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1.
OBJECTIVE: To evaluate effects of polymyxin B sulfate (PMB) on response of horses to endotoxin, using an ex vivo model. ANIMALS: 8 healthy horses. PROCEDURE: In a crossover design, 3 doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and physiologic saline solution (control) were evaluated. Prior to and for 24 hours after administration of PMB, blood samples were collected into heparinized tubes for use in 2 assays. For the endotoxin-induced tumor necrosis factor (TNF) assay, blood samples were incubated (37 C for 4 h) with 1 ng of Escherichia coli or Salmonella Typhimurium endotoxin/ml of blood. Plasma was harvested and assayed. For the residual endotoxin activity assay, plasma was collected into sterile endotoxin-free borosilicate tubes, diluted 1:10 with pyrogen-free water, and incubated for 10 minutes at 70 C. Escherichia coli endotoxin (0.1 or 1 ng/ml of plasma) was added to the thawed samples prior to performing the limulus ameobocyte lysate assay. Serum creatinine concentrations were monitored for 1 week. RESULTS: Compared with baseline values, PMB caused a significant dose- and time-dependent decrease in endotoxin-induced TNF activity. Compared with baseline values, residual endotoxin activity was significantly reduced after administration of 10,000 U of PMB/kg. Compared with baseline values, 1,000 and 5,000 U of PMB/kg should inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours, respectively. Serum creatinine concentrations remained within the reference range. CONCLUSION AND CLINICAL RELEVANCE: Results of the study suggest that PMB is a safe, effective inhibitor of endotoxin-induced inflammation in healthy horses.  相似文献   

2.
Reasons for performing the study: Endotoxaemia causes substantial morbidity and mortality in horses with colic and sepsis. Ethyl pyruvate is a novel anti‐inflammatory medication that improved survival in preclinical models of severe sepsis endotoxaemia and intestinal ischaemia and reperfusion in rodents, swine, sheep and dogs and may be a useful medication in horses. Hypothesis: Ethyl pyruvate has no adverse effects in normal horses and is biologically active based on suppression of proinflammatory gene expression in endotoxin stimulated whole blood, in vitro. Methods: Physical and neurological examinations, behaviour scores, electrocardiograms and clinicopathological tests were performed on 5 normal healthy horses receiving 4 different doses of ethyl pyruvate. Doses included 0, 50, 100 and 150 mg/kg bwt administered in a randomised crossover design with a 2 week washout period between doses. Biological efficacy was assessed by stimulating whole blood with endotoxin from the horses that received ethyl pyruvate prior to and 1 and 6 h after drug infusion. Gene expression for TNFα, IL‐1β and IL‐6 was assessed. Results: There were no effects of drug or dose (0, 50, 100 or 150 mg/kg bwt) on any of the physical or neurological examination, behaviour factors, electrocardiogram or clinical pathological results collected from any of the horses. All parameters measured remained within the normal reference range. There was a significant reduction in TNFα, IL‐1β and IL‐6 gene expression in endotoxin stimulated whole blood from horses 6 h after receiving 150 mg/kg bwt ethyl pyruvate. There were no detectable effects on gene expression of any of the other doses of ethyl pyruvate tested. Conclusion: We were unable to detect any detrimental effects of ethyl pyruvate administration in normal horses. Ethyl pyruvate significantly decreased proinflammatory gene expression in endotoxin stimulated blood 6 h after drug administration. Clinical relevance: Ethyl pyruvate may be a safe, effective medication in endotoxaemic horses.  相似文献   

3.
Reasons for performing the study: Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are limited for these horses. Ethyl pyruvate (EP), an anti‐inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses. Objectives: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (LPS) in horses. Methods: Horses received 30 ng/kg bwt LPS in saline to induce signs of endotoxaemia. Next, horses received lactated Ringer's solution (LRS), (n = 6), 150 mg/kg bwt EP in LRS, (n = 6), or 1.1 mg/kg bwt flunixin meglumine (FM), (n = 6). Controls received saline followed by LRS (n = 6). Physical examinations, behaviour pain scores and blood for clinical pathological testing and gene expression were obtained at predetermined intervals for 24 h. Results: Lipopolysaccharide infusion produced clinical and clinicopathological signs of endotoxaemia and increased expression of tumour necrosis factor alpha (TNFα), interleukin 6 (IL‐6) and IL‐8 (P<0.001) compared with controls. Leucopenia and neutropenia occurred in all horses that received LPS. Horses treated with EP and FM had significantly (P<0.0001) reduced pain scores compared with horses receiving LPS followed by LRS. Flunixin meglumine was significantly more effective at ameliorating fever compared with EP. Both EP and FM significantly diminished TNFα expression. Ethyl pyruvate significantly decreased, but FM significantly increased, IL‐6 expression. Neither EP nor FM altered IL‐8 expression. Conclusions and potential relevance: Ethyl pyruvate administered following LPS diminished the clinical effects of endotoxaemia and decreased proinflammatory gene expression in horses. Ethyl pyruvate suppressed expression of proinflammatory cytokines better than FM. However, FM was a superior anti‐pyretic compared with EP. Ethyl pyruvate may have therapeutic applications in endotoxaemic horses.  相似文献   

4.
REASONS FOR PERFORMING STUDY: Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. HYPOTHESIS: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. METHODS: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined. RESULTS: Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities. CONCLUSIONS: Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor). POTENTIAL RELEVANCE: Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.  相似文献   

5.
REASONS FOR PERFORMING STUDY: It has been reported that i.v. flecainide has a high efficacy for the treatment of experimentally-induced acute atrial fibrillation (AF) in horses and that its use is associated with minimal toxic side effects. OBJECTIVES: The objectives were to study the efficacy of i.v. flecainide as a treatment for atrial fibrillation in horses with naturally-occurring AF. METHODS: Ten horses with naturally-occurring AF were treated with 2 mg/kg bwt flecainide i.v. at a rate of 0.2 mg/kg bwt/min. In 3 horses, the infusion was continued at 0.05-0.10 mg/kg bwt/min until a total dose of 3.0 mg/kg bwt had been administered. Heart rate, QRS duration and average interval between fibrillation waves were measured before, during and following flecainide infusion. If conversion to normal sinus rhythm was not achieved, horses were treated with quinidine sulphate per os at a dose of 22 mg/kg bwt given every 2 h. RESULTS: None of the horses with chronic AF (n = 9) converted to sinus rhythm with flecainide i.v. The only horse treated successfully had acute AF of 12 days' duration. The QRS duration and fibrillation cycle length increased significantly (P = 0.006 and 0.002, respectively) during and following flecainide infusion. Heart rate did not increase significantly over time however, 3 horses developed heart rates in excess of 100 beats/min. Two horses developed a potentially dangerous ventricular dysrhythmia during the first 15 mins of treatment. Quinidine sulphate given per os restored sinus rhythm in 8 out of 9 horses, with minimal adverse effects. CONCLUSIONS: Although flecainide might be efficacious in cases of acute AF, it was not possible to restore sinus rhythm in horses with naturally-occurring chronic AF at the dosages used in this study. In 2 horses, 2.0 mg/kg bwt flecainide was associated with potentially dangerous dysrhythmias. POTENTIAL CLINICAL RELEVANCE: Intravenous administration of 2 mg/kg bwt flecainide is unlikely to convert chronic AF in horses and could induce dangerous dysrhythmias.  相似文献   

6.
REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. OBJECTIVES: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.  相似文献   

7.
REASONS FOR PERFORMING STUDY: Lidocaine constant rate infusions (CRIs) are common as an intraoperative adjunct to general anaesthesia, but their influence on quality of recovery has not been thoroughly determined. OBJECTIVES: To determine the effects of an intraoperative i.v. CRI of lidocaine on the quality of recovery from isoflurane or sevoflurane anaesthesia in horses undergoing various surgical procedures, using a modified recovery score system. HYPOTHESIS: The administration of intraoperative lidocaine CRI decreases the quality of recovery in horses. METHODS: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min) or saline was administered for the duration of surgery or until 30 mins before the end of surgery under isoflurane (n = 27) and sevoflurane (n = 27). RESULTS: Horses receiving lidocaine until the end of surgery had a significantly higher degree of ataxia and a tendency towards significance for a lower quality of recovery. There was no correlation between lidocaine plasma concentrations at recovery and the quality of recovery. CONCLUSIONS: Intraoperative CRI of lidocaine affects the degree of ataxia and may decrease the quality of recovery. POTENTIAL RELEVANCE: Discontinuing lidocaine CRI 30 mins before the end of surgery is recommended to reduce ataxia during the recovery period.  相似文献   

8.
OBJECTIVE: To quantify plasma and urine nitric oxide (NO) concentrations before and after low-dose endotoxin infusion in horses. ANIMALS: 11 healthy adult female horses. Procedure-Eight horses were given endotoxin (35 ng/kg of body weight,i.v.) over 30 minutes. Three sentinel horses received an equivalent volume of saline (0.9% NaCl) solution over the same time. Clinical signs of disease and hemodynamic variables were recorded, and urine and plasma samples were obtained to measure NO concentrations prior to endotoxin infusion (t = 0) and every hour until postinfusion hour (PIH) 6, then every 2 hours until PIH 24. Blood for hematologic and metabolic analyses and for serum cytokine bioassays were collected at 0 hour, every hour until PIH 6, every 2 hours through PIH 12, and finally, every 6 hours until PIH 24. RESULTS: Differences in plasma NO concentrations across time were not apparent, but urine NO concentrations significantly decreased at 4 and 20 to 24 hours in endotoxin-treated horses. Also in endotoxin-treated horses, alterations in clinical signs of disease, and hemodynamic, metabolic, and hematologic variables were significant and characteristic of endotoxemia. Serum interleukin-6 (IL-6) activity and tumor necrosis factor (TNF) concentrations were increased above baseline values from 1 to 8 hours and 1 to 2 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma and urine NO concentrations did not increase in horses after administration of a low dose of endotoxin, despite induction of an inflammatory response, which was confirmed by increased TNF and IL-6 values characteristic alterations in clinical signs of disease, and hematologic, hemodynamic and metabolic variables.  相似文献   

9.
REASONS FOR PERFORMING STUDY: Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. HYPOTHESIS: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. METHODS: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). RESULTS: In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. CONCLUSIONS: Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated.  相似文献   

10.
REASONS FOR PERFORMING STUDY: High-dose dobutamine stress echocardiography has been shown to be cardiotoxic and arrhythmogenic in horses. However, the test may have benefit in practice as a pharmacological challenge of exercise without the treadmill being required. OBJECTIVES: To investigate the effect of low-dose dobutamine on cardiac performance in ponies previously treated with atropine, in order to develop a pharmacological protocol that allows examination of the equine heart under stimulation. METHODS: In 13 healthy Shetland ponies, heart rate (HR), stroke index (SI) and cardiac index (CI) were calculated from pulsed-wave Doppler ultrasound measurements performed at rest and during incremental steps of dobutamine infusion. Group 1 (n = 7) received dobutamine infusion at 2 microg/kg bwt/min for 5 mins followed by incremental rates of 5 microg/kg bwt/min every 5 mins, from 5 to 40 microg/kg bwt/min. Group 2 (n = 6) received dobutamine infusion in incremental rates of 1 microg/kg bwt/min, every 5 mins, from 2 microg/kg bwt/min to 5 microg/kg bwt/min, after premedication with 2 injections of 25 microg/kg bwt of atropine 5 mins apart. RESULTS: The increase in CI during the pharmacological challenge was higher in Group 2 and reached about 2.5 times the resting value. This increase in CI was mediated by a significant increase in HR in both groups, while SI significantly decreased in Group 1 and did not change significantly in Group 2. Ponies of Group 1, but not those of Group 2, showed excessive restlessness and cardiac arrhythmias during the pharmacological challenge and a high intragroup variability in cardiac response. CONCLUSIONS: The results of this study suggest that a low dose of dobutamine in ponies previously given atropine could be a helpful pharmacological protocol to perform stress echocardiography in equids. POTENTIAL RELEVANCE: Further studies should evaluate left ventricular wall motion in horses undergoing low-dose dobutamine protocol after pretreatment with atropine.  相似文献   

11.
REASONS FOR PERFORMING STUDY: Endotoxaemia is one of the most severe and ubiquitous disease processes in horses. Although dimethyl sulphoxide (DMSO) is used clinically in horses, there is no study indicating its efficacy in endotoxaemic horses. HYPOTHESIS: DMSO ameliorates the clinical response to i.v. lipopolysaccharide (LPS) administration. METHODS: Eighteen horses were assigned randomly to one of 4 groups: Normosol-LPS (0.2 mug/kg bwt, i.v.); DMSO (1 g/kg bwt, i.v.)-saline; high-dose DMSO (1 g/kg bwt, i.v.)LPS; low-dose DMSO (20 mg/kg bwt, i.v.)-LPS. Horses participating in the DMSO-saline group were later assigned randomly to one of the LPS groups. Data for physical parameters, white blood cell counts, plasma TNF-alpha, and blood lactate and glucose concentrations were examined for the effect of treatment using a repeated-measures mixed-model ANOVA. A value of P<0.05 was considered significant. RESULTS: Endotoxaemia occurred in all horses receiving LPS, as indicated by the clinical score, physical parameters, haemoconcentration and leucopenia. High-dose DMSO ameliorated the effect of LPS on fever. DMSO, at either dose, but did not have a significant effect on LPS-induced changes in all other evaluated parameters. CONCLUSIONS: In this study, DMSO had minimal effects on clinical signs of induced endotoxaemia in horses. The effects were manifested by amelioration of LPS-induced fever.  相似文献   

12.
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   

13.
REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.  相似文献   

14.
REASONS FOR PERFORMING STUDY: Commonly used analgesics (nonsteroidal anti-inflammatory agents, opioids and alpha2-agonists) have unwanted side effects. An effective alternative with minimal adverse effects would benefit clinical equine pain management. OBJECTIVES: To compare the effect of lidocaine or saline on duodenal and rectal distension threshold pressure and somatic thermal threshold in conscious mature horses. HYPOTHESIS: Systemically administered lidocaine would increase somatic and visceral nociceptive thresholds. METHODS: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min for 2 h) or saline was administered to 6 horses each carrying a permanently implanted gastric cannula, in a randomised, blinded cross-over design. Thermal threshold was measured using a probe containing a heater element placed over the withers which supplied heat until the horse responded. A barostatically controlled intraduodenal balloon was distended until a discomfort response was obtained. A rectal balloon was inflated until extruded or signs of discomfort noted. RESULTS: Thermal threshold was increased significantly 30 and 90 mins after the start of lidocaine infusion. There was no change in duodenal distension pressure and a small but clinically insignificant change in colorectal distension pressure in the lidocaine group. CONCLUSIONS: At the dose used, systemically administered lidocaine produced thermal antinociception but minimal changes in visceral nociception. POTENTIAL RELEVANCE: At these doses, lidocaine may play a role in somatic analgesia in horses.  相似文献   

15.
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   

16.
Reasons for performing study: Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objectives: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1–5 mg/kg bwt) of 10% propofol. Trial 3: 6 horses were sedated with xylazine (0.5 mg/kg bwt, i.v.) and assigned randomly to receive 10% propofol (3, 4 or 5 mg/kg bwt, i.v.); anaesthesia was maintained for 60 min using an infusion of 1% propofol (0.2‐0.4 mg/kg bwt/min). Cardiorespiratory data, the quality of anaesthesia, and times for induction, maintenance and recovery from anaesthesia and the number of attempts to stand were recorded. Results: Trial 1 was terminated after 2 horses had received each dose of 10% propofol. The quality of induction, anaesthesia and recovery from anaesthesia was judged to be unsatisfactory. Trial 2: 3 horses administered 1 mg/kg bwt and one administered 2 mg/kg bwt were not considered to be anaesthetised. Horses administered 3–5 mg/kg bwt i.v. propofol were anaesthetised for periods ranging from approximately 10–25 min. The PaO2 was significantly decreased in horses administered 3–5 mg/kg bwt i.v. propofol. Trial 3: The quality of induction and recovery from anaesthesia were judged to be acceptable in all horses. Heart rate and rhythm, and arterial blood pressure were unchanged or decreased slightly during propofol infusion period. Conclusions: Anaesthesia can be induced with a 10% propofol solution and maintained with a 1% propofol solution in horses administered xylazine as preanaesthetic medication. Hypoventilation and hypoxaemia may occur following administration to mature horses. Potential relevance: Adequate preanaesthetic sedation and oxygen supplementation are required in horses anaesthetised with propofol.  相似文献   

17.
REASONS FOR PERFORMING STUDY: It has been suggested that rapid administration of isotonic saline solution relieves airway obstruction in heaves-affected horses, but the efficacy and tolerability of this treatment is poorly documented. OBJECTIVES: To determine the respiratory and metabolic effects of a rapid administration of isotonic saline solution in control horses and those with heaves. METHODS: Thirty litres isotonic saline solution were administered i.v. to 5 control (Group C) and 9 heaves-affected horses (Group H). Pulmonary function testing and arterial blood gas analysis were performed prior to saline infusion, at 90 and 180 mins after starting the infusion, and 1, 3, 6 and 10 days later. PCV, plasma total solids, plasma electrolytes (Na+, Cl- and K+) and venous blood gas analysis were performed prior, during and after saline infusion. RESULTS: Rapid saline administration was shown to have no beneficial effects on lung function during infusion in Group H. On the contrary, they had significantly increased pulmonary resistance (RL) at 180 mins following the initiation of saline administration compared to baseline. In Group C, saline administration resulted in a significant increase in RL at 180 mins and a significant decrease in PaO2 at 90 mins. These results suggest a transient decrement in lung function caused by rapid saline administration. Group H had a metabolic alkalosis with hypochloraemia at baseline compared to control horses. This resolved following i.v. saline administration and returned to baseline within 6 h after treatment had been discontinued. CONCLUSION: The administration of saline to Group H did not improve airway function significantly, but resulted in mild and transient side effects. POTENTIAL RELEVANCE: Rapid administration of isotonic saline alone is not an effective therapy for heaves in horses.  相似文献   

18.
Twenty-five horses admitted for minor orthopaedic or soft tissue surgery were anaesthetised with detomidine, ketamine and halothane. Heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, blood gases and occlusion pressures were measured before and for 30 mins after intravenous (iv) injection of saline, butorphanol 0.05 mg/kg bodyweight (bwt) or morphine 0.02 or 0.05 mg/kg bwt. Drug or saline treatment induced no significant changes from pre-treatment values within a group for arterial blood pressure, heart rate, respiratory rate, arterial carbon dioxide tension, arterial oxygen tension and occlusion pressure. In conclusion, both morphine and butorphanol at the stated doses cause no adverse effects on the cardiovascular and respiratory systems of anaesthetised horses.  相似文献   

19.
Serum tumor necrosis factor (TNF) activity was quantitated in 8 horses given an IV infusion of endotoxin (0.03 micrograms of lipopolysaccharide/kg of body weight, from Escherichia coli 055:B5) in 0.9% NaCl solution over 1 hour. Serum TNF activity was likewise measured in 6 horses given only 0.9% sterile NaCl solution at the same rate. The duration of serum TNF activity was determined, and serum TNF activity was correlated with clinical and laboratory changes during the induced endotoxemia. Horses had no serum TNF activity prior to endotoxin administration, but geometric mean serum TNF activity was significantly higher from 1 to 4 hours after the start of the infusion. In response to endotoxin, horses seemed depressed, had signs of mild to moderate abdominal pain, developed tachycardia and fever, and had leukopenia followed by leukocytosis. Association between serum TNF activity and temperature, heart rate, attitude abnormality score, and WBC count of horses given endotoxin was significant. Serum TNF activity had a significant positive linear correlation with attitude abnormality and heart rate and a negative linear correlation with the WBC count during endotoxemia. Geometric mean serum TNF activity peaked approximately 1.5 hours prior to mean peak fever, and these data were significantly correlated. Results of this study suggest that TNF is an important mediator of endotoxemia in horses.  相似文献   

20.
REASON FOR PERFORMING STUDY: Good results have been obtained with a human amiodarone (AD) i.v. protocol in horses with chronic atrial fibrillation (AF) and a pharmacokinetic study is required for a specific i.v. amiodarone treatment protocol for horses. OBJECTIVES: To study the efficacy of this pharmacokinetic based i.v. AD protocol in horses with chronic AF. METHODS: Six horses with chronic AF were treated with an adapted AD infusion protocol. The protocol consisted of 2 phases with a loading dose followed by a maintenance infusion. In the first phase, horses received an infusion of 6.52 mg AD/kg bwt/h for 1 h followed by 1.1 mg/kg bwt/h for 47 h. In the second phase, horses received a second loading dose of 3.74 mg AD/kg bwt/h for 1 h followed by 1.31 mg/kg bwt/h for 47 h. Clinical signs were monitored, a surface ECG and an intra-atrial electrogram were recorded. AD treatment was discontinued when conversion or any side effects were observed. RESULTS: Three of the 6 horses cardioverted successfully without side effects. The other 3 horses did not convert and showed adverse effects, including diarrhoea. In the latter, there were no important circulatory problems, but the diarrhoea continued for 10-14 days. The third horse had to be subjected to euthanasia because a concomitant Salmonella infection worsened the clinical signs. CONCLUSION: The applied treatment protocol based upon pharmacokinetic data achieved clinically relevant concentrations of AD and desethylamiodarone. POTENTIAL RELEVANCE: Intravenous AD has the potential to be an alternative pharmacological treatment for AF in horses, although AD may lead to adverse drug effects, particularly with cumulative dosing.  相似文献   

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