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.     

Controlled Cross Circulation in Dogs: Effects on Donor Hemodynamics

Controlled cross circulation (CCC) was performed in six pairs of dogs for 45 minutes with aortic cross clamping and cardioplegia. Data were collected in donor dogs at 10 minute intervals three times before, three times during, and three times after CCC and included arterial blood pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI), heart rate (HR), blood gas analysis, temperature, maximum rate of rise of left ventricular pressure dP/dt max/End diastolic volume (EDV), blood volume (BV), complete blood count (CBC) and activated clotting times (ACT). Pulse pressure (PP), systemic vascular resistance (SVR), oxygen delivery (Do₂), and left ventricular cardiac work (LVCW) were calculated. Arterial blood pressure, CVP, blood gas analysis, temperature, BV, CBC, and ACT were measured in recipient dogs. During CCC, donor hemodynamic changes resembled those observed in models of acute onset arteriovenous fistulas. Insidious BV shifts can occur despite the use of occlusive roller pumps. After CCC, donor hemodynamics resembled acute blood loss, characterized by decreases in mean arterial pressure (MAP), CVP, PCWP, and CI, and increases in SVR and dP/dt max/EDV. These changes were probably caused by pump imbalance and BV shift to the recipient dog.     

木豆杂种优势利用研究进展

自1974年发现木豆雄性不育株以来,国际上不断对木豆核雄性不育(GMS)和核质互作雄性不育(CGMS)基因及其种质资源进行研究和挖掘,最终实现了木豆杂种优势的成功利用。本文系统总结了过去30多年来,国际上木豆杂种优势机理、表现及授粉方式等基础研究,GMS、CGMS不育系及其配套制种体系研究,杂种优势强度研究,以及木豆杂交种生产技术研究进展。提出了木豆杂种优势利用的具体研究方向和展望。     

Systemic and Local Effects Associated With Long-Term Epidural Catheterization and Morphine-Detomidine Administration in Horses

Objective — The purpose of this study was to determine the systemic and local effects associated with long-term epidural catheterization and epidural morphine-detomidine administration in horses. Study Design — Development of systemic or local effects was assessed by placing caudal epidural catheters in study horses and administering injections through the catheters every 12 hours for 14 days. Animals — Ten horses with epidural catheters that received daily injections; six uncatheterized horses presented for euthanasia. Methods — Horses received either 0.2 mg/kg morphine sulfate and 30 μg/kg detomidine hydrochloride or an equivalent volume of physiologic saline solution through epidural catheters. Systemic effects were compared between control and treatment horses by measuring physical parameters and hay and water consumption, as well as by evaluating major organs after euthanasia. Local effects were studied by examining cerebrospinal fluid and by grading representative samples of the spinal cord and surrounding tissues histologically for inflammation and fibrosis. Local effects were compared between control and treatment horses, as well as between catheter-ized (control plus treatment) horses and uncatheterized horses. Results — No significant difference was identified in daily variables or hay and water consumption between control and treatment horses. No growth was obtained from cerebrospinal fluid cultures. No significant difference in cerebrospinal fluid values or spinal tissue inflammation or fibrosis grades was shown between control and treatment horses. However, when compared with uncatheterized horses, cerebrospinal fluid red blood cell values were marginally higher and protein concentrations were significantly higher in the catheterized group. Lumbosacral and sacral spinal tissue segment inflammation grades, and sacral segment fibrosis grades were significantly higher in catheterized horses. Conclusions — Long-term epidural administration of a morphine-detomidine combination is not associated with apparent adverse systemic effects in horses. Localized inflammation and fibrosis seem to be catheter-related. Clinical Relevance — Potential systemic and local effects are important considerations with long-term administration of a morphine-detomidine combination through indwelling epidural catheters for alleviation of chronic musculoskeletal pain in horses.     

The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises

The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20 degrees C and the other at 30 degrees C. The mean (+/- SD) residence time for amikacin in the 30 degrees C tortoises was 22.67 +/- 0.50 h; significantly (P less than 0.05) less than those held at 20 degrees C (41.83 +/- 3.23 h). There was no significant difference (P greater than 0.05) in the steady-state volume of distribution (Vd(ss] between the tortoises held at 30 degrees C (0.241 +/- 0.520 l/kg) and those held at 20 degrees C (0.221 +/- 0.019 l/kg). The clearance rate was faster (P less than 0.05) in the warmer tortoises (10.65 +/- 2.42 ml/min/kg at 30 degrees C compared to 5.27 +/- 0.152 ml/min/kg at 20 degrees C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30 degrees C is 5 mg/kg given i.m. every 48 h.     

Mid‐gestation pregnancy is not disrupted by a 5‐day gastrointestinal mucosal cytoprotectant oral regimen of misoprostol

Reasons for performing study: To investigate effects of a 5‐day oral misoprostol regimen recommended for use in horses as a gastrointestinal mucosal cytoprotectant during colic on mid‐gestation pregnancies. Objectives: To monitor cervical tone, ultrasonographic characteristics of the uterus, cervix and conceptus, as well as serum progesterone and oestrone sulphate concentrations, and observations of general health, behaviour and comfort of mid‐gestation mares given a 5‐day course of misoprostol or control treatment. Methods: Eleven light horse and pony mares with known breeding dates were administered 5 µg/kg bwt misoprostol orally, twice daily for 5 days. General health and pregnancy status were monitored daily during treatment via general physical examination, as well as palpation and ultrasonography per rectum of the uterus, cervix and conceptus. Jugular serum was obtained during and for 5 days following treatment for assay of progesterone and oestrone sulphate concentrations. Additionally, daily 12 h video samples of the mares were obtained to evaluate behaviour and comfort. Results: All findings, including cervical tone, ultrasonographic characteristics of the uterus, cervix and conceptus, as well as progesterone and oestrone sulphate concentrations, and observations of general health, behaviour and comfort, were similar during misoprostol and control treatment. Conclusions: Treatment of pregnant mares with a gastrointestinal mucosal cytoprotectant regimen of oral misoprostol for 5 days did not disrupt pregnancy, nor adversely affect the general health and comfort of these mares. Additional investigation of treatment at earlier and later stages of gestation, for longer‐term treatment, as well as evaluating neonates for developmental disturbances, would add further information on safety of misoprostol during gestation. Potential relevance: These results provide some assurance of safety of a 5‐day gastrointestinal mucosal cytopretectant regimen of oral misprostol in mid‐gestation pregnant mares.     

Inclusion body disease in two captive Australian pythons (Morelia spilota variegata and Morelia spilota spilota)

Two captive Australian pythons, one carpet and one diamond python, presented with signs of central nervous system dysfunction. The carpet python was agitated. Its head was tilting and it was incoordinated and had convulsions. It was treated with antibiotics and anthelmintics but was eventually euthanased after failing to respond to therapy. The diamond python had flaccid paralysis of the caudal half. It was not treated and became disoriented and died. Hepatocytes from both pythons contained irregular 2 to 10 m m eosinophilic intracytoplasmic inclusion bodies. The brain of the diamond python was not available for examination. Occasional neurones in the carpet python brain contained similar inclusion bodies and other changes suggestive of viral infection. The clinical signs and histopathological findings in both pythons were consistent with boid inclusion body disease.