A Review of Relevant Therapeutic Targets for the Management of Congestive Heart Failure in Dogs: Present and Future Directions

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses

BackgroundPain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses.MethodsPBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites.ResultsNon-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46–7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb.ConclusionPBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation

Clinical features of cats with aqueous tear deficiency: a retrospective case series of 10 patients (17 eyes)

Objectives The aim of this study was to describe the clinical findings, diagnostic test results and response to therapy of cats with Schirmer tear test 1 (STT-1) values below the reference interval. Methods The medical records of three institutions were searched for cats with ocular surface disease and STT-1 values/min, confirmed at two or more separate visits. Results Ten cats (17 eyes) were included. The mean ± SD (range) age and STT-1 values in affected eye(s) were 6.1 ± 5.7 (0.2–16) years and 2.4 ± 3.1 (0–8) mm/min, respectively. Concurrent ocular surface disease was bilateral in 5/10 cats. Clinical signs included conjunctivitis (14/17 eyes), corneal ulceration (6/17 eyes), non-ulcerative keratitis (4/17 eyes), symblepharon (4/17 eyes), eosinophilic keratitis (3/17 eyes), corneal sequestrum (3/17 eyes), corneal fibrosis (2/17 eyes) and meibomitis (2/17 eyes). Management included topically applied lacrimomimetics, antiviral drugs, corticosteroids or immunomodulatory drugs; orally administered famciclovir; or surgical procedures, in various combinations. Response to therapy (defined as an increase in STT-1 value of ⩾5 mm/min) was transient (seen at a single reassessment) in 65% of eyes and sustained (seen at ⩾2 consecutive reassessments) in 18% of eyes. Conclusions and relevance Clinical features seen in cats with low STT-1 values are described, although the association between aqueous deficiency and the reported ocular changes is unknown at this time. We encourage clinicians to assess the tear film in cats with ocular surface disease, and initiate therapy with lacrimomimetics if STT-1 values are repeatedly below normal. Such information will further define aqueous tear deficiency in cats, providing a better understanding of disease prevalence, pathogenesis and treatment