning clinical illness scores (CIS) to calves with induced Mycoplasma bovis pneumonia. We also evaluated the accuracy of CIS in relation to lung lesions at necropsy. Agreement among observers over all five studies was slight ({kappa]= 0.16; 95% confidence interval, 0.10 to 0.24) and ranged from 0.10 to 0.21 for individual trials. The accuracy of CIS varied based on the pulmonary consolidation score chosen to represent a truly ill animal. Inflammation associated with BRD can lead to significant pulmonary damage and reduced lung function. Treatment for BRD frequently involves antimicrobial administration and occasionally non-steroidal anti-inflammatory drugs. We evaluated how calves experimentally challenged with Mannheimia haemolytica respond to treatment with flunixin meglumine, alone or in combination with the antimicrobial florfenicol. Individual calf response to bacterial pneumonia was highly variable in this study. None of the changes in serum biomarkers, CBC or chemistry parameters provided reliable indicators of the pulmonary inflammation associated with the mild severity of bronchopneumonia in our study. Metaphylaxis is frequently administered to manage the risk of BRD within cohorts of cattle. We evaluated the impact of metaphylactic antimicrobial administration 10 days prior to experimental Mannheimia haemolytica inoculation to mitigate pulmonary lesions. We found that calves receiving tildipirosin had less lung damage and fewer clinical signs of illness compared to calves treated with tulathromycin or saline. Finally, the ability to predict those animals that would not finish the production cycle normally would provide benefits in effectively managing cattle. We evaluated the ability of classification algorithms to accurately predict an individual calf’s outcome based on data available at first identification of and treatment for BRD. We found accuracy of classifiers was dependent on the data recorded by the feedyard and there are sub-groups of calves within feedyard populations where classifiers were highly accurate. These data suggest the importance of pairing the proper classifier with the data available.

The objectives of this project were: 1) to determine if live animal lung biopsy could be used to characterize early pathologic changes in the bovine lung associated with bovine respiratory disease (BRD), 2) determine if specific infectious respiratory pathogens can be identified in association with early pathological changes, and 3) determine whether pulmonary pathology characterized by live animal lung biopsy at arrival and at the time of initial BRD diagnosis was associated with health and production outcomes of feedlot steers in a commercial feedlot.<p> A live animal percutaneous lung biopsy technique was developed to obtain a lung sample from the right middle lung lobe in intercostal space (ICS) 4 using a Bard® Magnum® reusable biopsy instrument and a modified 4-mm (8g) biopsy needle. The lung biopsy procedure was limited to 2 attempts per biopsy time. In the technique development, 34 animals chronically affected with BRD were utilized, 20 animals in the preliminary development followed by 14 additional animals in a commercial feedlot setting. The technique resulted in 1 fatality of 34 steers (2.9%) and lung parenchyma was harvested in 19 of 34 steers (55.9%) chronically affected with BRD. In addition, in the commercial feedlot setting this procedure was determined to take about 20 minutes per animal.<p> The final study was performed on one hundred feedlot steers considered at high risk of developing BRD from twenty pens within a commercial feedlot. Study animals were enrolled in three different groups: sick on arrival (ARR-SA) consisting of 27 study animals and 13 matched control animals; pen pulls with no fever (PP-NF) consisting of 14 study animals and matched 7 controls; and pen pulls with an undifferentiated fever (PP-UF) consisting of 26 study animals and 13 matched controls. Live animal percutaneous lung biopsies were collected from the right middle lung lobe at 3 different times within the first 30 days of the feeding period, about 2 weeks apart. All samples were histopathologically evaluated and were assessed for the presence of <i>Mycoplasma bovis</i>, <i>Mannheimia haemolytica</i>, Histophilus somni and bovine viral diarrhea virus with immunohistochemistry.<p> A total of 295 lung biopsies were performed yielding 210 (71.2%) lung samples that were sufficient for histopathological evaluation. A histopathology score was awarded to each biopsy based on certain histopathological lesions being present. Only 20 lung biopsy samples from 19 animals received a histopathology score (ie, pulmonary lesions were present) with the most common score being a 1 (maximum score is 20). There were too few lung biopsy samples with a histopathology score to reveal any association with subsequent health events.<p> Immunohistochemistry (IHC) was performed on all lung biopsies recovered yielding one lung sample to be positive for both <i>Mannheimia haemolytica</i> and <i>Mycoplasma bovis</i> from the PP-UF group. There were too few positive samples to reveal any association between IHC and histopathology score.<p> A post mortem evaluation was performed by a study veterinarian on all study animals who died or were humanely euthanized due to poor treatment response. In this study only 4 steers died or were euthanized due to poor treatment response and 3 control steers were humanely euthanized. There were too few animals to reveal any association between histopathology score and post mortem diagnosis.<p> On entry into the feedlot, weights between ARR-SA and the PP-UF and PP-NF groups were significantly different (p<0.05). This is likely an effect of the different processing groups of cattle. At study allocation, the body weights of ARR-SA and PP-UF, PP-UF and their matched controls, and PP-NF and their matched controls were also significantly different (p<0.05). This is likely due to the PP-UF and PP-NF groups experiencing illness for a longer period of time resulting in greater weight loss than the ARR-SA animals as well as the control animals, who were not clinically sick.<p> The live lung biopsy procedure utilized in this study did not appear to cause any long lasting adverse effects as the BRD case fatality rates from the study animals were comparable to the overall case fatality rates reported by the feedlot for fall placed calves. In fact, the study animals experienced a decreased fatality rate compared to the feedlots overall fatality rate. This may be due to the study animals inadvertently being monitored more closely as the pen checkers were aware of and participating in the study. On post mortem evaluation there was no evidence of adhesions at the biopsy site. This procedure was performed on 134 feedlot steers resulting in only 2 acute deaths as a direct result of the live animal percutaneous lung biopsy procedure.<p> The results of this study indicate that live animal, percutaneous lung biopsy can be performed safely on feedlot steers in a commercial feedlot with few clinical side effects. In this study there were only 2 fatalities in 134 steers (1.5%) due to the biopsy procedure or 2 fatalities per 349 sampling times (0.6%) This technique did not prove useful either as a diagnostic tool for the determination of early lung pathology in BRD or as prognostic indicator for health and production outcomes. However, this lung biopsy technique may be a useful diagnostic tool for chronic pneumonia assessment.

The objectives of this project were: 1) to determine if live animal lung biopsy could be used to characterize early pathologic changes in the bovine lung associated with bovine respiratory disease (BRD), 2) determine if specific infectious respiratory pathogens can be identified in association with early pathological changes, and 3) determine whether pulmonary pathology characterized by live animal lung biopsy at arrival and at the time of initial BRD diagnosis was associated with health and production outcomes of feedlot steers in a commercial feedlot.<p> A live animal percutaneous lung biopsy technique was developed to obtain a lung sample from the right middle lung lobe in intercostal space (ICS) 4 using a Bard® Magnum® reusable biopsy instrument and a modified 4-mm (8g) biopsy needle. The lung biopsy procedure was limited to 2 attempts per biopsy time. In the technique development, 34 animals chronically affected with BRD were utilized, 20 animals in the preliminary development followed by 14 additional animals in a commercial feedlot setting. The technique resulted in 1 fatality of 34 steers (2.9%) and lung parenchyma was harvested in 19 of 34 steers (55.9%) chronically affected with BRD. In addition, in the commercial feedlot setting this procedure was determined to take about 20 minutes per animal.<p> The final study was performed on one hundred feedlot steers considered at high risk of developing BRD from twenty pens within a commercial feedlot. Study animals were enrolled in three different groups: sick on arrival (ARR-SA) consisting of 27 study animals and 13 matched control animals; pen pulls with no fever (PP-NF) consisting of 14 study animals and matched 7 controls; and pen pulls with an undifferentiated fever (PP-UF) consisting of 26 study animals and 13 matched controls. Live animal percutaneous lung biopsies were collected from the right middle lung lobe at 3 different times within the first 30 days of the feeding period, about 2 weeks apart. All samples were histopathologically evaluated and were assessed for the presence of <i>Mycoplasma bovis</i>, <i>Mannheimia haemolytica</i>, Histophilus somni and bovine viral diarrhea virus with immunohistochemistry.<p> A total of 295 lung biopsies were performed yielding 210 (71.2%) lung samples that were sufficient for histopathological evaluation. A histopathology score was awarded to each biopsy based on certain histopathological lesions being present. Only 20 lung biopsy samples from 19 animals received a histopathology score (ie, pulmonary lesions were present) with the most common score being a 1 (maximum score is 20). There were too few lung biopsy samples with a histopathology score to reveal any association with subsequent health events.<p> Immunohistochemistry (IHC) was performed on all lung biopsies recovered yielding one lung sample to be positive for both <i>Mannheimia haemolytica</i> and <i>Mycoplasma bovis</i> from the PP-UF group. There were too few positive samples to reveal any association between IHC and histopathology score.<p> A post mortem evaluation was performed by a study veterinarian on all study animals who died or were humanely euthanized due to poor treatment response. In this study only 4 steers died or were euthanized due to poor treatment response and 3 control steers were humanely euthanized. There were too few animals to reveal any association between histopathology score and post mortem diagnosis.<p> On entry into the feedlot, weights between ARR-SA and the PP-UF and PP-NF groups were significantly different (p<0.05). This is likely an effect of the different processing groups of cattle. At study allocation, the body weights of ARR-SA and PP-UF, PP-UF and their matched controls, and PP-NF and their matched controls were also significantly different (p<0.05). This is likely due to the PP-UF and PP-NF groups experiencing illness for a longer period of time resulting in greater weight loss than the ARR-SA animals as well as the control animals, who were not clinically sick.<p> The live lung biopsy procedure utilized in this study did not appear to cause any long lasting adverse effects as the BRD case fatality rates from the study animals were comparable to the overall case fatality rates reported by the feedlot for fall placed calves. In fact, the study animals experienced a decreased fatality rate compared to the feedlots overall fatality rate. This may be due to the study animals inadvertently being monitored more closely as the pen checkers were aware of and participating in the study. On post mortem evaluation there was no evidence of adhesions at the biopsy site. This procedure was performed on 134 feedlot steers resulting in only 2 acute deaths as a direct result of the live animal percutaneous lung biopsy procedure.<p> The results of this study indicate that live animal, percutaneous lung biopsy can be performed safely on feedlot steers in a commercial feedlot with few clinical side effects. In this study there were only 2 fatalities in 134 steers (1.5%) due to the biopsy procedure or 2 fatalities per 349 sampling times (0.6%) This technique did not prove useful either as a diagnostic tool for the determination of early lung pathology in BRD or as prognostic indicator for health and production outcomes. However, this lung biopsy technique may be a useful diagnostic tool for chronic pneumonia assessment.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Alison P. Adams / Bovine respiratory disease (BRD) is the most common and costly disease affecting cattle in the world today. The disease was first described in the late 1800s and is one of the most extensively studied diseases of livestock. BRD accounts for 65 - 80% of the morbidity and 45 - 75% of the mortality in some feedlots. Outbreaks typically occur around 10 days after transportation with the majority of deaths occurring within the first 45 days of arrival. Bacterial pathogens, physiologic stressors, and concurrent viral infections are all important factors causing BRD; other factors include seasonality, heritability, and breed tolerance. Diagnostic and treatment measures are continually being critiqued and researched. Even with continued research and the administration of antibiotics, BRD still continues to be a problem for the beef industry. Remote early detection and previous calf history are two resources that can help feedlots diagnose the disease earlier, or prevent it entirely. Feeding behavior and physical exams of the calves can also aid in early detection. New antibiotics and treatment methods have been developed, but the BRD problem still exists. Since the disease is most problematic in feedlot cattle, treatment of a large number of cattle in this setting can be costly, and often, performance and carcass traits are also affected. New preventative measures will be crucial to the industry with the continued problems and consequences of BRD. Improved treatment options and enhanced diagnostic tools will also be imperative for the control and treatment of BRD in the future.

The study objective was to evaluate the effects of vaccination (respiratory and clostridial vaccination or no vaccination) and deworming (fenbendazole and levamisole or no deworming) of high risk stocker calves on-arrival on health and growth performance. Eighty sale barn origin calves were purchased three separate years (n=240) from local order buyer. Steers (n=61) and bulls (n=179) were received over three days (d -3 to -1). On d 0 calves were stratified by arrival BW and FEC into 20 pens of 4 calves each, and treatment was applied to pens in 2 x 2 factorial. Vaccination increased the likelihood of BRD 1.7 times (P=0.07) versus calves not vaccinated. Vaccination did not affect gain, but calves receiving dewormer had greater ADG than those not receiving dewormer. Calves that arrived uncastrated or with high fever (≥40.0°C) gained less and were 1.7 and 4.3 times more likely (P<0.10) to be treated for disease, respectively.

Bovine respiratory disease (BRD) complex is a multiactorial disease syndrome that results from various individual contributions and interactions of pathogen, host, and environmental/management factors. Despite the efforts in research, prevention and treatment, BRD remains a leading cause of economic loss in the cattle industry. While advances in therapeutics and new vaccines have been developed over the past 20 – 25 years, the incidence of respiratory disease does not appear to be on the decline, rather it is appears to be increasing. While bacterial and viral pathogens, and various stressors associated with BRD have been characterized, there are no animal models that can reproduce similar presentation of symptoms observed for BRD in the industry. Based on the etiology of BRD, a series of projects were designed to provide a better understanding of the individual and multiple contributions for the factors associated with the complex. It is believed that the viral pathogens or stressors can suppress immune defenses allowing opportunistic bacteria the ability to colonize and cause an infection. Therefore, trials investigating the individual contribution that varying doses of infectious bovine rhinotracheitis virus and transportation stress have on cattle were conducted. A final project investigating the combination effect of the bacterial pathogen M. haemolytica and activation of the hypothalamic-pituitaryrenal axis to elicit glucocorticoid release was evaluated. Ultimately, the research projects were designed to build upon each other to understand each component in the etiology of this disease.

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Robert L. Larson / Brad J. White / The diagnosis and prevention of bovine respiratory disease (BRD) is challenging due to the multifactorial nature of the disease. Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni are gram negative bacteria that are commonly considered three of the most important bacterial agents involved in the etiology of BRD; all three are also commensals in the upper respiratory tracts of healthy cattle. However, despite decades of study, questions still remain regarding the transmission dynamics and characterization of these bacteria, the ability of diagnostic sampling methods to accurately portray the causative bacteria, and ways to mitigate the effects of risk factors for BRD such as long-distance transportation. Through our research, we have demonstrated how variable the culture results of a single nasopharyngeal swab can be and the challenges of using an individual culture to truly represent animal M. haemolytica status. Additionally, comparison of the diagnostic performance of two antemortem sampling methods, nasopharyngeal swabs (NPS) and bronchoalveolar lavages (BAL), revealed high agreement, high negative predictive values of NPS for the presence of M. haemolytica, P. multocida, and H. somni in the lungs, and the potential for different susceptibility profiles from paired NPS and BAL samples. As agreement and predictive values can vary with disease prevalence, interpretation of diagnostic test results should be done carefully and with due consideration of the sample population in which the test is being applied. An investigation into cattle behavior following a relatively innocuous handling procedure indicated that some behaviors are altered after handling and restraint in a squeeze chute. Additionally, we demonstrated that cattle with different temperament scores may have different activity levels and spend different amounts of time within 1 m of the hay bunk, grain bunk, waterer, and shed after handling. Consequently, there is also the potential to improve upon disease detection algorithms by incorporating behavioral changes that may occur after handling events and the need for careful trial design when behavioral parameters are a trial outcome. Additionally, this study indicated that some behaviors may vary for calves that react differently when handled, which also has potential implications when behavior is considered a variable of interest. Examination of the potential for 1 mg/kg oral meloxicam administered pre-transport to mitigate the effects of long-distance transportation revealed that meloxicam did not have a statistically significant effect on the maintenance of leukocyte function or the reduction of inflammation during or after long-distance transportation in healthy steers. Finally, a report on two separate experiments regarding the effects of 1 mg/kg oral meloxicam administered pre-transport on the movement, feeding, and drinking behaviors and performance of transported and non-transported calves demonstrated that there was a significant day effect on behaviors in transported calves but meloxicam did not affect behavior or performance. However, meloxicam did modify the effect of day on daily distance traveled in non-transported calves but there were no significant within-day comparisons between non-transported meloxicam and non-transported control calves. These results do not provide evidence for the benefit of administering a single dose of 1 mg/kg oral meloxicam prior to long-distance transportation.

The objectives of this thesis were to investigate 1) the use of behavior and activity monitoring for the identification of heifers at risk of disease, 2) the use of group level management practices to reduce the risk of disease, and 3) the identification of long-term impacts of bovine respiratory disease complex (BRD). For objective 1, lying posture, a decreased willingness to approach an observer and high lethargy scores were associated with diarrhea in calves under 2 weeks of age and a high lethargy score in 4-6 week old calves was associated with decreased average daily gain (ADG) in the first 8 weeks of life (n = 744). In weaned calves (n = 74) increased activity (increase in steps and decrease in lying), standing at the bunk not eating, and lying far from other calves in the first 3 days post-weaning were associated with decreased post-weaning weight gain. For objective 2, separating social mixing from movement to a novel environment, and administering prophylactic antibiotics to calves at high risk of disease, were investigated. Both mixing and movement to a novel environment increased activity levels in newly weaned dairy calves (n = 64). When calves were mixed prior to movement to a novel environment they had a smaller increase in activity compared to calves that were simultaneously mixed and moved. No differences in weight gain or calf starter intake were observed. Administration of a prophylactic antibiotic, tulathromycin, to 3 day old calves upon arrival at a heifer raising facility (n = 788) and 8 week old calves at first movement to group housing (n = 1,392 ) was found to reduce diarrhea and otitis media, and BRD, respectively. Objective 3 was addressed by monitoring calves that received tulathromycin at 8 weeks of age to determine the long-term impacts of BRD. Bovine Respiratory Disease complex was associated with decreased growth to 9 months of age, decreased survival to first calving, increased risk of dystocia and a greater age at first calving. / Natural Sciences and Engineering Research Council of Canada & Pfizer Animal Health

Master of Science in Biomedical Sciences / Department of Clinical Sciences / Robert L. Larson / Bradley J. White / Feedlot cattle frequently endure high environmental temperature-humidity index conditions in the summer months within cattle feeding regions of North America. Heat stress develops when the total heat gain (combined effects of environmental and metabolic factors) exceeds an animal’s heat loss capabilities. The objective of my research was evaluating heat mitigation strategies and developing a practical method to identify animals that are of greatest risk of heat stress; thus improving animal welfare and performance. A number of heat abatement strategies have been utilized in US feedlots including shade, sprinklers, nutritional modifications, and misters. A literature review was performed using published journal articles demonstrated significant benefits of providing shade to feedlot cattle. Sprinkling the pen surface may be just as beneficial as sprinkling or misting cattle. Sprinkling the ground not only cooled the ground which increased the thermal gradient between lying cattle and the ground, but also provided increased thermal conductivity and better heat flow down that gradient. A study was performed to develop a noninvasive, remotely applied, practical method to identify animals at risk for heat stress. Infrared thermography images were obtained during the morning hours and pant scores obtained in the afternoon hours. Data mining techniques were employed to evaluate accuracy of potential classification methods to identify heat stress events in the afternoon based on the known morning data. Using infrared technology as a diagnostic test was not accurate for predicting heat stress events in the study presented. Finally a retrospective study of Kansas feedlot performance, medical and weather data was performed. Findings indicate that diagnostic counts of bovine respiratory disease are associated with elevated ambient temperature two days prior. In conclusion, heat stress in beef feedlot animals is an important area of research. Heat mitigation methods such as shade have been proven to be effective at reducing heat stress in beef feeder cattle. Further research is needed to evaluate the use of infrared technology to predict heat stress events in the feedlot setting.

Pneumonic pasteurellosis is a significant disease in beef production medicine. The most recent information suggests that this disease is a $700 million dollar per year economic burden in bovine food animal production The medical and pathological characteristics of this disease are well documented. Many pathological findings associated with pneumonic pasteurellosis may be explained by disruption of the pulmonary vascular adrenergic system. However, only a limited amount of research has addressed the adrenergic system and its relationship to the etiology and pathophysiology of this disease. In an attempt to further investigate the contributions of the vascular adrenergic receptor mechanism to the development of pneumonic pasteurellosis a series of six experiments have been completed. It is to be noted, that in 1999 the organism Pasteurella haemolytica was renamed Mannheimia haemolytica. The name change was based on the taxonomic features of the organism from other closely related organisms, in particular Pasteurella multocida.. The differences noted were identified and described by Dr. Mannheim in 1974. The familiarity of the past nomenclature and the lack of familiarity for the new nomenclature suggests that the more commonly recognized name of Pasteurella haemolytica should be used throughout this document. Scientific evidence suggests that the disruption of the normal homeostatic mechanisms of the pulmonary vasculature to beta adrenergic agents may be part of the etiology of pneumonic pasteurellosis. The dynamics and kinetics of the involvement of the beta receptors, following prophylactic vaccination and in the disease state, has yet to be fully investigated with respect to the events associated with pneumonic pasteurellosis. Evaluation of the time frame of the onset and duration of the events associated with the disruption of pulmonary vascular beta adrenergic receptor mechanisms revealed that an escalating level of dysfunction occurs over the first 24-48 hour period after exposure to parenteral Pasteurella haemolytica and lasts for at least 21 days. A component of P.haemolytica organism or contained in the vaccine using the organism is likely associated with the disruption of vascular beta adrenergic mechanism. This factor is, as yet, not specifically identified, however the likely culprit is the lipid A moiety of the endotoxin. Using the well defined and purified Escherichia coli endotoxin, trials were run to examine the effect of endotoxin on the pharmacological response of vascular associated beta adrenergic receptor mechanisms. The effects of Escherichia coli endotoxin, administered parenterally, on beta adrenergic receptor mechanisms were pharmacologically indistinguishable from those effects following parenterally administered Pasteurella haemolytica. The nature of the disruption in the beta adrenergic receptor remains a mystery. The receptor mechanism involves at least two second messengers to initiate vascular relaxation. Initial activation of the beta adrenergic receptor with a beta selective drug starts a cascade of events involving adenylylate cyclase and cyclic adenylylate monophosphate (cAMP) and nitric oxide. A disruption in the receptor mechanism, as a result of the parenteral administration of Pasteurella haemolytica, which is "upstream" of adenylyl cyclase, would result in a diminished amount of cAMP when compared to the unvaccinated negative controls. An investigation of cAMP accumulation, at the receptor level was inconclusive. The assessment of some previously used vaccines has demonstrated that there is an, as yet unidentified virulence factor, associated with these vaccines that results in the pharmacological disruption of beta adrenergic receptor mechanisms. Two newer vaccines, Once PMH® and One Shot® have been evaluated and there is evidence to suggest that these currently used vaccines also have the ability to disrupt beta adrenergic receptor mechanisms in rats. The effects of parenteral P. haemolytica on the alpha-2 adrenergic receptor mechanism, is described. The alpha-2 receptor mechanism, unlike the beta receptor mechanism appears to increase the amount of vasoconstriction. The possibility that the alpha-2 adrenergic receptor could also mediate vasorelaxation under certain conditions was investigated. The evidence suggests that in the presence of high alpha-1 mediated vascular tone, the alpha -2 receptor can cause vasorelaxation. Evidence, from other scientists active in this area of investigation, suggests that a vasorelaxation response may be mediated by nitric oxide. Elimination of the nitric oxide mediated relaxation may offer an explanation for the increased vasoconstriction noted with alpha-2 selective drugs after exposure to parenteral P. haemolytica. Finally, the importance of the beta adrenergic receptor to the disease process is addressed by elucidation of one of the mechanisms by which Micotil 300® (tilmicosin phosphate) acts to improve cattle with symptomatic pneumonic pasteurellosis. The rapid improvement of animals on Micotil 300®, with-in 24 hours suggests that there is a mechanism beyond the antimicrobial effect of the drug that mediates the clinical improvement. Evaluation of the effect of Micotil 300® demonstrates a pharmacologically measurable amount of beta adrenergic activity with respect to the bovine pulmonary artery and vein. Based on the conclusions drawn as a result of these experiments, the adrenergic system in general, and the beta adrenergic system in particular are important to the development of pneumonic pasteurellosis in cattle. The beta adrenergic system is affected by endotoxin. Further, these receptors maybe responsible for the mediation of the pathological and clinical signs associated with pneumonic pasteurellosis. In conclusion, these investigations have suggested, that it is likely that a disruption in the homeostatic mechanisms mediated by the beta and alpha-2 adrenergic receptors are intimately involved in the development of post vaccination receptor failure as well as the pathophysiology associated with pneumonic pasteurellosis in cattle. / Ph. D.