The use of rivaroxaban for the treatment of thrombotic complications in four dogs.

OBJECTIVE: To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis. CASE SERIES SUMMARY: This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing. NEW OR UNIQUE INFORMATION PROVIDED: This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol.

Comparison of serum fatty acid concentrations in cats with hypertrophic cardiomyopathy and healthy controls.

n-3 fatty acids have some benefits in humans and dogs with cardiac disease, and plasma n-3 fatty acid concentrations have been shown to be decreased in dogs with congestive heart failure (CHF). However, there are no published studies reporting fatty acid concentrations in cats with cardiac disease. Therefore, the goal of this study was to compare serum fatty acid concentrations in normal cats and cats with hypertrophic cardiomyopathy (HCM), and determine if fatty acid concentrations correlate with left atrial size or the presence of CHF. Serum fatty acid concentrations were measured in normal cats and cats with HCM by gas chromatography. Twenty-three cats with HCM and 20 healthy controls were enrolled. Compared with healthy controls, cats with HCM had higher concentrations of palmitic acid (P = 0.01), docosahexanoic acid (DHA; P = 0.001) and total n-3 fatty acids (P = 0.03), and lower concentrations of linoleic acid (P = 0.03). Among cats with HCM, there were no differences in plasma fatty acid concentrations, and no association between left atrial dimension and fatty acid concentrations. Cats with HCM have some alterations in plasma fatty acids compared with healthy controls. Given the higher plasma concentrations of DHA, DHA supplementation is unlikely to have benefits in terms of correcting a deficiency; however, other effects of DHA or of supplementation of EPA warrant further investigation.

Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation.

All seven lysine residues in ubiquitin contribute to the synthesis of polyubiquitin chains on protein substrates. Whereas K48-linked chains are well established as mediators of proteasomal degradation, and K63-linked chains act in nonproteolytic events, the roles of unconventional polyubiquitin chains linked through K6, K11, K27, K29, or K33 are not well understood. Here, we report that the unconventional linkages are abundant in vivo and that all non-K63 linkages may target proteins for degradation. Ubiquitin with K48 as the single lysine cannot support yeast viability, and different linkages have partially redundant functions. By profiling both the entire yeast proteome and ubiquitinated proteins in wild-type and ubiquitin K11R mutant strains using mass spectrometry, we identified K11 linkage-specific substrates, including Ubc6, a ubiquitin-conjugating enzyme involved in endoplasmic reticulum-associated degradation (ERAD). Ubc6 primarily synthesizes K11-linked chains, and K11 linkages function in the ERAD pathway. Thus, unconventional polyubiquitin chains are critical for ubiquitin-proteasome system function.

Omega-3 fatty acids in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Omega-3 fatty acids have been shown to reduce arrhythmia in animal models and people. These effects have not been studied in dogs with spontaneously occurring arrhythmia. HYPOTHESIS: Fish oil will reduce the frequency of ventricular arrhythmia in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Twenty-four Boxers with ARVC were included in this study. METHODS: Asymptomatic Boxers not receiving antiarrhythmic medications were evaluated with echocardiogram and electrocardiogram. Dogs with at least 1 ventricular premature contraction (VPC) received 24-hour ambulatory electrocardiography (AECG) recordings. Dogs with > 95 VPCs in 24 hours were randomized to 1 of 3 treatments: (1) Fish oil, 2 g; (2) Flax oil, 2 g; or (3) sunflower oil, 2 g (Control group), for 6 weeks. Investigators and owners were blinded to the treatment groups. All baseline measurements were repeated after the 6-week supplementation. RESULTS: There were no differences at baseline for age, sex, blood pressure, weight, echocardiographic measurements, or VPCs. Median number of VPCs in 24 hours for all dogs was 543 (range, 96-40,063) at baseline and 193 (range, 6-14,825) after 6 weeks of supplementation. VPCs/24 h were reduced for the Fish oil group (baseline median = 397 [range, 249-10,587]; 6-week median = 162 [range, 16-3,781]; P = .02), but not for the Flax oil (P = .58) or Control (P = .48) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that fish oil, but not flax oil, supplementation for 6 weeks reduces arrhythmia in Boxers with ARVC and that it could be useful in treating this common disease. Further studies are needed to determine optimal dose and duration of treatment.

Dietary patterns of cats with cardiac disease.

OBJECTIVE: To determine nutrient intake and dietary patterns in cats with cardiac disease. DESIGN: Prospective study. ANIMALS: 95 cats with congenital cardiac disease or primary cardiomyopathy. PROCEDURES: Owners completed a standardized telephone questionnaire regarding their cat's diet and a 24-hour food recall to determine daily intake of calories, fat, protein, sodium, magnesium, and potassium. RESULTS: Of the 95 cats, 18 (19%) had a history of congestive heart failure and 73 (77%) had no clinical signs of cardiac disease. Fifty-five percent (52/95) of cats had concurrent disease. Inappetance was reported in 38% (36/95) of all cats and in 72% (68/95) of cats with a history of congestive heart failure. Most (57% [54/95]) cats received treats or table scraps on a regular basis. Approximately half the cats were receiving orally administered medications, supplements, or both. Only 34% (32/68) of owners used food to administer medications to cats. Cats consumed more than the Association of American Feed Control Officials (AAFCO) minimums for protein, sodium, potassium, and magnesium, and nearly all cats consumed more than the AAFCO minimum for fat. Daily nutrient intake was variable for all of the nutrients assessed. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary intake in cats with cardiac disease was variable, but results for dietary supplement use, food use for medication administration, and treat feeding were different from those found in a similar study of dogs with cardiac disease. This information may be useful for treating and designing nutritional studies for cats with cardiac disease.

Effects of dietary modification in dogs with early chronic valvular disease.

BACKGROUND: The potential benefits of nutritional modification in early canine cardiac disease are not known. HYPOTHESIS: We hypothesized that echocardiographic, neuroendocrine, and nutritional variables will differ between dogs with asymptomatic chronic valvular disease (CVD) and healthy controls, and that a moderately reduced sodium diet enriched with antioxidants, n-3 fatty acids, taurine, carnitine, and arginine will alter these variables in dogs with CVD. METHODS: Echocardiography was performed and blood was collected. After baseline comparison with healthy controls, all dogs with CVD were fed a low-sodium run-in diet for 4 weeks, reevaluated, and then randomized to receive either the cardiac diet or a placebo diet for 4 weeks. RESULTS: At baseline, dogs with CVD (n = 29) had significantly lower circulating sodium, chloride, arginine, and methionine concentrations and higher plasma concentrations of atrial natriuretic peptide compared to healthy controls. In dogs with CVD, plasma aldosterone concentration and heart rate increased significantly after 4 weeks of eating the run-in diet. The cardiac diet group (n = 14) had larger increases in levels of cholesterol (P = .001), triglycerides (P = .02), eicosapentaenoic acid (P < .001), docosahexaenoic acid (P < .001), total omega-3 fatty acids (P < .001), vitamin C (P = 0.04), alpha-tocopherol (P < .001), and gamma-tocopherol (P < .001) compared to the placebo diet group (n = 15). The cardiac diet group also had larger reductions in maximal left-atrial dimension (P = .003), left-ventricular internal dimension in diastole (P = .03), and weight-based maximal left-atrial dimension (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Observed changes in both blood variables and echocardiographic measurements warrant additional studies on dietary modifications in dogs with early CVD.

A one year follow-up of the multimodal treatment for chronic pain.

Twenty-three outpatients with chronic pain began a 3-part treatment package designed to provide symptom control, stimulus control and social system modification. Fourteen patients completed the full course of therapy. The remaining 9 patients were designated as partial completers. A mean of 22.9 weekly hour long therapy sessions resulted in statistically significant decreases in pain, depression, anxiety and medication intake. These improvements were maintained at 1 year follow-up. This study is consistent with the notion that chronic pain is maintained by a combination of inter- and intrapersonal factors. A controlled comparison of this treatment program with other treatments for chronic pain is indicated.

A pilot study of the treatment of outpatients with chronic pain: symptom control, stimulus control and social system intervention.

Of 6 outpatients with chronic pain, 5 completed therapy based on a 3-part treatment package designed to provide symptom control, stimulus control and social system modification. Each of the components of the treatment package resulted in therapeutic change. A mean of 35.8 weekly hour long therapy sessions resulted in statistically significant decreases in pain, hopelessness, depression and analgesic medication intake. Generally, these improvements were maintained at 6 months and 1 year follow-up. This study is consistent with the notion that chronic pain is maintained by a combination of inter- and intrapersonal factors. A controlled comparison of this treatment program with other treatments for chronic pain is indicated.