Reference interval, longitudinal variability and reliability of activated clotting time in healthy dogs using a point-of-care analyser.

BACKGROUND: Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy. OBJECTIVES: To determine a reference interval (RI) for ACT in dogs using a point-of-care analyser, to quantify intra-subject within- and between-day variability, to quantify analyser reliability and inter-analyser agreement and to study the influence of a delay in measurement. METHODS: Forty-two healthy dogs were included. Measurements were performed on fresh venous blood using the i-STAT 1 analyser. The RI was determined using the Robust method. Intra-subject within-day variability and between-day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter-analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6). RESULTS: Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra-subject within- and between-day variability were 8.1% and 10.4%, respectively, resulting in a significant between-day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis. CONCLUSIONS: Our study provides an RI for ACT in healthy dogs using the i-STAT 1 and suggests low intra-subject within- and between-day variability. Analyser reliability and inter-analyser agreement were good; however, analysis delay and between-day differences could significantly influence ACT results.

Assessment of Cardiotoxicity after a Single Dose of Combretastatin A4-Phosphate in Dogs Using Two-Dimensional Speckle-Tracking Echocardiography.

Combretastatin A4-phosphate (CA4P) is a vascular disrupting agent that was recently described for the treatment of solid canine tumors. Conventional echocardiography and pulsed wave tissue Doppler imaging did not reveal cardiotoxicity in dogs, however, the gold standard for assessing myocardial damage in humans receiving cardiotoxic chemotherapeutics is two-dimensional speckle-tracking echocardiography. The current study evaluated the cardiotoxic effect of a single dose of CA4P in dogs using peak systolic strain measurements and the variability of these measurements. Echocardiographic examinations of seven healthy beagles and five canine cancer patients that received CA4P were retrospectively reviewed. Peak systolic regional longitudinal strain (LSt), peak systolic regional circumferential strain (CSt), and peak systolic regional radial strain (RSt) were measured before and 24 h after administration of CA4P. Peak systolic strain measurements were compared to serum cardiac troponin I (cTnI). To quantify intra- and inter-observer measurement variability, seven echocardiographic examinations were selected and each strain parameter was measured by three observers on three consecutive days. After CA4P administration, the median LSt and CSt values decreased by 21.8% (p = 0.0005) and 12.3% (p = 0.002), respectively, whereas the median RSt values were not significantly different (p = 0.70). The decrease in LSt was correlated with increased serum cTnI values (Spearman rho = -0.64, p = 0.02). The intra-observer coefficients of variation (CV) were 9%, 4%, and 13% for LSt, CSt, and RSt, respectively, while the corresponding interobserver CVs were 11%, 12%, and 20%. Our results suggest that regional peak systolic strain measurements may be useful for the early detection of cardiotoxicity that is caused by vascular disrupting agents and that LSt may be promising for the follow-up of canine cancer patients.

Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats.

BACKGROUND: In people and dogs, torasemide has higher bioavailability, longer half-life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited. OBJECTIVE: To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin-angiotensin-aldosterone system (RAAS). ANIMALS: Six clinically healthy adult European shorthair cats. METHODS: Randomized 4-period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model. RESULTS: Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half-life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose-dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: A single torasemide dose leads to a significant increase in diuresis and renin-angiotensin-aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.

Diagnosis and management of arrhythmias in dogs: A cross-sectional online survey among Flemish veterinary practitioners.

Background: Diagnosis as well as management of arrhythmias in dogs can be challenging for veterinary practitioners. The aim was to describe ECG availability and use, as well as the diagnostic and therapeutic experiences and preferences of Flemish veterinarians regarding cardiac arrhythmias in dogs. Methods: Cross-sectional online survey among veterinarians in Flanders (Belgium). Results: An ECG device was available for 55 out of 102 respondents (54%) and 41 (43%) claimed to use it in case of arrhythmia suspicion. Insufficient knowledge about ECG interpretation and immediate patient referral upon detection of an abnormal heart rhythm were the most important reasons for not having, or not using, an ECG. About half of the respondents (56%) had never used anti-arrhythmic drugs in dogs, although only a few reported having had a negative experience. Frequently provided reasons for not using anti-arrhythmic drugs included insufficient knowledge and a low number of dogs with arrhythmias. Conclusion: Most veterinarians reported having little or no expertise with arrhythmias in dogs. Electrocardiogram availability and use among respondents was moderate and too often restricted by insufficient ECG interpretation skills. Continued efforts are needed to increase the confidence and knowledge of veterinarians about arrhythmias in dogs.

Sudden cardiac death: A comparative review of humans, dogs and cats.

Sudden death is one of the most common causes of death in humans in Western countries. Approximately 85% of these cases are of cardiac origin. In dogs and cats, sudden cardiac death (SCD) also commonly occurs, but fewer pathophysiological and prevalence data are available. Both structural, primarily 'electrical' and ischemic heart diseases are known to cause SCD, many of which share similar underlying arrhythmogenic mechanisms between humans and companion animals. As for underlying genetics, numerous mutations on multiple loci have been related to SCD in humans, but only a few mutations associated with dilated cardiomyopathy and SCD have been identified in dogs, e.g. in the phospholamban and titin genes. Information published from human medicine can therefore inform future veterinary studies, but also dogs and cats could act as spontaneous models of SCD in humans. Further research in both fields is therefore warranted to better understand the pathophysiology, genetics, and prevention of SCD.