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 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

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

Peer reviewe

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study

The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF)