Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with Atrial Fibrillation

Background

Atrial fibrillation (AF) usually is associated with a rapid ventricular rate. The optimal heart rate (HR) during AF is unknown.

Hypothesis/Objectives

Heart rate affects survival in dogs with chronic AF.

Animals

Forty‐six dogs with AF and 24‐hour ambulatory recordings were evaluated.

Methods

Retrospective study. Holter‐derived HR variables were analyzed as follows: mean HR (meanHR, 24‐hour average), minimum HR (minHR, 1‐minute average), maximum HR (maxHR, 1‐minute average). Survival times were recorded from the time of presumed adequate rate control. The primary endpoint was all‐cause mortality. Cox proportional hazards analysis identified variables independently associated with survival; Kaplan‐Meier survival analysis estimated the median survival time of dogs with meanHR <125 bpm versus ≥125 bpm.

Results

All 46 dogs had structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46 received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median time to all‐cause death was 524 days (Interquartile range (IQR), 76–1,037 days). MeanHR was 125 bpm (range, 62–203 bpm), minHR was 82 bpm (range, 37–163 bpm), maxHR was 217 bpm (range, 126–307 bpm). These were significantly correlated with all‐cause and cardiac‐related mortality. For every 10 bpm increase in meanHR, the risk of all‐cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17–1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was significantly longer (1,037 days; range, 524‐open) than meanHR ≥125 bpm (n = 23; 105 days; range, 67–267 days; P = 0.0012). Mean HR was independently associated with all‐cause and cardiovascular mortality (P < 0.003).

Conclusions and Clinical Importance

Holter‐derived meanHR affects survival in dogs with AF. Dogs with meanHR <125 bpm lived longer than those with meanHR ≥ 125 bpm.     

Diagnostic imaging of oronasal fistulas in a dachshund

Oronasal fistula development is described anecdotally as a common disease process in the dachshund but little is known about its imaging appearance. This case report describes the clinical presentation, computed tomography (CT) characterisation, dental radiograph confirmation and treatment of bilateral oronasal fistulas in a 14‐year‐old dachshund.     

The evolution and application of enzymes in the animal feed industry: the role of data interpretation

ABSTRACT

1. Enzymes have been used commercially for nearly 40 years and save significant costs through sparing of expensive nutrients but the mechanism by which this is achieved is still debated.

2. The research focused on non-starch polysaccharidase (NSPase) enzymes is used as an example of where greater progress could have been made if the details of the work had been described more fully and the analysis of the data generated had been broader in scope and more critical.

3. Lack of standardisation of the details presented in the materials and methods has been identified as a significant barrier to meaningful retrospective analysis and thus limits advances in the understanding of the mode of action of these enzymes.

4. The identity of the enzyme employed and its activity is often lacking, and more importantly the purity is rarely disclosed. Contaminant activities which are neither listed nor assayed could play a significant role in the responses observed.

5. The dose optimum of most enzymes is often considerably higher than that employed in most studies. Thus studies claiming synergy between two ‘activities’ should ensure that the response is not related to each enzyme simply augmenting the dose of just one activity in the finished feed. This is a common problem, and coupled with the lack of factorial experiments to justify the presence of each enzyme in a multi-enzyme product, it is not surprising that there is still debate as to whether single or multi-enzymes are best suited poultry rations.

6. The three proposed mechanisms for NSPases (viscosity, cell wall and prebiotic) are discussed, and along with their strengths and weaknesses it is suggested that a re-evaluation of each is needed. Viscosity may have to be re-evaluated as being a function not only of the cereal being fed, but of the age of the animal as well. The cell wall theory as described is poorly modelled in vitro and hence the validity of these data is questioned. The prebiotic theory may need significant modification as it appears that the quantities of oligomers produced are insufficient to generate the additional volatile fatty acids (VFA)’s reported. It is likely that all three mechanisms play a role in the responses observed, but the prebiotic mechanism probably plays by far the most important part in low viscosity diets.

7. Future research would be improved if it considered all potential mechanisms when designing a trial. Significant failings are apparent as a result of adherence to tenets in explanation of the results. Most importantly, it should be emphasised that a hypothesis is there to be tested, not defended.     

Efficacy of a mephentermine‐based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY^® INJETÁVEL (POT), a mephentermine‐based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized‐complete‐block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume‐matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six‐day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end‐tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady‐state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post‐treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dt_max: +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dt_min: +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo‐control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.     

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.