Amy E. DeClue

Evaluation of circulating amino terminal-pro-B-type natriuretic peptide concentration in dogs with respiratory distress attributable to congestive heart failure or primary pulmonary disease

OBJECTIVE To evaluate assessment of circulating amino terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration as a means to discriminate between congestive heart failure and primary pulmonary disease in dogs. DESIGN Prospective case series. ANIMALS 46 dogs with signs of respiratory distress or coughing. PROCEDURES All dogs underwent physical and thoracic radiographic examinations. Dogs with evidence of heart disease (eg, murmur, arrhythmia, or large cardiac silhouette detected by radiography) also underwent echocardiography. Dogs with no evidence of heart disease or failure were included if they underwent bronchoalveolar lavage (with cytologic examination and bacterial culture of the lavage fluid). Blood samples for NT-proBNP assay were obtained within 12 hours of the diagnosis of heart failure or prior to bronchoalveolar lavage in dogs with primary pulmonary disease. Circulating concentrations of NT-proBNP were compared between groups and correlated with radiographic and echocardiographic measures of cardiac size. RESULTS Congestive heart failure and primary pulmonary disease were diagnosed in 25 and 21 dogs, respectively. Dogs with congestive heart failure had significantly higher median serum or plasma NT-proBNP concentration (2,554 pmol/L; interquartile [25% to 75%] range, 1,651.5 to 3,475.5 pmol/L) than dogs with primary pulmonary disease (357 pmol/L; interquartile range, 192.5 to 565.5 pmol/L). Radiographic vertebral heart score and echocardiographic left atrial-to-aortic diameter ratio were not correlated with NT-proBNP concentration. Left ventricular end-diastolic diameter (measured echocardiographically) and NT-proBNP concentration were weakly correlated. CONCLUSIONS AND CLINICAL RELEVANCE Serum or plasma NT-proBNP concentration assessment may be useful for discrimination of congestive heart failure from primary pulmonary disease in dogs with respiratory distress or cough.

Effects of subanesthetic doses of ketamine on hemodynamic and immunologic variables in dogs with experimentally induced endotoxemia

OBJECTIVE To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS 9 mixed-breed dogs. PROCEDURES In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.

Age‐associated changes to pathogen‐associated molecular pattern‐induced inflammatory mediator production in dogs

OBJECTIVE To determine whether older dogs will have a more pronounced pro-inflammatory response and blunted anti-inflammatory response to pathogen-associated molecular patterns (PAMPs) compared with younger dogs. DESIGN Prospective. SETTING University teaching hospital. ANIMALS Thirty-eight privately owned sexually altered dogs of various ages. INTERVENTIONS Blood was collected for HCT, WBC count, plasma biochemical analysis, and whole blood culture. Whole blood was stimulated with lipopolysaccharide (LPS) or, lipoteichoic acid or, peptidoglycan or, addition of phosphate-buffered saline. Tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 production from whole blood were compared among young, middle aged, and geriatric dogs. MEASUREMENTS AND MAIN RESULTS LPS, lipoteichoic acid, and peptidoglycan stimulated significant TNF, IL-6, and IL-10 production from canine whole blood compared with phosphate-buffered saline. Whole blood from geriatric dogs had a blunted IL-10 response to LPS stimulation and middle-aged dogs had increased LPS-induced TNF production compared with the other groups. CONCLUSION PAMPs from gram-positive and gram-negative bacteria stimulate TNF, IL-6, and IL-10 production from canine whole blood. The inflammatory mediator response to PAMPs from gram-negative bacteria alters with age and may be one factor contributing to mortality in geriatric dogs with sepsis.Objective – To determine whether older dogs will have a more pronounced pro-inflammatory response and blunted anti-inflammatory response to pathogen-associated molecular patterns (PAMPs) compared with younger dogs. Design – Prospective. Setting – University teaching hospital. Animals – Thirty-eight privately owned sexually altered dogs of various ages. Interventions – Blood was collected for HCT, WBC count, plasma biochemical analysis, and whole blood culture. Whole blood was stimulated with lipopolysaccharide (LPS) or, lipoteichoic acid or, peptidoglycan or, addition of phosphate-buffered saline. Tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 production from whole blood were compared among young, middle aged, and geriatric dogs. Measurements and Main Results – LPS, lipoteichoic acid, and peptidoglycan stimulated significant TNF, IL-6, and IL-10 production from canine whole blood compared with phosphate-buffered saline. Whole blood from geriatric dogs had a blunted IL-10 response to LPS stimulation and middle-aged dogs had increased LPS-induced TNF production compared with the other groups. Conclusion – PAMPs from gram-positive and gram-negative bacteria stimulate TNF, IL-6, and IL-10 production from canine whole blood. The inflammatory mediator response to PAMPs from gram-negative bacteria alters with age and may be one factor contributing to mortality in geriatric dogs with sepsis.

Effects of fluticasone propionate dosage in an experimental model of feline asthma

Cats with inflammatory bronchial disease are usually treated with glucocorticoid (GC) drugs to reduce airway inflammation. Inhalant GC delivery can preserve airway effects while systemic effects are minimized. An appropriate dosage regimen for inhaled GC in cats has not been investigated. A blinded, randomized, cross-over study design was used to investigate the ability of three different dosages of the inhalant GC fluticasone propionate delivered by metered dose inhaler to ameliorate eosinophilic airway inflammation in cats with experimentally induced allergic airway inflammation. Further, suppression of the hypothalamic–pituitary–adrenal axis (HPAA) at each dose was assessed. Fluticasone administered at dosages of 44, 110, or 220 μg q 12 h reduced airway eosinophilia by 74%, 82%, or 81%, respectively (no difference). None of the dose regimens tested caused HPAA suppression. We conclude that a twice daily dosage of 44 μg fluticasone should be evaluated for the management of cats with naturally occurring inflammatory bronchial disease.

Immunomodulatory effects of opioids.

Objective – To review the immunomodulatory effects of opioids. Data Sources – Original research publications and review articles using the PubMed search engine with the following keywords – opioids, morphine, immuomodulation, and immunosuppression. Veterinary and Human Data Synthesis – Opioids have been shown to modulate the immune system in animal models by affecting both the acquired and innate arms of the immune system. Natural killer cell activity, T-cell proliferation, antibody production, phagocytic cell function, and cytokine production have all been shown to be affected by opioids. Many of these effects are reversed by opioid antagonists. Opioids have also been shown to induce sepsis in laboratory animals. Opioid administration alters immune parameters in healthy humans at analgesic doses and may increase the risk of infection in some patient populations. Conclusions – While opioids remain the most powerful and widely used analgesics available, their negative effects on the immune system are well established in the laboratory setting. Thoughtful consideration should be given to the use of certain opioids in critically ill patients, especially those with pre-existing immunocompromise.OBJECTIVE To review the immunomodulatory effects of opioids. DATA SOURCES Original research publications and review articles using the PubMed search engine with the following keywords--opioids, morphine, immuomodulation, and immunosuppression. VETERINARY AND HUMAN DATA SYNTHESIS: Opioids have been shown to modulate the immune system in animal models by affecting both the acquired and innate arms of the immune system. Natural killer cell activity, T-cell proliferation, antibody production, phagocytic cell function, and cytokine production have all been shown to be affected by opioids. Many of these effects are reversed by opioid antagonists. Opioids have also been shown to induce sepsis in laboratory animals. Opioid administration alters immune parameters in healthy humans at analgesic doses and may increase the risk of infection in some patient populations. CONCLUSIONS While opioids remain the most powerful and widely used analgesics available, their negative effects on the immune system are well established in the laboratory setting. Thoughtful consideration should be given to the use of certain opioids in critically ill patients, especially those with pre-existing immunocompromise.

Asthma in humans and cats: Is there a common sensitivity to aeroallegens in shared environments? ☆

Cats spontaneously develop eosinophilic airway inflammation and airway hyperreactivity that is very similar to human allergic asthma. In addition, household cats share environmental exposures to aeroallergens with humans. We review the scientific literature concerning the pathophysiology of feline asthma, including similarities to human asthma and evidence regarding environmental aeroallergen triggers. Results of pathophysiological studies suggest important similarities between human and feline responses to inhaled allergens. Only a few studies were found that examined the development of disease in cats to environmental aeroallergens. Limited evidence suggests that some environmental allergens can cause disease in both cats and humans. It appears that there is a need for greater communication between human and animal health professionals regarding environmental causes of asthma. Specifically, additional research into linkages between human and feline asthma using both molecular techniques and clinical epidemiological approaches could lead to improved understanding of the environmental risks. Finally, there should be consideration of use of naturally affected and/or experimentally induced (using clinically relevant allergens) asthmatic cats in preclinical trials for novel therapeutic interventions.

The Tyrosine Kinase Inhibitor Masitinib Blunts Airway Inflammation and Improves Associated Lung Mechanics in a Feline Model of Chronic Allergic Asthma

Background: Blockade of tyrosine kinase signaling by masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, can modulate allergic airway inflammation, but effects on lung mechanics have not been well characterized. We hypothesized masitinib would decrease airway eosinophilia and consequently improve pulmonary mechanics in a feline allergic asthma model. Methods: Asthma was induced in 12 cats using Bermuda grass allergen (BGA). Cats received 50 mg/day oral masitinib or placebo. Bronchoalveolar lavage fluid (BALF) was analyzed for eosinophils, total protein (TP) and BGA-specific IgE. Ventilator-acquired mechanics after methacholine (MCh) challenge determined MCh concentration needed to increase baseline airway resistance by 200% (EC200Raw), positive end expiratory occlusion pressure (PEEP) and end inspiratory breath hold pressure (Pplat). An inverse correlate of respiratory system compliance Pplat-PEEP was also calculated. Data were analyzed using the Wilcoxon test, with one-tailed significance set at p < 0.1. Results: After 4 weeks, percent eosinophils in BALF was lower in masitinib-treated cats (7 ± 9%) versus controls (30 ± 27%, p = 0.023). BALF TP significantly differed (p = 0.047) between groups, decreasing with masitinib and increasing with placebo. BALF BGA-specific IgE was unaffected by masitinib. Both groups showed an improvement in EC200Raw (masitinib, p = 0.015; control, p = 0.078) but no significant change in PEEP after 4 weeks. Masitinib-treated cats demonstrated decreased Pplat (p = 0.033) and Pplat-PEEP (p = 0.075) at week 4, suggesting an improvement in respiratory compliance. Conclusions: Masitinib reduced BALF eosinophilia and TP, indicating improved airway inflammation and edema, and improved Pplat and Pplat-PEEP, suggesting benefit to respiratory compliance influenced by airway inflammation/edema. Masitinib deserves further study in humans with chronic allergic asthma.

Comparison of intradermal skin testing (IDST) and serum allergen-specific IgE determination in an experimental model of feline asthma.

Intradermal skin testing (IDST) and allergen-specific IgE determination are used to determine allergen sensitization. In cats, studies have found poor correlation between the two tests. However, these studies were mainly conducted in pet cats sensitized to unknown allergens with unknown dose and duration of exposure. We hypothesized that in an experimental model of allergic sensitization where these variables are controlled, IDST would demonstrate greater sensitivity and specificity than would serum allergen-specific IgE determination. A model of feline asthma employing Bermuda grass allergen (BGA) or house dust mite allergen (HDMA) was used to test the hypothesis. Thirteen cats were assigned to undergo sensitization to BGA, HDMA or saline (placebo). Bronchoalveolar lavage fluid confirmed development of an asthmatic phenotype. Serum collection and IDST were performed on D0, D28 and D50. A portion of serum was pooled, and an aliquot heat inactivated (HI) to destroy IgE. Individual, pooled, and pooled HI samples were used for allergen-specific IgE determination using an Fc epsilon R1 alpha-based ELISA; pooled samples were also analyzed using an enzymoimmunometric assay. Sensitivity (SE), specificity (SP), and positive and negative predictive values (PPV and NPV) were calculated for IDST and for BGA- and HDMA-specific IgE. Combined results for IDST found SE=90.9%, SP=86.7%, PPV=83.3%, and NPV=92.9%. For ELISA-based serum IgE testing, the SE=22.7%, SP=100%, PPV=100% and NPV=63.8%. The enzymoimmunometric assay did not detect sensitizing IgE, but did detect IgE reactivity to a variety of irrelevant allergens (even in HI samples). Sensitivity of IDST was greater than sensitivity of serum IgE measurement supporting use as a screening test for aeroallergens. Both IDST and allergen-specific IgE determination via ELISA were specific; either test can be used to guide selection of allergens for immunotherapy. The enzymoimmunometric assay was unreliable and cannot be recommended.

Continuous Glucose Monitoring in Dogs and Cats

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.

Pathogen associated molecular pattern motifs from Gram-positive and Gram-negative bacteria induce different inflammatory mediator profiles in equine blood

Although the incidence of Gram-positive infection in horses is increasing, little is known about differences in inflammatory response between Gram-positive and Gram-negative organisms in this species. Equine blood was stimulated with components of both Gram-negative and Gram-positive organisms: lipopolysaccharide (LPS); lipoteichoic acid (LTA); peptidoglycan (PG); with combinations of LPS, LTA and PG; and with phosphate buffered saline (control). LPS, LTA and PG stimulated tumor necrosis factor (TNF) and interleukin (IL)-6 production but only LTA and PG stimulated IL-1β production from whole blood. LPS was a more potent inducer of TNF than either LTA or PG and both LPS and LTA were more potent inducers of IL-6 than PG. Generally, combinations of pathogen associated molecular patterns (PAMPs) did not elicit greater inflammatory mediator responses when compared to LPS, LTA or PG alone, although there was some synergism between the effects of LPS and LTA. The repertoire of inflammatory mediators provoked by Gram-positive vs. Gram-negative motifs is thus distinctly different. As novel immunomodulatory therapies are developed for use in the horse, care should be exercised when applying treatments for endotoxemia to animals with Gram-positive infections given the different cytokine response profiles.