Objectives-To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Animals-5 healthy horses. Procedures-In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. Results-In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microgram/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microgram/mL and 1.91 +/- 0.50 microgram/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microgram/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. Conclusions and Clinical Relevance-Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.

Objective-To determine the effects of stress in cats with feline idiopathic cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress and after environmental enrichment. Design-Prospective study. Animals-13 cats with FIC and 12 healthy cats. Procedure-Cats subjected to an acute-onset moderate stressor for 8 days received IV injections of fluorescein. Serum fluorescein concentrations were determined and compared with those of controls to evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine concentrations were analyzed in a subset of cats. After 8 days of moderate stress, cats were moved to an enriched environment, and tests were repeated after 21 days. Results-Serum fluorescein concentrations were significantly higher in cats with FIC at all time points. In the cats in which plasma catecholamine concentrations were determined, concentrations of dihydroxyphenylalanine, norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with FIC at all time points, whereas no differences in urine C:Cr ratio between groups were observed. Conclusion and Clinical Relevance-Cats with FIC appeared to have altered bladder permeability, most notably during the period of initial stress. The increase in plasma dihydroxyphenylalanine concentration suggests that there may be stress-induced increase in the activity of tyrosine hydroxylase, which catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no effects of stress on C:Cr ratios were observed, which suggests there was dissociation between the sympathetic nervous system and HPA-axis responses to stress.