Arrhythmias and transient changes in cardiac function after topical administration of one drop of phenylephrine 10% in an adult cat undergoing conjunctival graft

HistoryA 2-year-old, entire female, Somali cat weighing 3.8 kg was admitted for a conjunctival graft on the right eye, for treatment of an acute descemetocele. Medetomidine 4.2 μg kg^?1 and methadone 0.2 mg kg^?1 were administered by intramuscular injection as preanaesthetic medication. Anaesthesia was induced using diazepam 0.26 mg kg^?1 and propofol 4 mg kg^?1 administered by intravenous (IV) injection. Following endotracheal intubation, anaesthesia was maintained with isoflurane delivered in oxygen (1 L minute^?1) and nitrous oxide (2 L minute^?1) via a non-rebreathing system. Twenty minutes after induction of anaesthesia, one drop of a 10% phenylephrine hydrochloride solution was administered topically to the right eye.Physical examinationAfter phenylephrine administration, a decrease in heart rate (from 95 to 80 beats minute^?1) and an increase in arterial blood pressure occurred. The pulse then became difficult to palpate manually and multifocal ventricular premature contractions were observed on the electrocardiogram.ManagementNitrous oxide was discontinued and the isoflurane vaporizer setting was decreased from 1.5% to 0.5%. Lidocaine 1 mg kg^?1 IV was administered, this resulted in ventricular bigeminy. The quality of the femoral pulse improved and was regular in rhythm and character. Surgery was completed as fast as possible. The bigeminy progressively disappeared and before disconnecting the cat from the breathing system, there was a normal sinus rhythm with a heart rate of 85 beats minute^?1.Follow-upEchocardiography was performed during recovery and showed mitral and aortic valve insufficiency and dilation of the left ventricle, suggesting a reduction in systolic function. Echocardiography was repeated the following day and was normal.ConclusionsIn order to diminish the potential for cardiovascular sequelae associated with systemic absorption of ocular phenylephrine, less concentrated solutions, smaller drop size or different instillation techniques should be considered for topical use in small patients.     

Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping

A 9‐month‐old male Great Dane had progressive generalized nodular dermatopathy for several months. There were > 100 raised, alopecic, firm, painful nodules throughout the skin. Aspirates from several lesions yielded moderate numbers of irregularly round or polygonal to spindle‐shaped cells with mild to moderate anisocytosis and few inflammatory cells, and the cytologic interpretation was proliferation of mesenchymal or histiocytic cells. On histopathologic examination, nodules were composed of densely packed sheets of round to spindle‐shaped cells with mild anisokaryosis and low mitotic activity. Multifocal histiocytic sarcoma with a spindle‐cell pattern was diagnosed based on morphologic features and intense expression of CD18. Additional immunophenotypic analysis on frozen sections of tissue confirmed the diagnosis of histiocytic sarcoma; expression of CD18, CD45, CD1a, CD11b, and CD11c, limited expression of Thy‐1 (CD90) and CD80, and lack of expression of CD4, CD11d, and CD86 indicated that the cells were likely interstitial dendritic cells; a review of reactive and neoplastic dendritic cells is provided. Based on staging, internal organs were not affected. Sequential treatment with lomustine and doxorubicin failed to prevent progression of the cutaneous lesions, and the dog died 3 months after initial diagnosis. At necropsy, a focus of neoplastic cells was present in one lymph node, but except for skin other organs were not involved. The clinical presentation of histiocytic sarcoma may be unusual, and neoplastic cells may lack overt features of malignancy on cytologic and histopathologic examination. In some instances, immunophenotyping is required to differentiate histiocytic sarcoma from other histiocytic disorders.     

Exfoliative cutaneous lupus erythematosus in German shorthaired pointer dogs: disease development,progression and evaluation of three immunomodulatory drugs (ciclosporin,hydroxychloroquine, and adalimumab) in a controlled environment

Six German shorthaired pointer dogs (two females, four males) with exfoliative cutaneous lupus erythematosus (ECLE) were studied in a controlled setting until disease progression necessitated euthanasia. During investigations into the heredity of disease, five dogs received immunomodulatory drugs to alleviate clinical signs (lameness, erythema, scaling, erosions/ulcers). One dog served as a control and received only baths and oral fatty acids. Four dogs received ciclosporin (5–10 mg/kg once daily) for 4.5 months to 2 years. Ciclosporin decreased erythema and arthralgia, but did not halt worsening of lesions. Three dogs received hydroxychloroquine (5–10 mg/kg once daily) for 8 weeks, 7 months, and 9 months, respectively, with no side effects. Hydroxychloroquine appeared to slow clinical progression in two dogs on extended treatment and normalized globulin levels in all three dogs while receiving the drug. Four dogs, including the control dog, were euthanized between 1 and 4.5 years of age. Two remaining male dogs received a tumour necrosis factor (TNF)‐α antagonist, adalimumab, at 0.5 mg/kg every 2 weeks for 8 weeks then weekly for 8 weeks. Serum TNF‐α levels were not significantly altered nor were quantifiable changes seen in skin lesions or lameness. Subsequently, the dogs were maintained on hydroxychloroquine for another year. This is the first study to evaluate the use of a TNF‐α inhibitor for canine lupus and the first to address the safety of long‐term administration of hydroxychloroquine, albeit in a small number of dogs. The study documents the progression of ECLE and generally poor response to therapy.     

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs

Objective

To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs.

The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6

TLR2 recognises bacterial lipopeptides and lipoteichoic acid, and forms heterodimers with TLR1 or TLR6. TLR2 is relatively well characterised in mice and humans, with published crystal structures of human TLR2/1/Pam3CSK4 and murine TLR2/6/Pam2CSK4. Equine TLR4 is activated by a different panel of ligands to human and murine TLR4, but less is known about species differences at TLR2. We therefore cloned equine TLR2, TLR1 and TLR6, which showed over 80% sequence identity with these receptors from other mammals, and performed a structure-function analysis. TLR2/1 and TLR2/6 from both horses and humans dose-dependently responded to lipoteichoic acid from Staphylococcus aureus, with no significant species difference in EC50 at either receptor pair. The EC50 of Pam2CSK4 was the same for equine and human TLR2/6, indicating amino acid differences between the two species’ TLRs do not significantly affect ligand recognition. Species differences were seen between the responses to Pam2CSK4 and Pam3CSK4 at TLR2/1. Human TLR2/1, as expected, responded to Pam3CSK4 with greater potency and efficacy than Pam2CSK4. At equine TLR2/1, however, Pam3CSK4 was less potent than Pam2CSK4, with both ligands having similar efficacies. Molecular modelling indicates that the majority of non-conserved ligand-interacting residues are at the periphery of the TLR2 binding pocket and in the ligand peptide-interacting regions, which may cause subtle effects on ligand positioning. These results suggest that there are potentially important species differences in recognition of lipopeptides by TLR2/1, which may affect how the horse deals with bacterial infections.