The fat-1 transgene in mice increases antioxidant potential, reduces pro-inflammatory cytokine levels, and enhances PPARγ and SIRT-1 expression on a calorie restricted diet

18 Objective To evaluate the cardiopulmonary and sedative effects of xylazine alone or in 19 combination with methadone, morphine or tramadol in sheep. 20 Study design Experimental, prospective, crossover, randomized, blinded study. 21 Animals Six Santa Inês breed sheep (females) aged 12 ± 8 months and weighing 39.5 ± 7.4 kg. 22 Methods Sheep were sedated with each of four treatments in a randomized, crossover design, 23 with a minimum washout period of 7 days between treatments. Treatments were: X [xylazine 24 (0.1 mg kg)]; XM [xylazine (0.1 mg kg) and methadone (0.5 mg kg)]; XMO [xylazine 25 (0.1 mg kg) and morphine (0.5 mg kg)], and XT [xylazine (0.1 mg kg) and tramadol 26 (5 mg kg)]. Each drug combination was mixed in the syringe and injected intravenously. 27 Sedation, heart rate (HR), mean arterial blood pressure (MAP), rectal temperature (RT °C), 28 respiratory rate (fR), arterial blood gases and electrolytes were measured before drug 29 administration (T0) and then at 15 minute intervals for 120 minutes (T15–T120). 30 Results Heart rate significantly decreased in all treatments compared with T0. PaCO2 values in 31 XM and XMO were higher at all time points compared with T0. In treatments X and XM, pH, 32 bicarbonate (HCO3) and base excess were increased at all time points compared with T0. PaO2 33 was significantly decreased at T15–T75 in XM, at all time points in XMO, and at T15 and T30 in 34 XT. Sedation at T15 and T30 in XM and XMO was greater than in the other treatments. 35 Conclusions and clinical relevance The combinations of methadone, morphine or tramadol 36 with xylazine resulted in cardiopulmonary changes similar to those induced by xylazine alone in 37 sheep. The combinations provided better sedation, principally at 15 minutes and 30 minutes 38 following administration. 39 40