Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs

Brown, S.A., Jacobson, J.D., Hartsfield, S.M. Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs. J. vet. Pharmacol. Therap. 16 , 419–425. Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2–33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t_½α of 1.8 min and t_½β.p of 27.8 min after i.v. bolus, and t_½α f 1–35 min and t_½β of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 ± 244 ng/ml) than after i.v. bolus (888 ± 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29 800 ±6120 ng/h/ml) than after i.v. bolus (42 500 ± 8460 ng/h/ml, P < 0.05), resulting in a larger Cl_B after i.v. infusion (17.4 ± 4.00 ml/min/kg than after i.v. bolus (12.1 ± 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.     

Quantitative analysis of canine plasma lipoproteins

A combined ultracentrifugationl/precipitation method for the measurement of lipoprotein cholesterol concentrations was developed and validated for use with canine plasma. Very low density lipoproteins (VLDL) were isolated by flotation ultracentrifugation and low density lipoproteins (LDL) separated from high density lipoproteins (HDL) by precipitation with heparin-manganese chloride. Effective separation of these classes was confirmed by agarose gel electrophoresis of native lipoproteins and by sodium dodecyl sulphate polyacrylamide gel electrophoresis of their apolipoprotein distributions. There was trace contamination of the LDL precipitate with HDL, but this represented less than 4 and 9 per cent of the total plasma HDL in normo- and hypercholesterolaemic dogs, respectively. The intra-assay and interassay coefficients of variation for LDL- and HDL-cholesterol concentrations were between 3·3 and 6·9 per cent, and 7·2 and 9·0 per cent, respectively, for plasma cholesterol concentrations between 2·67 and 8·14 mmoll/litre. The intra-assay coefficient of variation for VLDL-cholesterol was 53·8 and 18·4 per cent at plasma cholesterol concentrations of 2·67 and 8·14 mmol/litre, respectively. The interassay coefficient of variation for VLDL was 22·5 per cent. Storage of plasma at -20°C for between two and eight weeks did not affect VLDL-cholesterol concentrations, but led to an increase in LDL-cholesterol and a decrease in HDL-cholesterol concentrations of approximately 10 per cent. The method described is appropriate for the measurement of lipoprotein concentrations in plasma from normo- and hypercholesterolaemic dogs, but samples should not be subjected to prolonged storage before analysis.     

Radiographic interpretation of normal skeletal variations and pseudolesions in the equine foot.

Effective radiographic interpretation requires a veterinarian who is knowledgeable of equine limb anatomy and the various principles that affect the resulting image. The normal and its variations must be recognized and understood before the abnormal can be confidently identified as pathologic. Proper patient positioning and sound radiographic technique are mandatory if reliable diagnostic radiographs are to be produced. This review emphasizes equine foot radiographic variations of normal and pseudolesions that occur with commonly used radiographic views performed in equine practice.     

Oxalate Nephrosis and Renal Sclerosis After Renal Transplantation in a Cat

A 10-year-old castrated domestic shorthair cat received two renal allografts, 14 days apart, for the treatment of chronic renal failure. Oxalate nephrosis developed in both allografts, and they became nonfunctional. During the transplantation period, the cat was not exposed to exogenous sources of oxalate, and there was no evidence of primary type 2 hyperoxaluria before surgery. Urologic surgery, in particular renal transplantation, has been identified as a factor that can precipitate renal failure in human patients with decompensated renal function and hyperoxaluria. If hyperoxaluria was present before surgery in this cat, it was most likely caused by increased absorption or decreased metabolism of dietary oxalate.     

Nitrogen uptake by ryegrass from organic wastes applied to a sandy loam soil

Sandy‐textured Mediterranean soils are invariably depleted in organic matter and supply only small amounts of N to crops. To compensate for these deficiencies, we tested the N supply from six organic wastes applied to a Cambic Arenosol in pots growing ryegrass. The results showed that the behaviour of the wastes in supplying N to a ryegrass crop grown in this soil can be predicted by observing their performance in laboratory aerobic incubations. The N made available during these incubations fitted well to a one‐pool kinetic model.     

A novel approach to studying the effects of temperature on soil biogeochemistry using a thermal gradient bar

The temperature dependence of chemical reaction rates and microbial metabolism mean that temperature is a key factor regulating soil trace gas emissions and hydrochemistry. Here we evaluated a novel approach for studying the thermal response of soils, by examining the effects of temperature on gas emissions and hydrochemistry in (a) peat and (b) soil from a Sitka spruce plantation. A thermal gradient was applied along an aluminium bar, allowing soil to be incubated contemporaneously from 2 to 18 °C. The approach demonstrated clear differences in the biogeochemical responses of the two soil types to warming. The peat showed no significant emission of CH₄ at temperatures below 6 °C, while above 6 °C, a marked increase in the rate of release was apparent up to 15 °C (Q₁₀ = 2.5) with emissions being similar between 15 and 18 °C. Conversely, CH₄ emissions from the forest soil did not respond to warming. Nitrate availability in the peat decreased by 90% between 2 and 18 °C (P < 0.01), whereas concentrations in the forest soil did not respond. Sulphate availability in the peat decreased significantly with warming (60%, P < 0.01), while the forest soil showed the opposite response (a 30% increase, P < 0.01). Conventionally, thermal responses are studied by incubating individual soil samples at different temperatures, involving lengthy preparation and facilities to incubate samples at different temperatures simultaneously. Data collected on a given thermal response is usually limited and thus interpolated or extrapolated. The thermal gradient method overcomes these problems, is simple and flexible, and can be adapted for a wide range of sample types (not confined to soil). Such apparatus may prove useful in the optimization of management practices to mitigate the effects of climate change, as thermal responses will differ depending on land use and soil type.