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1.

Objective

To characterize the cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous (IV) administration in cats.

Study design

Prospective Latin square experimental study.

Animals

Six healthy adult purpose-bred cats.

Methods

Cats were anesthetized with desflurane in oxygen for instrumentation with a carotid artery catheter and a thermodilution catheter in the pulmonary artery. One hour after discontinuation of desflurane, cats were administered dexmedetomidine (25 μg kg–1), MK-467 (600 μg kg–1), or dexmedetomidine (25 μg kg–1) and MK-467 (600 μg kg–1). All treatments were administered IV as a bolus. Cardiovascular variables were measured prior to drug administration and for 8 hours thereafter. Only data from the dexmedetomidine and dexmedetomidine–MK-467 treatments were analyzed.

Results

Dexmedetomidine produced significant decreases in heart rate, cardiac index and right ventricular stroke work index, and significant increases in arterial blood pressure, central venous pressure, pulmonary artery pressure and systemic vascular resistance index. Dexmedetomidine combined with MK-467 resulted in significant but transient decrease in blood pressure and right ventricular stroke work index.

Conclusion and clinical relevance

Following IV co-administration, MK-467 effectively attenuated dexmedetomidine-induced cardiovascular effects in cats. The drug combination resulted in transient reduction in arterial blood pressure, without causing hypotension.  相似文献   

2.
3.

Objective

The evaluation of alfaxalone as a premedication agent and intravenous anaesthetic in pigs.

Study design

Prospective, clinical trial.

Animals

Nine healthy, 6–8-week-old female Landrace pigs weighing 22.2 ± 1.0 kg, undergoing epidural catheter placement.

Methods

All pigs were premedicated with 4 mg kg?1 alfaxalone, 40 μg kg?1 medetomidine and 0.4 mg kg?1 butorphanol administered in the cervical musculature. Sedation was subjectively scored by the same observer from 1 (no sedation) to 10 (profound sedation) prior to induction of anaesthesia with alfaxalone intravenously to effect. All pigs were maintained on alfaxalone infusions with the rate of administration adjusted to maintain appropriate anaesthetic depth. Quality of induction was scored from 1 (poor) to 3 (smooth) and basic cardiorespiratory variables were recorded every 5 minutes during anaesthesia. Results are reported as mean ± standard deviation or median (range) as appropriate.

Results

Sedation scores were 9 (7–10). Inductions were smooth in all pigs and cardiovascular variables remained within normal limits for the duration of anaesthesia. The induction dose of alfaxalone was 0.9 (0.0–2.3) mg kg?1. Three pigs did not require additional alfaxalone after premedication to facilitate intubation.

Conclusions and clinical relevance

Intramuscular alfaxalone in combination with medetomidine and butorphanol produced moderate to deep sedation in pigs. Alfaxalone produced satisfactory induction and maintenance of anaesthesia with minimal cardiovascular side effects. Appropriate monitoring of pigs premedicated with this protocol is required as some pigs may become anaesthetized after intramuscular administration of this combination of drugs.  相似文献   

4.

Objective

To compare the effects of two balanced anaesthetic protocols (isoflurane–dexmedetomidine versus medetomidine) on sedation, cardiopulmonary function and recovery in horses.

Study design

Prospective, blinded, randomized clinical study.

Animals

Sixty healthy adult warm blood horses undergoing elective surgery.

Methods

Thirty horses each were sedated with dexmedetomidine 3.5 μg kg?1 (group DEX) or medetomidine 7 μg kg?1 (group MED) intravenously. After assessing and supplementing sedation if necessary, anaesthesia was induced with ketamine/diazepam and maintained with isoflurane in oxygen/air and dexmedetomidine 1.75 μg kg?1 hour?1 or medetomidine 3.5 μg kg?1 hour?1. Ringer's lactate (7–10 mL kg?1 hour?1) and dobutamine were administered to maintain normotension. Controlled mechanical ventilation maintained end-tidal expired carbon dioxide pressures at 40–50 mmHg (5.3–6.7 kPa). Heart rate, invasive arterial blood pressure, inspired and expired gas composition and arterial blood gases were measured. Dexmedetomidine 1 μg kg?1 or medetomidine 2 μg kg?1 was administered for timed and scored recovery phase. Data were analysed using two-way repeated-measures analysis of variance and chi-square test. Significance was considered when p  0.05.

Results

In group DEX, significantly more horses (n = 18) did not fulfil the sedation criteria prior to induction and received one or more supplemental doses, whereas in group MED only two horses needed one additional bolus. Median (range) total sedation doses were dexmedetomidine 4 (4–9) μg kg?1 or medetomidine 7 (7–9) μg kg?1. During general anaesthesia, cardiopulmonary parameters did not differ significantly between groups. Recovery scores in group DEX were significantly better than in group MED.

Conclusions and clinical relevance

Horses administered dexmedetomidine required more than 50% of the medetomidine dose to reach equivalent sedation. During isoflurane anaesthesia, cardiopulmonary function was comparable between the two groups. Recovery scores following dexmedetomidine were better compared to medetomidine.  相似文献   

5.

Objective

To study the effects of MK-467, a peripheral α2-adrenoceptor antagonist, on sedation, heart rate and blood pressure after intramuscular (IM) coadministration with 25 μg kg?1 of dexmedetomidine in cats.

Study design

Prospective, randomized, controlled, blinded, cross-over, experimental study.

Animals

A total of eight healthy, adult, neutered male cats.

Methods

Cats were administered five IM treatments at least 2 weeks apart, consisting of dexmedetomidine 25 μg kg?1 (D25), MK-467 600 μg kg?1 (M600) and D25 combined with 300, 600 and 1200 μg kg?1 of MK-467 (D25M300, D25M600 and D25M1200, respectively). Heart rate and direct arterial blood pressure were recorded via telemetry and sedation assessed prior to treatments and at intervals for 8 hours thereafter.

Results

Heart rate decreased significantly after all treatments with dexmedetomidine and remained below baseline up to 240 (D25), 20 (D25M300) and 3 minutes (D25M600 and D25M1200). Mean arterial pressure (MAP) increased with D25, remained unchanged with M600 and decreased over time with all combination treatments. The highest and lowest MAP after each treatment were 168 ± 17 and 100 ± 14 (D25), 157 ± 18 and 79 ± 11 (D25M300), 153 ± 11 and 74 ± 10 (D25M600), 144 ± 12 and 69 ± 7 (D25M1200) and 136 ± 9 and 104 ± 13 mmHg (M600). All treatments with dexmedetomidine produced sedation although its duration was significantly reduced by the addition of MK-467.

Conclusions and clinical relevance

Dexmedetomidine induced bradycardia and hypertension, which were attenuated by all three doses of MK-467. The duration of sedation was reduced by MK-467. MK-467 may improve the cardiovascular tolerance of IM dexmedetomidine in cats.  相似文献   

6.

Objective

To characterize the hemodynamic effects of dexmedetomidine, with or without MK-467, following intramuscular (IM) administration in cats.

Study design

Randomized, crossover, experimental study.

Animals

Six healthy adult male castrated purpose-bred cats.

Methods

Cats were anesthetized with isoflurane in oxygen and instrumented. Cats were administered dexmedetomidine (25 μg kg?1), with (DM) or without (D) MK-467 (600 μg kg?1), IM in the epaxial muscles. Cardiovascular variables, respiratory variables, temperature, and arterial and mixed-venous pH, blood gases and electrolytes were measured prior to drug administration and at various time points for 6 hours thereafter, during anesthesia with isoflurane. Additional variables were calculated from the measurements, using standard equations. Results were analyzed with a two-way repeated-measures analysis of variance, followed by Dunnett’s and paired t tests where appropriate.

Results

Dexmedetomidine resulted in a significant decrease in cardiac index (CI) and significant increases in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). The addition of MK-467 failed to prevent most of the early cardiovascular effects of dexmedetomidine, but the duration of systemic vasoconstriction was shorter and CI did not decrease. The lowest and highest post-treatment values in each treatment were 0.1 ± 0.03 and 0.13 ± 0.03 L minute?1 BW?0.67 (D) versus 0.14 ± 0.01 and 0.19 ± 0.03 L minute?1 BW?0.67 (DM) for CI, 87 ± 13 and 181 ± 21 mmHg (D) versus 70 ± 11 and 153 ± 18 mmHg (DM) for MAP and 58,948 ± 17,754 and 119,432 ± 40,423 dynes second cm?5 BW?0.67 (D) versus 25,870 ± 3782 and 76,498 ± 17,258 dynes second cm?5 BW?0.67 (DM) for SVRI, respectively.

Conclusion and clinical relevance

IM coadministration of MK-467 and dexmedetomidine in isoflurane-anesthetized cats shortened dexmedetomidine-induced cardiovascular effects. This drug combination may be useful in cats in which longer-lasting hypertension and hemodynamic depression is of concern.  相似文献   

7.

Objective

To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.

Study design

Prospective randomized crossover experimental study.

Animals

A total of eight healthy adult male castrated cats aged 1–2 years.

Methods

Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data.

Results

A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM.

Conclusions and clinical relevance

MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.  相似文献   

8.
9.

Objective

To investigate whether an intravenous (IV) lidocaine bolus in calves premedicated with xylazine-butorphanol reduces the amount of ketamine required to allow endotracheal intubation.

Study design

Randomized, prospective clinical study.

Animals

In total, 41 calves scheduled for elective umbilical surgery.

Methods

Calves were randomly assigned to one of two groups (L: lidocaine or S: saline). The calves were administered xylazine (0.07 mg kg?1) and butorphanol (0.1 mg kg?1) intramuscularly and 10 minutes later lidocaine (2 mg kg?1; group L) or saline (group S) IV over 1 minute. After 2 minutes, ketamine (2.5 mg kg?1) was injected IV. If the depth of anaesthesia was insufficient for intubation, additional ketamine (1 mg kg?1) was administered every minute until intubation was successful. The amount of ketamine required for intubation, respiratory rate, pulse rate, arterial pressures, the depth of sedation and conditions of endotracheal intubation after induction of anaesthesia were compared between the two groups.

Results

The calves in group L were sedated more deeply than those in group S; however, neither the median (range) amount of ketamine required for intubation, 3.5 (2.5–4.5) mg kg?1 and 3.5 (2.5–3.5) mg kg?1, respectively, nor the induction quality differed significantly between the groups.

Conclusion and clinical relevance

A bolus of lidocaine (2 mg kg?1) administered 10 minutes after xylazine-butorphanol in calves deepened the degree of sedation but did not decrease the requirement of ketamine for endotracheal intubation. No adverse effects were recorded in the physiological variables measured.  相似文献   

10.

Objective

To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α2-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs.

Study design

Crossover experimental study.

Animals

Six healthy, adult Beagle dogs weighing 12.6 ± 0.9 kg (mean ± standard deviation).

Methods

Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO2 and temperature were maintained at 40 ± 5 mmHg (5.3 ± 0.7 kPa) and 38 ± 0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg?1 then 1.5 μg kg?1 hour?1 and 4.5 μg kg?1 then 4.5 μg kg?1 hour?1) or MK-467 (90 μg kg?1 then 90 μg kg?1 hour?1 and 180 μg kg?1 then 180 μg kg?1 hour?1); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at p < 0.05.

Results

Sevoflurane MAC decreased significantly from 1.86 ± 0.3% to 1.04 ± 0.1% and 0.57 ± 0.1% with incremental doses of dexmedetomidine. Sevoflurane MAC significantly increased with high dose MK-467, from 1.93 ± 0.3% to 2.29 ± 0.5%.

Conclusions and clinical relevance

Dexmedetomidine caused a dose-dependent decrease in sevoflurane MAC, whereas MK-467 caused an increase in MAC at the higher infusion dose. Further studies evaluating the combined effects of dexmedetomidine and MK-467 on MAC and cardiovascular function may elucidate potential benefits of the addition of a peripheral α2-adrenergic antagonist to inhalation anesthesia in dogs.  相似文献   

11.

Objective

The aim was to compare efficacy and side effects of induction with medetomidine–ketamine or medetomidine–S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia.

Study design

Prospective, blinded, randomized experimental study in two centres.

Animals

Eighty-three healthy New Zealand White rabbits undergoing tibial or ulnar osteotomy.

Methods

Medetomidine (0.2 mg kg?1) with 10 mg kg?1 ketamine (MK) or 5 mg kg?1 S(+)-ketamine (MS) was administered IN to each rabbit in a randomized fashion. In Centre 1 (n = 42) rabbits were held in sternal recumbency, and in Centre 2 (n = 41) in dorsal recumbency, during drug instillation. Adverse reactions were recorded. If a rabbit swallowed during endotracheal intubation, half of the initial IN dose was repeated and intubation was re-attempted after 5 minutes. Anaesthesia was maintained with isoflurane. Heart rate, blood pressure, endtidal carbon dioxide concentration and blood gases were recorded. Data were analysed using Student's t-test, Mann–Whitney test and Fisher's exact test.

Results

In all, 39 animals were assigned to the MK group and 44 to the MS group. Two rabbits in the MS group held in dorsal recumbency died after instillation of the drug. Eight (MK) and 11 rabbits (MS) were insufficiently anaesthetized and received a second IN dose. One rabbit in MK and three in MS required an isoflurane mask induction after the second IN dose. There were no significant differences between treatments for induction, intraoperative data, blood gas values and recovery data.

Conclusion and clinical relevance

This study indicated that medetomidine–ketamine and medetomidine-S(+)-ketamine were effective shortly after IN delivery, but in dorsal recumbency IN administration of S(+)-ketamine led to two fatalities. Nasal haemorrhage was noted in both cases; however, the factors leading to death have not been fully elucidated.  相似文献   

12.

Objective

To characterize the pharmacokinetics of dexmedetomidine when administered as a short intravenous (IV) infusion to isoflurane-anesthetized rabbits.

Study design

Experimental study.

Animals

A total of six healthy adult female New Zealand White rabbits.

Methods

Rabbits were anesthetized with isoflurane in oxygen. Following determination of isoflurane minimum alveolar concentration (MAC), the anesthetic dose was reduced to 0.7 × MAC, and dexmedetomidine hydrochloride (20 μg kg?1) was infused IV over 5 minutes. Arterial blood samples were obtained immediately before and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240 and 360 minutes following termination of the infusion. Samples were transferred into tubes containing ethylenediaminetetraacetic acid and centrifuged immediately. The plasma was harvested and stored at –80 °C until analyzed. Concentrations of dexmedetomidine in plasma were determined by liquid chromatography mass spectrometry. Compartment models were fitted to the time and concentration data using nonlinear regression.

Results

A three-compartment model best fit the data set. Median volume of distribution at steady state and terminal half-life were 3169 mL kg?1 (range, 2182–3859 mL kg?1) and 80 minutes (range, 72–88 minutes), respectively.

Conclusions and clinical relevance

The pharmacokinetics of dexmedetomidine in isoflurane-anesthetized, healthy, New Zealand White rabbits were characterized in this study. Data from this study can be used to determine dosing regimens for dexmedetomidine in isoflurane-anesthetized rabbits.  相似文献   

13.

Objective

To characterize a propofol–medetomidine-ketamine total intravenous anaesthetic in impala (Aepyceros melampus).

Study design

Prospective clinical study.

Animals

Ten adult female impala.

Materials and methods

Impala were immobilized at 1253 m above sea level with 2.0 mg thiafentanil and 2.2 mg medetomidine via projectile darts. Propofol was given to effect (0.5 mg kg?1 boluses) to allow endotracheal intubation, following which oxygen was supplemented at 2 L minute?1. Anaesthesia was maintained with a constant-rate infusion of medetomidine and ketamine at 5 μg kg?1 hour?1 and 1.5 mg kg?1 hour?1, respectively, and propofol to effect (initially 0.2 mg kg?1 minute?1) for 120 minutes. The propofol infusion was titrated according to reaction to nociceptive stimuli every 15 minutes. Cardiopulmonary parameters were monitored continuously and arterial blood gas samples were analysed intermittently. After 120 minutes' maintenance, the thiafentanil and medetomidine were antagonized using naltrexone (10:1 thiafentanil) and atipamezole (5:1 medetomidine), respectively.

Results

All impala were successfully immobilized. The median dose [interquartile range (IQR)] of propofol required for intubation was 2.7 (1.9–3.3) mg kg?1. The propofol–medetomidine–ketamine combination abolished voluntary movement and ensured anaesthesia for the 120 minute period. Propofol titration showed a generally downward trend. Median (IQR) heart rate [57 (53–61) beats minute?1], respiratory rate [10 (9–12) breaths minute?1] and mean arterial blood pressure [101 (98–106) mmHg] were well maintained. Arterial blood gas analysis indicated hypoxaemia, hyper- capnia and acidaemia. Butorphanol (0.12 mg kg?1) was an essential rescue drug to counteract thiafentanil-induced respiratory depression. All impala regurgitated frequently during the maintenance period. Recovery was calm and rapid in all animals. Median (IQR) time to standing from antagonist administration was 4.4 (3.2–5.6) minutes.

Conclusions and clinical relevance

A propofol–medetomidine–ketamine combination could provide adequate anaesthesia for invasive procedures in impala. The propofol infusion should begin at 0.2 mg kg?1 minute?1 and be titrated to clinical effect. Oxygen supplementation and airway protection with a cuffed endotracheal tube are essential.  相似文献   

14.

Objective

To evaluate whether intratesticular and incisional ropivacaine infiltration produces sufficient intra- and postoperative analgesia for castrating dogs under sedation.

Study design

Randomized, blinded, controlled clinical study.

Animals

Twenty-three healthy dogs weighing 5.8–35.6 kg admitted for castration.

Methods

Dogs were sedated with medetomidine (0.01 mg kg?1), butorphanol (0.2 mg kg?1) and midazolam (0.2 mg kg?1) intramuscularly, and were randomly assigned to group R, 0.2–0.4 mL kg?1 of ropivacaine 0.5%, or group S, an equivalent volume of saline injected intratesticularly and along the incision line. If persistent motion was observed during surgery, sedation was considered to be insufficient and general anaesthesia was induced. Carprofen 2.2 mg kg?1 was administered postoperatively. Pain was evaluated in all dogs before sedation and postoperatively following atipamezole administration at 1, 2, 4, 8 and 24 hours using an interactive visual analogue scale (IVAS; 0–100), the Glasgow composite pain scale-short form (CMPS-SF; 0–24), and a mechanical algometer. Methadone 0.3 mg kg?1 was administered intravenously to dogs if IVAS >30 or CMPS-SF >4.

Results

There was no significant difference between groups for the number of dogs administered general anaesthesia. The time from the beginning of surgery to induction of general anaesthesia was significantly shorter [median (range)] in group S [6 (3–25) minutes] than in group R [56 (36–76) minutes]. At 8 hours IVAS was significantly higher in group S (14 ± 10) than in group R (6 ± 4).

Conclusions and clinical relevance

Intratesticular and incisional ropivacaine infiltration delayed the time to anaesthesia induction, and provided analgesia after castration performed under deep sedation in dogs. Intratesticular local anaesthesia can be an important part of the anaesthetic plan for castration.  相似文献   

15.

Objective

To study the effect of heterothermia on anaesthetic drug requirements in semi-free ranging Arabian oryx and to assess the temperature quotient (Q10) of oxygen consumption.

Study design

Prospective observational study and controlled metabolic experiment.

Animals

Sixty-eight anaesthetic events in 59 Arabian oryx from Mahazat As-Sayd protected area, Saudi Arabia

Methods

Anaesthesia was induced by remote injection of 25 mg ketamine, 10 mg midazolam and 0.5 mg medetomidine with a variable amount of etorphine based on a target dosage of 20 μg kg–1 and subjective assessment of body mass. Animals not recumbent within 15 minutes or insufficiently anaesthetized were physically restrained and administered supplementary etorphine intravenously depending on the anaesthetic depth. Body temperature (Tb) was measured rectally immediately upon handling of each animal. From six anaesthetized oryx, expiratory gasses for oxygen analysis and metabolic rate calculation were collected at two Tbs; before and after submersion in ice water for approximately 30 minutes.

Results

Forty-two animals (62%) became recumbent with the initial dose, with a mean induction time (± standard deviation) of 9 ± 2 minutes. The remaining animals could be handled but needed 0.3 ± 0.1 mg etorphine intravenously to reach the desired level of anaesthesia. There was a significant positive correlation between Tb and effective etorphine dosage (R2 = 0.48, p < 0.0001). Average Tb of the six animals in which metabolic rate was measured decreased from 40.0 ± 0.5°C immediately after induction to 35.5 ± 0.5°C after cooling. This reduction was associated with a reduction in oxygen uptake from 3.11 ± 0.33 to 2.22 ± 0.29 mL O2 minute–1 kg–1, reflected in Q10 of 2.17 ± 0.14.

Conclusions and clinical relevance

Tb significantly affects anaesthetic requirements in Arabian oryx and should be considered when selecting dosages for anaesthetic induction for species showing diurnal heterothermy.  相似文献   

16.

Objective

To determine the anti-inflammatory efficacy of choline in vivo and in vitro and to investigate the anti-inflammatory mechanisms of choline.

Study design

Randomized, controlled studies.

Animals

In vivo trials used 16 Romney sheep. In vitro experiments utilized RAW 264.7 mouse macrophage cells.

Methods

Hypoxaemia induced in 16 sheep by intravenous (IV) injection of 50 μg kg–1 xylazine, an α-2 agonist, was measured in sheep at 0, 1 and 4 minutes using arterial blood gas analysis with and without 50 mg kg–1 IV choline chloride premedication. Cell culture studies used enzyme-linked immunosorbent assay to measure the release of tumour necrosis factor (TNF-α) from lipopolysaccharide (LPS) stimulated macrophages with and without choline chloride premedication. TNF-α release was compared to thalidomide suppressed and untreated cells.

Results

Choline premedication in sheep mitigated a reduction in arterial partial pressure of oxygen (PaO2) but did not prevent development of clinically significant hypoxaemia. Decrease in mean PaO2 of choline treated sheep was 6.36 kPa (47.7 mmHg) compared to 9.81 kPa (73.6 mmHg) in control sheep. In vitro studies demonstrate that choline administered concurrent with LPS activation did not significantly suppress TNF-α expression but that treatment of cells with choline 10 minutes prior to LPS activation did significantly suppress TNF-α expression. Choline pretreated cells expressed 23.99 ± 4.52 ng mg–1 TNF-α while LPS only control cells expressed 33.83 ± 3.20 ng mg–1.

Conclusions

Choline is able to prevent macrophage activation in vitro when administered prior to LPS activation and may reduce hypoxaemia in sheep developing pulmonary oedema after xylazine administration. This effect requires premedication with choline.

Clinical relevance

Pharmacological manipulation of autonomic inflammatory responses holds promise for the treatment of inflammation. However, the complex cellular mechanisms involved in this reflex means that an adequate therapy should approach multiple pathways and mechanisms of the inflammatory response.  相似文献   

17.

Objective

To investigate the sedative effects in dogs of tiletamine–zolazepam–acepromazine (TZA) or ketamine–flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs.

Study design

Experimental study followed by a field trial.

Animals

Six research dogs and 27 free-roaming dogs.

Methods

In a pilot study, six research dogs were administered liquid TZA (20 mg kg?1 tiletamine–zolazepam and 2 mg kg?1 acepromazine) or liquid KF (50 mg kg?1 ketamine and 2 mg kg?1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs.

Results

In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35–80) minutes (67%); treatment 2, 30 (15–65) minutes (83%); and treatment 3, 75 (45–110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg?1) and acepromazine (2 mg kg?1). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg?1) and xylazine (1.1–2.2 mg kg?1) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food.

Conclusions and clinical relevance

Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate.  相似文献   

18.

Objective

To evaluate the onset, magnitude and duration of thermal antinociception after oral administration of two doses of tapentadol in cats.

Study design

Prospective, randomized, blinded, experimental study.

Animals

Six healthy adult cats weighing 4.4 ± 0.4 kg.

Methods

Skin temperature (ST) and thermal threshold (TT) were evaluated using a wireless TT device up to 12 hours after treatment. Treatments included placebo (PBO, 50 mg dextrose anhydrase orally), buprenorphine (BUP, 0.02 mg kg?1) administered intramuscularly, low-dose tapentadol (LowTAP, 25 mg orally; mean 5.7 mg kg?1) and high-dose tapentadol (HighTAP, 50 mg orally; mean 11.4 mg kg?1) in a blinded crossover design with 7 day intervals. Statistical analysis was performed using anova with appropriate post hoc test (p ≤ 0.05).

Results

Salivation was observed immediately following 11 out of 12 treatments with tapentadol. The ST was significantly increased at various time points in the opioid treatments. Hyperthermia (≥ 39.5 °C) was not observed. Baseline TT was 45.4 ± 1.4 °C for all treatments. Maximum TT values were 48.8 ± 4.8 °C at 1 hour in LowTAP, 48.5 ± 3.0 °C at 2 hours in HighTAP and 50.2 ± 5.3 °C at 1 hour in BUP. TT significantly increased after LowTAP at 1 hour, after HighTAP at 1–2 hours, and after BUP at 1–2 hours compared with baseline values. TTs were significantly increased in BUP at 1–2 hours compared with PBO.

Conclusion and clinical relevance

Oral administration of tapentadol increased ST and TT in cats. The durations of thermal antinociception were similar between HighTAP and BUP, both of which were twice as long as that in LowTAP. Studies of different formulations may be necessary before tapentadol can be accepted into feline practice.  相似文献   

19.
20.

Objective

To assess the temporal effects of a single fentanyl intravenous (IV) bolus on the minimum anesthetic concentration (MAC) of isoflurane in chickens and to evaluate the effects of this combination on heart rate (HR) and rhythm, systemic arterial pressures (sAP) and ventilation.

Study design

Prospective experimental trial.

Animals

Seventeen adult chickens weighing 1.8 ± 0.2 kg.

Methods

Individual isoflurane MAC for 17 chickens was previously determined using the bracketing method. Chickens were anesthetized with isoflurane to evaluate the effects of a single IV fentanyl bolus (10 or 30 μg kg?1) on isoflurane MAC over time using the up-and-down method. Ventilation was controlled. The isoflurane MAC reduction was estimated by logistic regression at 5 and 15 minutes after fentanyl administration. In the second phase, seven chickens were anesthetized with isoflurane, and fentanyl was administered (30 μg kg?1) IV over 1 minute during spontaneous ventilation and HR and rhythm, sAP and ventilation variables were measured.

Results

At 5 minutes after IV administration of fentanyl (10 or 30 μg kg?1), isoflurane MAC was significantly reduced by 17.6% (6.1–29.1%) [logistic regression estimate (95% Wald confidence interval)] and 42.6% (13.3–71.9%), respectively. Isoflurane MAC reduction at 15 minutes after IV administration of fentanyl (10 or 30 μg kg?1) was 6.2% (?0.6 to 12.9%) and 13.2% (?0.9 to 27.3%), respectively; however, this reduction was not significant. No clinically significant cardiopulmonary changes or arrhythmias were detected after the administration of fentanyl (30 μg kg?1).

Conclusions and clinical relevance

Administration of a single fentanyl bolus induced a dose-dependent and short-lasting reduction in isoflurane MAC. The higher dose induced no significant cardiopulmonary depression in isoflurane-anesthetized chickens during spontaneous ventilation. In chickens anesthetized with isoflurane, the clinical usefulness of a single fentanyl bolus is limited by its short duration of effect.  相似文献   

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