A randomized cross-over trial assessing salivary and urinary cortisol concentrations after alfaxalone and propofol administration in healthy cats.

The aim of this study was to assess the effects of commonly used anaesthetics alfaxalone and propofol on salivary and urinary cortisol in healthy cats. Fifteen male castrated research-purposed cats received randomly intravenous continuous rate infusions of 8 mg/kg/h of alfaxalone, 12 mg/kg/h of propofol and 2 ml/kg/h of Lactated Ringer's solution for 30 min, with intervals of 6 days between treatments. Saliva samples were collected for 24 h before each infusion and for 24 h from the start of each infusion. Urine was collected as single pooled samples over each 24 h period. Mean integrated saliva cortisol responses in cats treated with alfaxalone were greater than responses of cats treated with propofol (P = 0.034) and controls (P = 0.017). Integrated responses in cats treated with propofol did not differ from controls. The mean urinary cortisol/creatinine ratio (UCCR) was higher on the day of treatment than the day before treatment in cats treated with alfaxalone (P < 0.0001) and in cats treated with propofol (P = 0.0168) and did not differ between days in cats treated with lactated Ringer's solution. The mean UCCR was higher in cats treated with alfaxalone than in cats treated with lactated Ringer's solution (P = 0.0020) on the day of treatment. Mean total urinary cortisol over 24 h was greater in cats treated with alfaxalone than controls (P = 0.0267). In conclusion, alfaxalone increased short-term salivary and urinary cortisol concentrations in healthy cats as compared to propofol and a control group of non-anesthetised cats.

The effect of the sodium-glucose cotransporter type-2 inhibitor dapagliflozin on glomerular filtration rate in healthy cats.

Sodium-glucose cotransporter type-2 inhibitors (SGLT2is) reduce glomerular hyperfiltration in diabetic people with early diabetic nephropathy. The objective of this report was to assess changes in glomerular filtration rate in healthy cats after treatment with a SGLT2i. Eight healthy research adult castrated male cats were used in a randomized, controlled, cross-over study design. We induced isolated renal tubular glucosuria by dosing cats with the SGLT2i dapagliflozin. The cats received by mouth 10 mg dapagliflozin or control every 24 h in each of the 4, 5-d trial periods that were separated by a 7-d washout period. We assessed glomerular filtration rate (iohexol clearance method), serum urea, creatinine, symmetric dimethylarginine, and 24-h sodium and chloride urinary excretion on the fifth day of each trial period. We analyzed the data with a mixed linear model that included the fixed effects of treatment (treated and control) and trial period, and the random effect of the cat. Compared with controls, cats treated with dapagliflozin had a significant increase in mean (±SE) glomerular filtration rate (3.1 ± 0.2 vs 2.5 ± 0.2 mL/kg/min; P = 0.01), whereas there were no significant differences in serum urea, creatinine and symmetric dimethylarginine, and 24-h urine sodium and chloride excretion. We propose that dapagliflozin-mediated delivery of sodium and glucose distal from the proximal convoluted tubule induced compensatory increased sodium absorption at the thick ascending loop of Henle that resulted in decreased sodium delivery to the distal tubule leading to tubuloglomerular feedback-mediated glomerular hyperfiltration. Future studies should determine if SGLT2is' renoprotective effect in people can be enhanced with the addition of a Na+-K+-Cl- diuretic and whether dapagliflozin will be useful in mitigating proteinuria and hypertension that follow glomerular hyperfiltration in diabetic companion animals in a similar mechanism as in people.

Biological Variability in Serum Cortisol Concentration Post-adrenocorticotropic Hormone Stimulation in Healthy Dogs.

BACKGROUND: The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. HYPOTHESIS/OBJECTIVES: To report the components of biological and analytical variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in healthy dogs. ANIMALS: Fourteen healthy harrier hound dogs. METHODS: The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (CD ), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated. RESULTS: The IoI was equal to 1.1 and the CD was 3.3 µg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 µg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 µg/dL [318 ± 65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. CONCLUSIONS AND CLINICAL IMPORTANCE: False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large CD emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC.

Seasonal and age effects on energy requirements in domestic short-hair cats (Felis catus) in a temperate environment.

There is little information known about the energy requirements of cats in temperature climates. Energy requirement of domestic short-haired cats was determined using three groups of mixed gender - old kept outside (approximately 9.9 years of age; 4.8 kg; n = 9), young kept outside (approximately 3.1 years of age; 3.9 kg; n = 8) or young kept inside (approximately 3.1 years of age; 3.9 kg; n = 8). Cats were housed individually for 5 weeks during summer (18.5 ± 0.5 °C) and winter (8.5 ± 0.4 °C) and were fed a commercially available maintenance diet ad libitum. In both periods, energy expenditure was determined from the rates of (2) H and (18) O elimination for blood H2 O over a 12 day period, from a doubly labelled water bolus (2) H2 O (0.7 g/kg BW) and H2 (18) O (0.13 g/kg BW) administered intravenously. During the summer period, macronutrient digestibility was determined. Older cats had a reduction (p < 0.05) in apparent digestibility of dry matter (approximately 9%), energy (approximately 8%) and protein (6%). There was a significant effect of age and season on energy intake and energy expenditure. While lean mass was affected by age and season, there was no effect of age or season on energy expenditure when expressed as a proportion of lean mass. Possible seasonal differences in nutrient digestibility may explain these results.

Testosterone increases urinary free felinine, N-acetylfelinine and methylbutanolglutathione excretion in cats (Felis catus).

Two days after castration, urinary free felinine plus N-acetylfelinine decreased 24% in male cats, but, by day 5, the concentration had not decreased to that routinely found in males that have been castrated for several months. In a second experiment, three groups of castrated adult male cats received different subcutaneous injections: control (carrier), testosterone, testosterone plus estradiol. A fourth group of intact adult female cats received a testosterone injection. Urine was collected and analysed for free felinine, N-acetylfelinine and 3-methylbutanolglutathione. Baseline blood testosterone and estradiol concentrations were low during the pre-period, but increased sharply after hormone injections. The concentration of all three urinary metabolites increased as a result of testosterone injections with estradiol not modulating the effect. The effect of testosterone was not gender dependent. The concentration of free felinine, N-acetylfelinine and 3-methylbutanolglutathione in the urine remained low in the placebo control group throughout the study. The relative molar contribution of free felinine to the total amount of felinine containing compounds increased due to testosterone treatment, while the contribution of 3-methylbutanolglutathione and N-acetylfelinine decreased. Testosterone increases free felinine, N-acetylfelinine and 3-methylbutanolglutathione excretion in castrated adult male and intact female cats, whereas estradiol does not modulate this effect.