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1.
Polymyxin‐B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin‐B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 μg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin‐B (10–3000 μg/ml). A murine L929 fibroblast bioassay was used to measure TNF‐α activity. Polymyxin‐B significantly inhibited the effects of all three bacterial toxins. Analysis of variance showed the IC50 value for polymyxin‐B for TNF‐α inhibition caused by LTA (11.19 ± 2.89 μg/ml polymyxin‐B) was significantly lower (p = .009) than the values for LPS (46.48 ± 9.93 μg/ml) and PGN (54.44 ± 8.97 μg/ml). There was no significant difference in IC50 values between LPS and PGN (p > .05). Maximum inhibition of TNF‐α was 77.4%, 73.0% and 82.7% for LPS, PGN and LTA, respectively and was not significantly different between toxins. At the two highest concentrations of polymyxin‐B, TNF‐α began to increase. These data suggest that polymyxin‐B may inhibit the effects of bacterial toxins other than LPS and might be a more potent inhibitor of LTA than LPS or PGN.  相似文献   

2.
Background: Ketamine as continuous rate infusion (CRI) provides analgesia in hospitalized horses. Objective: Determine effects of prolonged CRI of ketamine on gastrointestinal transit time, fecal weight, vital parameters, gastrointestinal borborygmi, and behavior scores in healthy adult horses. Animals: Seven adult Thoroughbred or Thoroughbred cross horses, with permanently implanted gastric cannulae. Methods: Nonblinded trial. Random assignment to 1 of 2 crossover designed treatments. Ketamine (0.55 mg/kg IV over 15 minutes followed by 1.2 mg/kg/h) or lactated Ringer's solution (50 mL IV over 15 minutes followed by 0.15 mL/kg/h) treatments. Two hundred 3 × 5 mm plastic beads administered by nasogastric tube before drug administration. Every 2 hours vital parameters, behavior scores recorded, feces collected and weighed, and beads retrieved. Every 6 hours gastrointestinal borborygmi scores recorded. Study terminated upon retrieval of 180 beads (minimum 34 hours) or maximum 96 hours. Nontransit time data analyzed between hours 0 and 34. Results: No significant (P < .05) differences detected between treatments in vital signs or gastrointestinal borborygmi. Significant (P = .002) increase in behavior score during ketamine infusion (0.381) from hours 24–34 compared with placebo (0). Ketamine caused significant delay in passage of 25, 50, and 75% of beads (ketamine = 30.6 ± 5.3, 41.4 ± 8.4, 65.3 ± 13.5 hours versus placebo = 26.8 ± 7.9, 34.3 ± 11.1, 45.8 ± 19.4 hours), and significant (P < .05) decrease in fecal weight from hours 22 (12.6 ± 3.2 versus 14.5 ± 3.8 kg) through 34 (18.5 ± 3.9 versus 12.8 ± 6.4 kg) of infusion. Conclusions and Clinical Importance: Ketamine CRI delayed gastrointestinal transit time in healthy horses without effect on vital parameters.  相似文献   

3.
OBJECTIVE: To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURES: In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS: Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.  相似文献   

4.
Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, nonesterified fatty acids, and muscle enzyme levels were measured, as were plasma concentrations of KET and its metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Levels of sedation and muscle tension were scored. Respiration and heart rate significantly increased during the early infusion phase. Glucose and cortisol significantly varied both during and after infusion. During CRI all horses scored 0 on sedation. All but one horse scored 0 on muscle tension, with one mare scoring 1. All other parameters remained within or close to physiological limits without significant changes from pre-CRI values. The mean plasma concentration of KET during the 1.5 mg/kg/h KET CRI was 235 ng/mL. The decline of its plasma concentration-time curve of both KET and norketamine (NKET) following the CRI was described by a two-compartmental model. The metabolic cascade of KET was NKET, hydroxynorketamine (HNK), and 5,6-dehydronorketamine (DHNK). The KET median elimination half-lives (t1/2alpha and t1/2beta) were 2.3 and 67.4 min, respectively. The area under the KET plasma concentration-time curve (AUC), elimination was 76.0 microg.min/mL. Volumes of C1 and C2 were 0.24 and 0.79 L/kg, respectively. It was concluded that a KET CRI of 1.5 mg/kg/h can safely be administered to healthy conscious horses for at least 6 h, although a slight modification of the initial infusion rate regimen may be indicated. Furthermore, in the horse KET undergoes very rapid biotransformation to NKET and HNK and DHNK were the major terminal metabolites.  相似文献   

5.
Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods After xylazine pre‐medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg?1; THIO 6 mg kg?1 + PRO 0.5 mg kg?1; THIO 4 mg kg?1 + PRO 1 mg kg?1; THIO 2 mg kg?1 + PRO 1.5 mg kg?1; KET 2 mg kg?1; KET 1.5 mg kg?1 + PRO 0.5 mg kg?1; KET 1 mg kg?1 + PRO 1 mg kg?1; KET 0.5 mg kg?1 + PRO 1.5 mg kg?1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, first movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration differed significantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO‐8 (mean ± SD, 0.5 ± 0.3 minutes) and longest in horses receiving KET‐2 (1.4 ± 0.2 minutes). The best scores for induction quality were associated with KET‐1.5 + PRO‐0.5, and the worst scores for induction quality were associated with KET‐2, although the difference was not significant. Time to first movement varied significantly among drug protocols (p = 0.0133), being shortest in horses receiving KET‐2 (12.7 ± 3.6 minutes) and longest in horses receiving THIO‐8 (29.9 ± 1.5 minutes). Horses receiving THIO‐8 made the greatest number of attempts to attain sternal posture (6.5 ± 4.7) and to stand (1.6 ± 0.8). Horses in the THIO‐8 treatment also received the poorest recovery scores (3.3 ± 1.0 and 3.0 ± 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modifies behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine.  相似文献   

6.
OBJECTIVE: To evaluate the effects of ketamine, diazepam, and the combination of ketamine and diazepam on intraocular pressures (IOPs) in clinically normal dogs in which premedication was not administered. ANIMALS: 50 dogs. PROCEDURES: Dogs were randomly allocated to 1 of 5 groups. Dogs received ketamine alone (5 mg/kg [KET5] or 10 mg/kg [KET10], IV), ketamine (10 mg/kg) with diazepam (0.5 mg/kg, IV; KETVAL), diazepam alone (0.5 mg/kg, IV; VAL), or saline (0.9% NaCl) solution (0.1 mL/kg, IV; SAL). Intraocular pressures were measured immediately before and after injection and at 5, 10, 15, and 20 minutes after injection. RESULTS: IOP was increased over baseline values immediately after injection and at 5 and 10 minutes in the KET5 group and immediately after injection in the KETVAL group. Compared with the SAL group, the mean change in IOP was greater immediately after injection and at 5 and 10 minutes in the KET5 group. The mean IOP increased to 5.7, 3.2, 3.1, 0.8, and 0.8 mm Hg over mean baseline values in the KET5, KET10, KETVAL, SAL, and VAL groups, respectively. All dogs in the KET5 and most dogs in the KETVAL and KET10 groups had an overall increase in IOP over baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with baseline values and values obtained from dogs in the SAL group, ketamine administered at a dose of 5 mg/kg, IV, caused a significant and clinically important increase in IOP in dogs in which premedication was not administered. Ketamine should not be used in dogs with corneal trauma or glaucoma or in those undergoing intraocular surgery.  相似文献   

7.
Horses are exquisitely sensitive to bacterial endotoxin and endotoxaemia is common in colic cases. In this study, gene expression of inflammatory cytokines was characterised in the blood of healthy horses following i.v. administration of lipopolysaccharide (LPS). Six horses received an LPS infusion and 6 controls received an equivalent volume of saline. Gene expression of genes encoding interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐8, and tumour necrosis factor‐α (TNF‐α) was quantified by real‐time PCR. Gene expression of all inflammatory cytokines was upregulated following administration of LPS. Interleukin‐1α, IL‐1β, IL‐8 and TNF‐α gene expression peaked at 60 min, while IL‐6 expression peaked at 90 min post LPS infusion. Interleukin‐1β and IL‐6 messenger RNA expression levels were above the baseline values 3 h post LPS infusion, whereas IL‐1α, IL‐8 and TNF‐α expression levels returned to baseline values by 3 h after LPS infusion. It was concluded that LPS infusion upregulated gene expression of inflammatory cytokines in the blood of healthy horses.  相似文献   

8.
Background: The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Hypothesis: Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Animals: Twelve horses. Methods: Two equal groups (n = 6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by a 6‐hour continuous rate infusion of GI or GII (0.05 mg/kg BW/min). Treatment efficacy was judged from change in arterial blood pressure, peripheral blood and peritoneal fluid (PF) variables (total and differential cell counts, enzyme activities, and cytokine concentrations), and clinical scores (CS) for behavioral evidence of abdominal pain or discomfort during the study. Results: Compared with the control group, horses treated with lidocaine had significantly lower CS and serum and PF tumor necrosis factor‐α (TNF‐α) activity. At several time points in both groups, total and differential cell counts, glucose, total protein and fibrinogen concentrations, and alkaline phosphatase, creatine kinase, and TNF‐α activities were significantly different from baseline values both in peripheral blood and in PF. Conclusions and Clinical Importance: Lidocaine significantly decreased severity of CS and inhibited TNF‐α activity in PF.  相似文献   

9.
Donalisio, C., Barbero, R., Cuniberti, B., Vercelli, C., Casalone, M., Re, G. Effects of flunixin meglumine and ketoprofen on mediator production in ex vivo and in vitro models of inflammation in healthy dairy cows. J. vet. Pharmacol. Therap.  36 , 130–139. In this study, ex vivo assays were carried out in dairy cows to evaluate the anti‐inflammatory effects of two nonsteroidal anti‐inflammatory drugs: ketoprofen (KETO) and flunixin meglumine (FM). Twelve healthy Holstein dairy cattle were randomly allocated to two groups (n=6): group 1 received FM and group 2 received KETO at recommended therapeutic dosages. The anti‐inflammatory effects of both drugs were determined by measuring the production of coagulation‐induced thromboxane B2 (TXB2), lipopolysaccharides (LPS) (10 μg/mL)‐induced prostaglandin E2 (PGE2), and calcium ionophore (60 μm )‐induced leukotrien B4 (LTB4). Cytokine production was assessed by measuring tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ) and interleukin‐8 (CXCL8) concentrations after incubation in the presence of 10 μg/mL LPS. The IC50 of FM and KETO was determined in vitro by determining the concentration of TXB2 and PGE2 in the presence of scalar drug concentrations (10?9–10?3 m ). Both FM and KETO inhibited the two COX isoforms in vitro, but showed a preference for COX‐1. FM and KETO showed similar anti‐inflammatory effects in the cow.  相似文献   

10.
Ketamine has been implicated as causing increases in intraocular pressure. The purpose of this study is to document the effects of ketamine, diazepam, and their combination on intraocular pressure (IOP) in normal, unpremedicated dogs. Random-source dogs were assigned to one of five groups of 10 dogs each: ketamine 5 mg kg–1 (KET5), ketamine 10 mg kg–1 (KET10), diazepam 0.5 mg kg–1 (VAL), ketamine 10 mg kg–1 with diazepam 0.5 mg kg–1 (KETVAL), saline 0.1 mL kg–1 (SAL), all given intravenously. A baseline IOP was measured before injection, immediately after injection, and at 5, 10, 15, and 20 minutes following injection. IOP was increased over baseline immediately after injection in the KET5, KET10, and KETVAL groups; at 5, 10, and 15 minutes in the KET5 group; and at 20 minutes in the KETVAL group. The mean IOP change compared to SAL increased immediately after injection and at 5 minutes in the KET5, KET10, and KETVAL groups; at 10 and 15 minutes in the KET5 group, and at 20 minutes in the KETVAL group. The mean IOP increased up to 5.7, 3.2, and 3.1 mm Hg over mean baseline in the KET5, KET10, and KETVAL groups, respectively. All dogs in the KET5 group and the majority in the KETVAL and KET10 groups had an increase in their IOP over baseline. Ketamine caused a clinically and statistically significant elevation in IOP over baseline and compared to SAL. The concurrent addition of diazepam did not blunt this increase. Ketamine should be avoided in dogs with corneal trauma, glaucoma, or in those undergoing intraocular surgery.  相似文献   

11.
ObjectiveTo evaluate the perioperative opioid-sparing effect of a medetomidine (MED) infusion compared to a saline (SAL) infusion in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery.Study designRandomized, partially blinded, clinical study.AnimalsA total of 44 client-owned adult dogs.MethodsAll dogs were administered a 1 μg kg–1 MED loading dose, followed by a 1.7 μg kg–1 hour–1 constant rate infusion (CRI) intravenously or equivalent volumes of SAL. Infusions were started 10–15 minutes before surgical incision and continued throughout the surgical procedure. All dogs were administered a standardized anaesthetic and analgesic protocol (including a ketamine CRI). Multiparametric monitoring, including invasive arterial blood pressure, was performed. A trained investigator, unaware of the treatment, performed pain scores for 4 hours postoperatively. Rescue analgesia consisted of fentanyl administered intraoperatively and methadone postoperatively. Data were tested for normality and analysed with Fisher’s exact test, Mann–Whitney U-test, analysis of variance and Kaplan–Meier survival analysis. Data are shown as median (interquartile range) and p-value was set at < 0.05.ResultsThe total dose of fentanyl was significantly lower with MED 0 (0–0.8) μg kg–1 hour–1 compared to SAL 3 (1.8–5.3) μg kg–1 hour–1 (p = 0.004). In the MED group, one dog compared to 12 dogs in the SAL group required a fentanyl CRI (p = 0.001). There were no statistically significant differences between groups regarding the total dose of methadone administered.Conclusions and clinical relevanceThe addition of a low-dose medetomidine CRI to the anaesthetic protocol decreased the need for a fentanyl CRI in otherwise healthy dogs undergoing thoraco-lumbar hemilaminectomy surgery during administration of a ketamine CRI.  相似文献   

12.
OBJECTIVE: To determine whether infusion of xylazine (XYL) and ketamine (KET) for 30 minutes after isoflurane administration in horses would result in improved quality of recovery from anesthesia, without detrimental cardiopulmonary changes. STUDY DESIGN: Randomized, blinded experimental trial. ANIMALS: Seven healthy adult horses aged 6.4 +/- 1.9 years and weighing 506 +/- 30 kg. METHODS: Horses were anesthetized twice, at least 1 week apart. On both occasions, anesthesia was induced by the administration of XYL, diazepam, and KET, and maintained with isoflurane for approximately 90 minutes, the last 60 minutes of which were under steady-state conditions (1.2 times the minimum alveolar concentration isoflurane). On one occasion, horses were allowed to recover from isoflurane anesthesia, while on the other, XYL and KET were infused for 30 minutes after termination of isoflurane administration. Heart rate, respiratory rate, arterial blood pressure, pH, and blood-gases were measured and recorded at set intervals during steady-state isoflurane anesthesia and XYL-KET infusion. Recovery events were timed and subjectively scored by one nonblinded and two blinded observers. Data were analyzed using a restricted maximum likelihood-based mixed effect model repeated measures analysis. RESULTS: Infusion of XYL and KET resulted in longer recovery times, but there was no significant improvement in recovery quality score. CONCLUSIONS: Under the conditions of this study, infusion of XYL and KET does not positively influence recovery from isoflurane anesthesia in horses. CLINICAL RELEVANCE: This study does not support the routine use of XYL and KET infusions in horses during the transition from isoflurane anesthesia to recovery.  相似文献   

13.
ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg−1 racemic ketamine (group RS) or 0.3 mg kg−1 S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg−1minute−1 racemic ketamine (group RS) or 10 μg kg−1minute−1 S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL−1 of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL−1) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.  相似文献   

14.
Uterine inflammatory response is mediated by inflammatory mediators including eicosanoids and cytokines produced by immune and endometrial cells. Interactions between lipopolysaccharide (LPS) and cytokines, and leukotrienes (LTs) in endothelium, important for the host defence during the inflammation, are unknown. We studied the effect of LPS, tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐4 and IL‐10 on 5‐lipooxygenase (5‐LO), LTA4 hydrolase (LTAH) and LTC4 synthase (LTCS) mRNA and protein expression, LTB4 and LTC4 release from porcine endometrial endothelial cells, and cell viability. For 24 hr, cells were exposed to LPS (10 or 100 ng/ml of medium) and cytokines (each 1 or 10 ng/ml). 5‐LO mRNA/protein expression augmented after incubation with larger doses of LPS, TNF‐α, IL‐4 and IL‐10 and smaller dose of IL‐1β. Larger dose of TNF‐α, smaller doses of LPS and IL‐1β and both doses of IL‐10 increased LTAH mRNA/protein expression. LTAH protein content was up‐regulated by larger dose of LPS, but it was reduced in response to both doses of IL‐4. LTCS mRNA expression was elevated by larger doses of LPS, IL‐4 and IL‐10 or both doses of TNF‐α and IL‐1β. LTCS protein level increased after treatment with both doses of IL‐1β, IL‐4 and IL‐10, smaller dose of LPS and larger dose of TNF‐α. Both doses of LPS and larger doses of TNF‐α and IL‐10 increased LTB4 release. LPS, IL‐1β and IL‐10 at smaller doses, or TNF‐α and IL‐4 at larger doses stimulated LTC4 release. Smaller doses of TNF‐α and IL‐1β or both doses of IL‐4 enhanced the cell viability. This work provides new insight on the participation of LPS, TNF‐α, IL‐1β, IL‐4 and IL‐10 in LTB4 and LTC4 production/release from porcine endometrial endothelial cells, and the effect of above factors on these cells viability. The used cellular model gives the possibility to further establish the interactions between inflammatory mediators.  相似文献   

15.
Flunixin meglumine (FM) is a commonly used Nonsteroidal anti‐inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti‐inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)‐induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS‐induced Thromboxane B2 (TXB2) and Prostaglandin E2 (PGE2) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS‐induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti‐inflammatory and analgesic effects of KT is warranted.  相似文献   

16.
Arachidonic acid cyclooxygenase metabolites, thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 (6-keto-PGF1) were measured in horses where anaesthesia was maintained with halothane. Two horses suffering from postanaesthetic myositis were compared with four normal horses. TXB2 and PGE2 levels were higher in mixed venous blood drawn from the myopathic horses. An increase of TXB2 and PGE2 levels appeared when myopathic horses were rolled into dorsal recumbency after a prolonged period of lateral recumbency. One hour after the end of anaesthesia, TXB2 had continued to increase whereas PGE2 decreased. By measurements on blood samples drawn from the brachial vein, we have shown that the rising level of TXB2 in mixed venous blood is mainly due to the increase of TXB2 in blood draining the dependent leg. The origin of the rise in PGE2 is not demonstrated in this study. 6-keto-PGF1 did not change during anaesthesia. An explanation of this imbalance between TXB2 and 6-keto-PGF1 production is considered.  相似文献   

17.
When animals do not become pregnant, regression of the corpus luteum (CL) is essential for normal cyclicity because it allows the development of a new ovulatory follicle. Luteal regression is caused by a pulsatile release of prostaglandin (PG) F2α from the uterus in the late luteal phase in most mammals including cattle. Although it has been proposed in ruminants that pulsatile PGF2α secretion is generated by a positive feedback loop between luteal and/or hypophyseal oxytocin and uterine PGF2α, the bovine endometrium may possess other mechanisms for initiation of luteolytic PGF2α secretion. There is increasing evidence that several cytokines mainly produced by immune cells modulate CL and uterine function in many species. Tumor necrosis factor‐α (TNF‐α) stimulates PGF2α output from bovine endometrium not only at the follicular phase but also at the late luteal phase. Administration of TNF‐α at a high concentration prolongs luteal lifespan, whereas administration of a low concentration of TNF‐α accelerates luteal regression in cows. The data obtained from the authors’ previous in vitro and in vivo studies strongly suggest that TNF‐α is a crucial factor in regulating luteolysis in cows. The authors’ recent study has shown that interleukin‐1α mediates PG secretion from bovine endometrium as a local regulator. Furthermore, interferon‐τ (IFN‐τ) suppresses the action of TNF‐α on PGF2α synthesis by the bovine endometrium in vitro, suggesting that IFN‐τ plays a luteoprotective role by inhibiting TNF‐α‐induced PGF2α production in early pregnancy. The purpose of the present review is to summarize current understanding of the endocrine mechanisms that regulate uterine function by cytokines during the estrous cycle and early pregnancy in cows.  相似文献   

18.
Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg−1 hr−1 for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration–time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (Ke), half-life (t1/2e), volume of distribution (Vd), and clearance (Cl). Median and range were 0.42 (0.15–0.97)/hr, 1.68 (0.87–4.52) hr, 5.85 (2.10–19.34) L/kg, and 28.7 (19.6–39.5) ml min−1 kg−1, respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (Cmax) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.  相似文献   

19.
ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg?1, ketamine 2.2 mg kg?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO2 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO2 > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg?1 hour?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.  相似文献   

20.
REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Results: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Conclusions and clinical relevance: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.  相似文献   

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