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.     

Pharmacokinetic profiles of the two major active metabolites of metamizole (dipyrone) in cats following three different routes of administration

This study was performed to determine pharmacokinetic profiles of the two active metabolites of the analgesic drug metamizole (dipyrone , MET), 4‐methylaminoantipyrine (MAA), and 4‐aminoantipyrine (AA), after intravenous (i.v., intramuscular (i.m.), and oral (p.o.) administration in cats. Six healthy mixed‐breed cats were administered MET (25 mg/kg) by i.v., i.m., or p.o. routes in a crossover design. Adverse clinical signs, namely salivation and vomiting, were detected in all groups (i.v. 67%, i.m. 34%, and p.o. 15%). The mean maximal plasma concentration of MAA for i.v., i.m., and p.o. administrations was 148.63 ± 106.64, 18.74 ± 4.97, and 20.59 ± 15.29 μg/ml, respectively, with about 7 hr of half‐life in all routes. Among the administration routes, the area under the plasma concentration curve (AUC) value was the lowest after i.m. administration and the AUC_EV/i.v. ratio was higher in p.o. than the i.m. administration without statistical significance. The plasma concentration of AA was detectable up to 24 hr, and the mean plasma concentrations were smaller than MAA. The present results suggest that MET is converted into the active metabolites in cats as in humans. Further pharmacodynamics and safety studies should be performed before any clinical use.     

Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.     

CD117‐ and vimentin‐positive telocytes in the bovine teat sphincter

Mastitis is a common economically relevant problem in dairy farming. As the major entry for pathogens is the papillary duct, one of the first defence mechanisms is the teat sphincter. This sphincter shows a rhythmic contractility of yet unknown origin. Searching for possible modulatory pacemaker cells, teat sphincters of eight cows were stained immunohistochemically with antibodies against CD117 and vimentin and evaluated microscopically for the presence of telocytes. CD117‐ and vimentin‐positive telocytes with telopodes were found in close contact with smooth muscle cells. Our findings present a first evidence of telocytes in the teat of bovines.     

Hyperglycaemia in transition dairy cows: Effects of lactational stage and conjugated linoleic acid supplementation on glucose metabolism and turnover

Supplementing conjugated linoleic acid ( CLA ) is supposed to spare glucose due to the milk fat‐depressing effect of the trans ‐10, cis ‐12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC ) in weeks ?2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid‐encapsulated CLA (6.8 g trans ‐10, cis ‐12 and 6.6 g of the cis ‐9, trans ‐11 CLA isomer; CLA ; n  = 11) or with 56 g of control fat ( CON ; n  = 11). From week ?3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI ) were recorded daily, while body weight (BW ) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC . Plasma was analysed for concentrations of glucose, fatty acids (FFA ), beta‐hydroxybutyrate (BHB ), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week ?2 although glucose target concentration achieved during the steady‐state period was similar for all three HGC . Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation.     

Evaluation of β‐carotene assimilation in leopard geckos (Eublepharis macularius)

Although leopard geckos (Eublepharis macularius) are commonly kept under human care, their vitamin requirements are largely unknown. Many invertebrate preys display a low vitamin A concentration; thus, gut‐loading insects with vitamin A or carotenoids is a common practice. The objective of this prospective experimental study was to investigate whether dietary supplementation with β‐carotene, including prey gut‐loading, leads to sufficient vitamin A hepatic storage and prevents epithelial squamous metaplasia development in leopard geckos. Ten clinically healthy female leopard geckos were randomly divided in two groups with various supplementations: a group receiving vitamin A supplementation and a group receiving β‐carotene. Insects were gut‐loaded continuously with a supplement containing vitamin A or β‐carotene, depending on the group. Oral supplementation with cod liver oil or carrot juice was administered weekly to each lizard from “vitamin A group” and “carotenoid group” respectively. After 10 weeks of supplementation, surgical hepatic biopsies were obtained in three geckos of each group while the two remaining geckos were euthanized to undergo complete necropsy. Hepatic vitamin A concentration was determined for each lizard (n = 10) by ultra‐performance liquid chromatography. Histopathology revealed hepatocellular vacuolization and vitellogenic follicles in five females. Epithelial squamous metaplasia was not observed in any of the geckos. Hepatic vitamin A concentration was significantly higher in the carotenoid‐supplemented group than in the vitamin A‐supplemented group (p = 0.03). Our results suggest that in leopard geckos, dietary supplementation with β‐carotene allows sufficient vitamin A hepatic storage.     

In ovo feeding of nutrients and its impact on post‐hatching water and feed deprivation up to 48 hr,energy status and jejunal morphology of chicks using response surface models

A Box–Behnken design (BBD) in a response surface methodology (RSM) was used to investigate the response of broiler chicks to in ovo feeding (IOF) of beta‐hydroxy beta‐methylbutyrate (HMB), dextrin and the timing of the first water and feed deprivation. On day 18th of incubation, 1,500 eggs were randomly assigned to 15 experimental runs of BBD, each with 4 replicates, as 3 levels IOF of HMB (0%, 0.5% and 1%) and dextrin (0%, 20% and 40%), and 3 levels of the first water and feed deprivation (6, 27 and 48 hr). Day‐old chicks from each replicate were then used to assess the effect of IOF and time first water and feed access on chick's responses. The IOF of dextrin leads to respectively 9.7%–15.5% lower hatchability for 20% and 40% inclusion (p < .05), whereas HMB inclusion appeared with no effect on hatchability (p > .05). Administration of dextrin or HMB into the amnion of embryos elevated length, width and surface area of villus, and increased glycogen content of liver and breast (p < .05). In all parameter models, the linear terms showed highest contribution (R² = 0.81–0.97) to explain existing variation in chick's responses. The first water and feed deprivation had largest effect on BW2 and glycogen content of liver and breast. It is concluded that if possible, place chicks before 7 hr of hatch to preserve BW loss and have maximum response from IOF. If not possible, use IOF with 40% dextrin + 0.5% HMB to preserve gut integrity and energy status up to 48 hr. This should give advantage to chicks to recover fast after feeding, but that would have to be confirmed by trials growing birds to slaughter age.