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1.
Carolina Rinse Solution (CRS) was applied topically and intraluminally to ischaemic (Group 1; n = 5) and distended equine jejunum (Group 2; n = 5). Mesenteric blood flow, ORC (osmotic reflection coefficient), wet weight to dry weight ratios (WW/DW), serosal thickness, and neutrophil accumulation in the serosa were measured. After 60 min ischaemia followed by reperfusion (Group 1), mesenteric blood flow remained greater than baseline values. The mean ORC was similar to that previously reported in normal bowel or ischaemic intestine treated with CRS by arterial perfusion. The ORC after distention and decompression (Group 2) increased and was similar to that previously reported in a comparable untreated experimental model. The WW/DW after both ischaemia and distention increased compared to specimens collected from noninstrumented jejunum proximal to the experimental segments in the same horses. There was no difference in neutrophil numbers in the serosa of either ischaemic or distended intestine compared to the noninstrumented proximal jejunum. CRS-treated ischaemic intestine maintained microvascular permeability similar to that reported for normal intestine whereas treated distended intestine did not. Combined topical and intraluminal application of CRS to ischaemic intestine may reduce complications due to acute inflammation during reperfusion.  相似文献   

2.
Evaluation of substance P as a neurotransmitter in equine jejunum   总被引:2,自引:0,他引:2  
OBJECTIVE: To determine whether substance P (SP) functions as a neurotransmitter in equine jejunum. SAMPLE POPULATION: Samples of jejunum obtained from horses that did not have lesions in the gastrointestinal tract. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscle, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 2 intensities (30 and 70 V) and various frequencies on muscle strips that were maintained at low tension or were under contraction. A neurokinin-1 receptor blocker (CP-96,345) was added to baths prior to EFS to interrupt SP neurotransmission. Additionally, direct effects of SP on muscle strips were evaluated, and SP-like immunoreactivity was localized in intestinal tissues, using indirect immunofluorescence testing. RESULTS: Substance P contracted circularly and longitudinally oriented muscle strips. Prior treatment with CP-96,345 altered muscle responses to SP and EFS, suggesting that SP was released from depolarized myenteric neurons. Depending on orientation of muscle strips and stimulation variables used, CP-96,345 increased or decreased the contractile response to EFS. Substance P-like immunoreactivity was detected in the myenteric plexus and circular muscle layers. CONCLUSIONS AND CLINICAL RELEVANCE: Substance P appears to function as a neurotransmitter in equine jejunum. It apparently modulates smooth muscle contractility, depending on preexisting conditions. Effects of SP may be altered in some forms of intestinal dysfunction. Altering SP neurotransmission in the jejunum may provide a therapeutic option for motility disorders of horses that are unresponsive to adrenergic and cholinergic drugs.  相似文献   

3.
REASONS FOR PERFORMING STUDY: The most common cause of death as a direct result of colic is acute circulatory failure secondary to intestinal ischaemia. Early and accurate recognition of ischaemic bowel is essential to decrease complications and increase survival. Blood to peritoneal lactate values have been evaluated as a prognostic indicator, but lactate values characterised by type of lesion have not been reported. HYPOTHESIS: Plasma and peritoneal lactate values are higher in horses with intestinal ischaemia secondary to a strangulating obstruction (ISSO). METHODS: Venous blood and peritoneal fluid were collected sequentially from 20 clinically healthy horses and 189 horses admitted for colic during a one-year period. Blood gas, pH, electrolyte (K+, Na+, Ca++, Cl-), glucose and lactate values were determined for blood and peritoneal fluid samples; other values recorded for peritoneal fluid included gross appearance, total protein and nucleated cell count. Information regarding diagnosis, treatment and outcome was retrieved from the medical records. RESULTS: Peritoneal and plasma levels of lactate were lower in control compared to clinical cases. Horses with ISSO had a higher peritoneal lactate value (8.45 mmol/l) than those with nonstrangulating obstruction (2.09 mmo/l). Factors with the strongest correlations with the presence of ISSO were changes in the gross appearance of the peritoneal fluid and values of peritoneal fluid chloride, pH and log10 lactate. CONCLUSIONS: Analysis of peritoneal fluid gross appearance, pH, lactate and chloride can be used for diagnosis of ISSO. POTENTIAL RELEVANCE: Peritoneal fluid lactate is a better predictor of ISSO than blood lactate and may aid in early detection of catastrophic peritoneal lesions such as intestinal strangulation and rupture.  相似文献   

4.
The efficacy of partial arytenoidectomy was assessed in 6 Standardbred horses, with surgically induced laryngeal hemiplegia, at rest (Period A) and during exercise at speeds corresponding to maximum heart rate (Period C) and 75% of maximum heart rate (Period B). Peak expiratory and inspiratory airflow rate (PEF and PIF), and expiratory and inspiratory transupper airway pressure (PUE and PUI) were measured and expiratory and inspiratory impedance (ZE and ZI) were calculated. Simultaneously, tidal breathing flow-volume loops (TBFVL) were acquired using a respiratory function computer. Indices derived from TBFVL included airflow rates at 50 and 25% of tidal volume (EF50, IF50, EF25. and IF25) and the ratios of expiratory to inspiratory flows. Measurements were made before left recurrent laryngeal neurectomy (baseline), 2 weeks after left recurrent laryngeal neurectomy (LRLN) and 16 weeks after left partial arytenoidectomy coupled with bilateral ventriculectomy (ARYT). After LRLN, during exercise Periods B and C, Z1 and the ratio of EF50/IF50 significantly increased and PIF, IF50 and IF25 significantly decreased from baseline values. At 16 weeks after ARYT, Z1 returned to baseline values during Periods B and C. Although PIF, IF50, IF25, PEF/PIF, and EF50/IF50 returned to baseline values during Period B, these indices remained significantly different from baseline measurements during Period C. After ARYT, TBFVL shapes from horses during Period C approached that seen at the baseline evaluation. Partial arytenoidectomy improved upper airway function in exercising horses with surgically induced left laryngeal hemiplegia, although qualitative and quantitative evaluation of TBFVLs suggested that some flow limitation remains at near maximal airflow rates. These results indicate that, although the procedure does not completely restore the upper airway to normal, partial arytenoidectomy is a viable treatment option for failed laryngoplasty and arytenoid chondropathy in the horse.  相似文献   

5.
OBJECTIVE: To evaluate effects of Carolina rinse solution, dimethyl sulfoxide (DMSO), and 21-aminosteroid, U-74389G, on microvascular permeability and morphology of the equine jejunum after low-flow ischemia and reperfusion. ANIMALS: 20 healthy adult horses. PROCEDURE: Under anesthesia, full-thickness biopsy specimens of a distal portion of the jejunum were obtained for baseline measurements. In addition to a control segment, 2 jejunal segments were identified as sham-operated or experimental segments. Experimental segments underwent 60 minutes of low-flow ischemia and 3.5 hours of reperfusion. Treatments were as follows: U-74389G (3 mg/kg, IV; 6 horses), DMSO (20 mg/kg, IV; 6) diluted in 1 L of saline (0.9% NaCl) solution, local perfusion (via jejunal artery) of Carolina rinse solution (0.5 mL/kg; 4), and local perfusion of lactated Ringer's solution (0.5 mL/kg; 4). RESULTS: Jejunal microvascular permeability was significantly lower after treatment with Carolina rinse solution or DMSO, compared with U-74389G or lactated Ringer's solution treatments. After DMSO treatment, serosal- and submucosal-layer edema was significantly increased in experimental segments, compared with control or sham-operated segments; however, edema increases were significantly less than for lactated Ringer's solution or U-74389G treatments. Significant decreases in intestinal wet weight-to-dry weight ratio were found following Carolina rinse solution or DMSO treatments, compared with lactated Ringer's solution or U-74389G treatments. Edema formation and leukocyte infiltration in jejunal segments of horses treated with lactated Ringer's solution or U-74389G were increased, compared with Carolina rinse solution or DMSO treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Carolina rinse solution and DMSO may be protective against ischemia-reperfusion injury in the equine jejunum.  相似文献   

6.
OBJECTIVE: To determine effect of leukocyte depletion on hematologic, morphologic, and metabolic variables of equine jejunum after induction of arterial low-flow ischemia and reperfusion by use of an extracorporeal circuit. ANIMALS: 14 healthy adult horses. PROCEDURE: A segment of jejunum was surgically removed and maintained in an isolated circuit for 3 hours (control group), arterial flow was reduced to 20% of baseline for 40 minutes followed by 1 hour of reperfusion (low-flow group), or leukocyte depletion was filter-induced, and low-flow ischemia and reperfusion were conducted as in the low-flow control group (filter-treated group). Various metabolic, hemodynamic, and histomorphologic variables were evaluated, including effects of electrical field stimulation and L-N-nitro-arginine-methyl-ester (L-NAME) on contractile activity. RESULTS: The extracorporeal circuit appeared to maintain the jejunum within physiologic limits for an extended period. Low-flow ischemia with reperfusion induced significant differences in various measurements, compared with control specimens. Significant differences were not detected between the low-flow and filter-treated groups. Myeloperoxidase activity was greater in the low-flow group than the control group, whereas a difference was not detected between control and filter-treated groups. CONCLUSIONS AND CLINICAL RELEVANCE: The extracorporeal circuit maintained intestine for 3 hours in a physiologic state and may be used for simulation of tissue injury. Leukocyte depletion generally did not attenuate the effects of low-flow ischemia and reperfusion on equine small intestine.  相似文献   

7.
A study was undertaken to evaluate the significance and mechanism of reperfusion injury in the equine large colon following 1 h of haemorrhagic strangulation obstruction (HSO) or ischaemic strangulation obstruction (ISO) and to assess the effect of treatment with dimethyl sulphoxide (DMSO). ISO or HSO were created 40 cm from the pelvic flexure and maintained for 60 mins under general anaesthesia. Normal saline or 20 per cent DMSO (1 g/kg bodyweight) was administered intravenously 10 mins prior to the end of the ischaemic period. Four groups of four horses in a 2 x 2 factorial design were used. Treatments of HSO or ISO and DMSO given (yes or no) were utilised. Intestinal wall biopsies and right colic arterial and venous blood samples were taken at 0, 60, 90 and 120 mins following initiation of the obstructions. Histological evaluation of the intestine using haematoxylin and eosin stained sections and immunohistochemical staining for albumin were performed. Mucosal and serum reduced glutathione (GSH) and oxidised glutathione (GSSG) levels and the amount of lymphatic dilatation with albumin and submucosal pooling of albumin were used as indirect measures of oxygen free radical production. Histopathological changes were minimal after 1 h of either type of ischaemia. Progressive changes during the post ischaemic period were minimal for ISO and moderate for HSO. Serum GSH and GSSG levels were not detectable. There was no demonstrable benefit of DMSO treatment as assessed by histology, immunohistochemistry or preservation of GSH levels in the mucosa. In conclusion, a reperfusion injury following 60 mins of ischaemia could not be detected in this study.  相似文献   

8.
To investigate a model for equine endometritis, 12 mares with normal reproductive tracts were divided into 2 groups. All mares received progesterone in oil, 250 mg im, daily. At 5 days after initiation of progesterone administration, the uteri were inoculated with 10(6) colony forming units of Pseudomonas aeruginosa. The day of inoculation was designated Day 0. On Day 6, endometrial swab samples yielded P. aeruginosa in 5 mares; samples from the other 7 mares yielded heavy growth of Escherichia coli, Streptococcus zooepidemicus, Klebsiella pneumoniae, Enterobacter spp., Citrobacter diversus, Staphylococcus epidermidis and Streptococcus morbillorum. On Days 6, 7 and 8, Group A mares received intrauterine infusions of 6 g ticarcillin disodium and 0.2 g clavulanate potassium in 100 ml sterile saline. Group B mares received infusions of saline only. The incidence of swab specimens yielding no bacterial growth was significantly higher in Group A than Group B mares on Days 8 and 13 (4/6 vs 0/6). Swab samples from 5 of the 6 mares in Group A yielded growth of fungi on Days 13 and 19. Mares in Group B were then similarly treated with ticarcillin/clavulanate infusions, on Days 19, 20 and 21. The incidence of swab specimens yielding no bacterial growth was 2/6 and 1/6 on Days 21 and 26, respectively; fungi were not recovered from these mares at any time. The incidence of no-growth swabs after antibiotic treatment tended to be higher in Group A and incidence of fungal recovery after antibiotic treatment was significantly higher in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

9.
OBJECTIVES: To evaluate the efficacy of an isolated perfusion circuit and the effect of ischemia-reperfusion on mucosal permeability of the jejunum. STUDY DESIGN: In vitro study of intestinal mucosal permeability. ANIMALS: Twelve healthy adult horses. METHODS: A control segment of jejunum was placed in an isolated perfusion circuit for 240 minutes and mucosal permeability was measured. After detecting no deleterious effects of the isolated system on the control intestine, low flow ischemia was created in experimental segments for 20, 40, 60 and 90 minutes followed by 60 minutes of reperfusion and mucosal permeability was evaluated. At the completion of the studies, histologic evaluation was used to determine mucosal grades, surface area, and volume. RESULTS: Control tissue was maintained in the isolated circuit for 240 minutes without effect on mucosal grade, surface area, or volume relative to intact tissue. After ischemia-reperfusion, mucosal grade increased, and volume and surface area decreased progressively with longer periods of ischemia. Mucosal clearance of albumin remained constant during 240 minutes of perfusion in control tissue and was elevated after ischemia-reperfusion. CONCLUSIONS: No deleterious changes were noted in jejunum perfused with this isolated circuit, whereas alterations in mucosal permeability were present after ischemia-reperfusion. CLINICAL RELEVANCE: The isolated perfusion circuit successfully maintained an isolated segment of jejunum within physiologic limits, and can be used to evaluate the effects of injury and the efficacy of pharmaceuticals to attenuate these changes.  相似文献   

10.
REASON FOR PERFORMING STUDY: The cytosolic protein complex, calprotectin, is abundant in neutrophils and could be used to improve the ability to localise and assess neutrophil infiltration in the equine intestine during ischaemia and reperfusion (I/R), but further study is required. OBJECTIVES: To assess the number of calprotectin-containing cells by immunohistochemistry in correlation with direct counting and scoring of neutrophils in the equine colon during I/R. METHODS: One and 2 h ischaemia of the left dorsal colon were induced, followed by 30 min reperfusion under general anaesthesia or by 18 h reperfusion after anaesthetic recovery. Biopsies were processed for light microscopy and stained with H/E for detection of neutrophils. To identify calprotectin-containing cells, immunohistochemistry was performed on formalin-fixed tissues with the murine MAC 387 antibody and a biotin-free peroxidase staining procedure. The number of neutrophils within submucosal venules and the colonic mucosa were calculated and compared with the number of calprotectin-positive cells. RESULTS: The number of calprotectin-positive cells within submucosal venules and within the colonic mucosa correlated significantly with the accumulation of neutrophils within the corresponding tissue segments. Within the submucosal venules, both calprotectin-positive cells and H/E-stained neutrophils increased with duration of ischaemia and peaked after 30 min of reperfusion. After 18 h reperfusion the number of these cells declined within the vessels. After 2 h ischaemia, neutrophils started to migrate into the mucosa towards the epithelium, with a significant increase over time during reperfusion, and peak infiltration after 18 h reperfusion. CONCLUSIONS: Neutrophil infiltration into the colon after I/R is a time-dependent process, involving migration through the submucosa towards the epithelium.  相似文献   

11.
Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro/in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioavailability in the horse. Permeability was ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the bioavailability (R(2) = 0.633447), the Log P (R(2) = 0.648517), as well as the molecular weight (R(2) = 0.851208) of the drugs. Metronidazole induced a decrease in the tissue transepithelial resistance, suggestive of the possibility of tissue toxicity, which may have falsely increased its permeability. The low permeability of cephalexin across the tissue may indicate a lack of active transporters that are found in other species. From this study, we can conclude that the Ussing chamber is a promising method for determining mucosal permeability in the horse.  相似文献   

12.
OBJECTIVE: To determine whether a customized solution could attenuate the effects of low-flow ischemia and reperfusion injury of the equine jejunum. SAMPLE POPULATION: A segment of jejunum obtained from 21 healthy adult horses. PROCEDURE: A segment of jejunum was maintained in an isolated extracorporeal circuit, and arterial flow was reduced to 20% of baseline for 40 minutes (ischemia) followed by 60 minutes of reperfusion. In 1 group, a customized solution was infused at a rate of 1 ml/min during low-flow ischemia and 3 ml/min during reperfusion. In a second group, the solution was infused at the same rate during low-flow ischemia, but it was infused at a rate of 7 ml/min during reperfusion. Control groups received lactated Ringer's solution administered at the same rates as for the customized solution. Various metabolic, hemodynamic, histologic, and permeability variables were recorded. RESULTS: A lower flow rate during reperfusion (3 ml/min) had a beneficial effect, compared with lactated Ringer's solution or the higher flow rate (7 ml/min). Use of the solution at this rate resulted in less histomorphologic injury and reduced mucosal permeability to albumin. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a customized solution at a lower flow rate during repurfusion appeared to have a protective effect on equine jejunum when administered IV during low-flow ischemia and reperfusion.  相似文献   

13.
14.
OBJECTIVE: To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion. ANIMALS: 24 horses. PROCEDURE: Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, i.v., q 12 h), flunixin meglumine (1.1 mg/kg, i.v., q 12 h), or etodolac (23 mg/kg, i.v., q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithelial flux of tritium-labeled mannitol measured mucosal permeability. Denuded villous surface area and mean epithelial neutrophil count per mm2 were calculated. Western blot analysis for cyclooxygenase (COX)-1 and -2 was performed. Pharmacokinetics of flunixin and etodolac and eicosanoid concentrations were determined. RESULTS: Ischemic-injured tissue from horses treated with flunixin and etodolac had significantly lower TER and increased permeability to mannitol, compared with that from horses treated with saline solution. Epithelial denudation after ischemia and 18 hours after recovery was not significantly different among treatments. Both COX-1 and -2 were expressed in ischemic-injured and nonischemic tissues. Ischemia caused significant upregulation of both COX isoforms. Eicosanoid concentrations were significantly lower in tissues from flunixin and etodolac-treated horses, compared with that from horses treated with saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Flunixin and etodolac treatment retarded recovery of intestinal barrier function in jejunal mucosa after 18 hours of reperfusion, whereas tissues from horses treated with saline solution recovered baseline values of TER and permeability to mannitol.  相似文献   

15.
We evaluated the efficacy of buparvaquone in eliminating Babesia equi of European origin in carrier horses and in experimentally infected splenectomized ponies. When administered at the rate of 2.5 mg/kg of body weight, IM, 4 times at 96-hour intervals, buparvaquone was effective in eliminating B equi carrier infection in 1 horse. Such results could not be repeated at the same dosage or at 3.5 or 5 mg/kg, IM. Buparvaquone given at the rate of 4 to 6 mg/kg IV and/or IM was therapeutically effective in 4 of 5 acute B equi infections in splenectomized ponies. The treated ponies became carriers.  相似文献   

16.
17.
OBJECTIVE: To evaluate the efficacy of a customized solution to attenuate intestinal injury following 20% low-flow ischemia and reperfusion in the jejunum of horses. ANIMALS: 10 healthy adult horses. PROCEDURE: Two 30.5-cm-long segments of jejunum were exteriorized through a ventral midline incision and the mesenteric artery and vein supplying that portion of the intestine were instrumented with flow probes. Blood flow was decreased to 20% of baseline for 90 minutes followed by 90 minutes of reperfusion. In 5 horses, 60 mL of the customized solution was placed in the lumen of each segment (treatment-group horses), and 60 mL of lactated Ringer's solution was placed in the lumen of 5 additional horses (control-group horses). Biopsy specimens were obtained from 1 segment in both groups for histologic evaluation. Aliquots of luminal fluid were obtained from the other segment in both groups for determination of albumin concentrations as an index of mucosal permeability. RESULTS: Compared with control-group horses, treatment-group horses had a significant decrease in luminal albumin concentration following reperfusion. Although differences in mucosal grades were not significantly different between control- and treatment-group horses, treatment-group horses had significantly greater jejunal villous length and area, compared with that of control-group horses. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal administration of the customized solution in the jejunum, compared with lactated Ringer's solution, results in an improvement in histologic findings and mucosal translocation of albumin in horses with mild intestinal injury.  相似文献   

18.
OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.  相似文献   

19.
OBJECTIVE: To evaluate equine IgG as a treatment for kittens with failure of passive transfer of immunity (FPT). ANIMALS: 13 specific pathogen-free queens and their 77 kittens. PROCEDURE: Kittens were randomized at birth into 9 treatment groups. One group contained colostrum-fed (nursing) kittens; the other groups contained colostrum-deprived kittens that were administered supplemental feline or equine IgG PO or SC during the first 12 hours after birth. Blood samples were collected at serial time points from birth to 56 days of age for determination of serum IgG concentrations. The capacity of equine IgG to opsonize bacteria for phagocytosis by feline neutrophils was determined via flow cytometry. RESULTS: Kittens that received feline or equine IgG SC had significantly higher serum IgG concentrations than those of kittens that received the supplements PO. In kittens that were administered supplemental IgG SC, serum IgG concentrations were considered adequate for protection against infection. The half-life of IgG in kittens treated with equine IgG was shorter than that in kittens treated with feline IgG. Feline IgG significantly enhanced the phagocytosis of bacteria by feline neutrophils, but equine IgG did not. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of equine IgG that are considered protective against infection are easily attained in kittens, but the failure of these antibodies to promote bacterial phagocytosis in vitro suggests that equine IgG may be an inappropriate treatment for FPT in kittens.  相似文献   

20.
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   

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