Evaluation of antibodies in cerebrospinal fluid for the diagnosis of tick-borne encephalitis in dogs

Tick-borne encephalitis (TBE) is caused by the neurotropic tick-borne encephalitis virus (TBEV). In dogs, this virus may affect the central nervous system (CNS), causing meningoencephalitis, meningomyelitis, radiculitis or any combination of these. Diagnosis of TBE relies on a combination of clinical signs of CNS disease and laboratory findings, including CSF pleocytosis and serum TBEV antibody titers. Exposure to TBEV does not necessarily cause clinical disease, and seroprevalence has been reported as high as 40% in endemic areas. This causes concerns of over-diagnosing TBE in dogs with CNS disease. By examining TBEV antibodies in dogs with and without neurological disease in a TBEV endemic area, this study aimed to evaluate the diagnostic value of TBEV antibodies in the cerebrospinal fluid (CSF) in dogs. Eighty-nine dogs were included in the study, 56 with neurological disease and 33 neurologically normal control dogs. A positive TBEV CSF and serum IgG antibody titer (> 126 U/mL) was found in 3/89 dogs (3.4%). A positive serum TBEV antibody titer was found in 11 of the 89 dogs (12.4%). None of the control dogs showed a positive CSF antibody titer, whilst two showed positive serum concentrations. A positive CSF IgG antibody titer supports a clinical diagnosis of TBE in patients with acute onset of CNS disease and may help reduce the risk of over-diagnosis

Impact of blood tube additives and timing of sampling on blood taurine concentrations in clinically healthy dogs

Introduction: Dilated cardiomyopathy can be associated with taurine deficiency in dogs. Blood taurine concentrations can be analyzed in whole blood (WB) and plasma. The study objectives were to investigate agreement between taurine concentrations measured in WB, heparin plasma, and EDTA plasma, deter-mine intraindividual variation in healthy dogs, and evaluate if time from feeding to sampling impacts concentrations. Animals: 10 English Cocker spaniels and 10 dogs of various breeds. Materials and methods: Dogs were fasted 12 h prior to initial blood sampling, and the blood was collected at five occasions over 8 h. Food was offered immediately after first and 1 h after fourth sampling time point. Results: Agreement between taurine concentrations in EDTA plasma and hepari-nized plasma was good (mean difference 4.5 nmol/mL, 95% confidence interval (CI) 36.8-45.8 nmol/mL). WB concentrations were systematically higher than EDTA and heparin plasma concentrations (mean difference 132.7 nmol/mL, 95% CI 23.6-241.8 nmol/mL, and 127.6 nmol/mL, 95% CI 28.6-226.6 nmol/mL, respectively, all P < 0.001). Intraindividual daily variations in taurine concentration were seen in all additives, with largest variations in plasma (P < 0.001). Taurine concentration in heparinized plasma was higher at first and fifth sampling time points compared to the fourth (P 1/4 0.014). Discussion: Agreement was found between taurine concentrations measured in dif-ferent additives, with expected higher concentration in WB than plasma. Taurine concentrations measured in heparinized plasma varied with sampling time point. Intraindividual daily variations were observed in all additives, but mainly in plasma samples. Conclusion: Taurine concentrations in dogs with suspected deficiency should be in-terpreted with caution. 2022 The Authors. Published by Elsevier B.V

Effect of feline characteristics on plasma N-terminal-prohormone B-type natriuretic peptide concentration and comparison of a point-of-care test and an ELISA test

Background: Increased plasma concentration of N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) can be detected in cats with cardiac disease. Potential effects of feline characteristics on NT-proBNP concentration may influence clinical usefulness. Objectives: To evaluate potential effects of feline characteristics on NT-proBNP plasma concentration and to compare NT-proBNP plasma concentrations in healthy cats with results in hypertrophic cardiomyopathy (HCM) cats with or without left atrial enlargement (LAE) using an ELISA and a point-of-care test (POCT), and assess if POCT results reflect ELISA results. Animals: One hundred healthy cats of 3 breeds and 39 HCM cats were included. Methods: Diseases other than HCM were excluded by physical examination, blood pressure measurement, echocardiography, hematology, and serum biochemistry.Results Higher NT-proBNP concentrations were found in males than in females in healthy (P = .005) and in HCM cats (P = .0021), but breed had no effect on NT-proBNP concentrations. Using >= 100 pmol/L as a cutoff for abnormal samples, ELISA and POCT had similar sensitivity (SE; 72 and 74%) and specificity (SP; 97 and 98%) for detecting cats with HCM, cats with HCM and LAE (SE, both 100%; SP, 97 versus 98%), and cats with HCM without LAE (SE, both 69%; SP, 97 versus 98%), respectively, when compared to healthy cats. Conclusions and Clinical Importance: Breed had no effect on plasma NT-proBNP concentrations, but higher concentrations were found in male than in female cats. The ELISA and POCT had similar SE and SP for detecting HCM. Both tests could identify all HCM cats with LAE but not all HCM cats without LAE

Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy

Objectives The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables. Methods Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE. Results In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P <= 0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003). Conclusions and relevance Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM

Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy

Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies