Endothelin-1 concentrations in bronchoalveolar lavage fluid of cats with experimentally induced asthma

Background There is a need for biomarkers for diagnosis, therapeutic monitoring, and prognosis for asthma in cats. Endothelin‐1 (ET‐1) is implicated in the pathogenesis of inflammatory airway diseases in other species but not the cat. Objective To conduct a prospective experimental study to show that experimentally asthmatic cats, but not control cats without airway inflammation, would have increased concentrations of ET in BALF. Animals Eleven healthy, adult research cats. Methods Prospective experimental study. Six healthy cats without airway inflammation were used as controls. Asthma was induced using Bermuda grass allergen (BGA) in 5 cats. Collection of BALF for total nucleated cell and differential counts was performed. The concentration of ET‐1 in cell‐free BALF samples was determined. Data were analyzed using a Mann–Whitney U‐test with P < .05 considered significant. Results The median [range] BALF total cell numbers, eosinophil numbers, and eosinophil percentages were significantly higher in the cats following experimental induction of asthma (1,870 cells/μL [1,450–3,440], 711 cells/μL [356–1,686] and 38% [20–49]) compared to baseline control parameters (462 cells/μL [239–780], 18 cells/μL [18–62] and 3.5% [0–8]) (P < .01). The median [range] BALF ET concentration was also significantly higher after induction of asthma (1.393 fmol/mL[0.977–2.247]) compared to healthy control cats (0.83250 fmol/mL [0.625–1.038]) (P = .012). Conclusions and Clinical Importance This study suggests that BAL ET‐1 concentration can be used to differentiate normal cats from those with experimentally induced asthma. If the same holds true for cats with naturally developing asthma, BAL ET‐1 may prove a useful diagnostic biomarker for asthma

Cysteinyl-leukotriene receptor antagonism blunts the acute hypotensive response to endotoxin in cats

This study evaluated the effects of a cysteinyl-leukotriene-1 (cys-LT-1) receptor antagonist, zarfirlukast, during feline endotoxemia. Six adult, sexually intact male cats received either placebo or zarfirlukast (10 mg, PO) and endotoxin (2 μg/kg/h q 6 h) in a cross-over design. Rectal temperature, heart rate, systolic arterial blood pressure, plasma tumor necrosis factor (TNF) activity, interleukin (IL)-6 concentration and urine cys-LT to creatinine ratio were evaluated. The rectal temperature, plasma TNF activity and IL-6 concentrations were significantly higher and systolic arterial blood pressure and heart rate significantly lower after endotoxin infusion. Cats treated with zafirlukast had a significantly higher blood pressure at 4 h (P=0.002) compared to placebo. Urine cys-LT to creatinine ratio was significantly greater in the cats treated with zafirlukast compared to placebo (P=0.02). Zafirlukast administration ameliorated the acute hypotensive response to endotoxin in cats, but failed to significantly alter rectal temperature, heart rate or production of TNF and IL-6

Evaluation of the anti-endotoxin effects of polymyxin B in a feline model of endotoxemia

Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. We investigated the anti-endotoxin effects of polymyxin B (PMB) in a blinded, placebo controlled fashion, both ex vivo in a feline whole blood culture system and in vivo, using a low-dose endotoxin infusion in cats. Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Ex vivo, PMB significantly decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from whole blood. PMB (1 mg/kg over 30 min) demonstrated anti-endotoxin effects in vivo, including decreased peak plasma TNF activity (P<0.001) and increased white blood cell count (P=0.019), with no adverse effects. Given the apparent safety and anti-endotoxin effects of PMB in this endotoxemia model, a carefully designed, randomized, blinded, placebo controlled clinical trial evaluating the use of PMB in naturally occurring Gram-negative feline sepsis should be considered