Short-term intestinal ischemia-reperfusion alters intestinal motility that can be preserved by xanthine oxidase inhibition

While the effects of transient intestinal ischemia on mucosa have been well investigated, less is known about its effect on motor function. An experimental study was designed to investigate the effects of ischemia–reperfusion (I/R) on intestinal motility and intestinal muscular microcirculation. Wistar albino rats were divided into four groups: (1) baseline, (2) sham operation, (3) I/R, and (4) I/R with allopurinol pretreatment. Ischemia was induced by clamping the superior mesenteric artery (SMA) for 10 min. Gastroanal transit time (GATT) was measured with serial x-rays after instillation of barium sulfate to the stomach. Intestinal muscular microcirculation was evaluated by determining the number of carbon-perfused intestinal muscular microvessels (CPIMM). I/R prolonged GATT and decreased CPIMM significantly (P < 0.01). Pretreatment with allopurinol prevented prolongation of GATT and returned the number of CPIMM to the level of sham treatment (P < 0.01). In conclusion, reperfusion after 10 min of SMA ischemia alters intestinal motility. The no-reflow phenomenon plays an important role in this alteration of motility. Administration of allopurinol before reperfusion preserves intestinal motility by preventing the occurrence of no-reflow phenomenon.     

Effects of psychological stress on small intestinal motility and bacteria and mucosa in mice

AIM: To investigate the effects of psychological stress on small intestinal motility and bacteria and mucosa in mice, and to explore the relationship between small intestinal dysfunction and small intestinal motility and bacteria and mucosa under psychological stress. METHODS: Sixty mice were randomly divided into psychological stress group and control group. Each group were subdivided into small intestinal motility group (n= 10), bacteria group (n = 10), and D-xylose administered to stomach group (n= 10). An animal model with psychological stress was established housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as Iog10(colony forming units/g). D-xylose levels in plasma were measured for estimating trie damage of small intestinal mucosa. RESULTS: Small intestinal transit was inhibited (39.80±9.50% vs 58.79±11.47%,P<0.01) in mice after psychological stress, compared with the controls. Psychological stress resulted in quantitative alterations in the aerobes (E.coli). There was an increase in the number of E coli in the proximal small intestinal flora (1.78±0.30 log10(CFU/g) vs 1.37±0.21 log10(CFU/g), P<0.01), and there was decrease in relative proportion of Lactobacilli and E.coli of stressed mice (0.53±0.63 vs 1.14±1.07,P<0.05), while there was no significant difference in the anaerobes (Lactobacilli) between the two groups (2.31±0.70 log10 (CFU/g) vs 2.44±0.37 log10(CFU/g), P>0.05). D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (2.90±0.89 mmol/L vs 0.97±0.33 mmol/L, P<0.01). CONCLUSION: Small intestinal dysfunction under psychological stress may be related to the small intestinal motility disorder and dysbacteriosis and the damage of mucosa probably caused by psychological stress.     

Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test,suggesting bacterial overgrowth

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case–control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 ± 0.8 in IBS subjects and 2.2 ± 1.0 in controls (P < 0.000001). The duration of phase III was 305 ± 123 sec in IBS subjects and 428 ± 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.     

Vasoactive intestinal polypeptide appears to be one of the mediators in misoprostol-enhanced small intestinal transit in rats

BACKGROUND AND AIMS: Prostaglandin analogs have the pharmacologic effect of speeding up small intestinal transit (SIT). It remains unknown whether some gut peptides also mediate this enhancement. We studied the effect of misoprostol on rat SIT and looked at the role of vasoactive intestinal polypeptide (VIP) release during its action. METHODS: A group of rats initially received oral misoprostol treatment of 1, 10, 50 and 100 microg/kg, respectively. By using orally fed charcoal as a motility marker, the SIT was assessed at 30 min following oral misoprostol treatment. Another group of rats received misoprostol as an intraperitoneal injection in similar doses to the group above. The small intestinal transit was computed for this group at 30 min following misoprostol injection via an instilled radiochromium motility marker that went through a previously placed intraduodenal catheter. The plasma VIP level was measured by using a radioimmunoassay kit. RESULTS: Neither charcoal evaluated transit nor the plasma VIP level was influenced by the lower doses of oral misoprostol treatment (1 and 10 microg/kg), whereas other doses enhanced SIT and diminished the plasma VIP level (P< 0.01).The similar effects on radiochromium computed SIT (P< 0.01) and plasma VIP levels were obtained in tubed rats following misoprostol intraperitoneal treatment. The SIT results correlated negatively with plasma VIP levels. CONCLUSIONS: Enhanced SIT and diminished VIP levels are found in rats following misoprostol treatment. It appears that inhibited VIP release is one of the mechanisms in misoprostol-enhanced SIT.     

Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs.

The effects of loperamide (0.1 mg/kg orally) on net colonic water absorption, orocolonic transit time, and intestinal motility were investigated in pigs chronically fitted either with two cannulas in the proximal colon and a catheter in the duodenum and the ileum or with intraparietal electrodes on the duodenum, jejunum, caecum, and proximal colon and a duodenal catheter. Loperamide, given 20 minutes before a meal reduced significantly colonic net water absorption for 10 hours after eating. It also reduced colonic flow rate, increased orocolonic transit time, modified the postprandial intestinal motility by inducing supplementary phase 3 motor complexes and did not affect caecocolonic motility. Intraduodenal infusion of a hypertonic solution of mannitol (900 mOsm/l; 0.6 ml/minute) for the first postprandial hour strongly reduced or reversed net colonic water absorption, increased the colonic flow rate, accelerated the orocolonic transit, and induced profuse diarrhoea. After loperamide administration, all these effects were blocked and the relative colonic water absorption, expressed as the fraction of flow entering the colon, was strongly increased. Mannitol did not modify motility of the small and large intestine, and supplementary phase 3 motor complexes were observed when mannitol infusion was preceded by loperamide administration. It is concluded that in experimental osmotic diarrhoea loperamide causes a reduction in digesta flow entering into the colon, mediated by its action on small intestinal motility, and an increase in colonic water absorption.     

Mucosal Surface Area of a Reversed Intestinal Segment in Rats

Only scarce knowledge exists of morphologic changes after antiperistaltic reversal of the small intestine. Previous animal models using a reversed segment of the small intestine after massive intestinal resection have been mostly concerned with assessing absorption. A rat model was therefore developed for the purpose of studying mucosal surface area in the small intestine after reversal of an intestinal segment. A reversal of 10 cm, representing a length of about 10%, was found suitable for the investigation. Marked dilatation of the reversed segment occurred. A pronounced increase in mucosal surface area caused by mucosal hyperplasia was observed. The mucosal surface area in an anastomosed, but not reversed, segment also increased markedly compared with a group undergoing no operation, although less than in the reversed segment. We conclude that a reversed intestinal segment will increase mucosal surface area in an optimal length used for this purpose. This increase is possibly caused by prolonged exposure to intestinal chyme.     

Effects of enteral feedback inhibition on motility,luminal flow,and absorption of nutrients in proximal gut of minipigs

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1–4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3–13.4%) compared to the marked inhibition of the motility parameters (54–64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/6-3.     

Propulsive activity of the rat small intestine during infection with the nematode Nippostrongylus brasiliensis

Summury Intestinal propulsive motility was measured in rats infected with 4000 Nippostrongylus brasiliensis larvae by following the transit of radioactive chromium (⁵¹Cr) through the gut. On days 6, 8, 10, 12 and 14 post-infection, ⁵¹Cr was injected through an indwelling catheter into the duodenum. The animals were killed 15 min later and the distribution of radioactivity in the small intestine measured. A group of uninfected, catheterized animals served as controls. Intestinal propulsive activity was increased significantly on day 8 post-infection. No significant difference in the overall intestinal transit occurred on days 6,10,12 and 14 post-infection, although it appeared that it may have been decreased in the upper small intestine on day 6. The significance of these results is discussed.     

脑外伤大鼠肠运动功能障碍及与血清Ghrelin的关系

目的探讨创伤性脑损伤（TBI）后大鼠肠运动功能异常及其与血清Ghrelin改变的关系。方法雄性Wistar大鼠64只,随机分为两组。TBI组采用改良Feeney自由落体撞击伤法建立TBI模型;对照组只开骨窗,不行落体致伤。两组大鼠分别在致伤后3、6、12、24 h观察血清Ghrelin水平、小肠传输系数及肠黏膜病理改变。结果 TBI后各组大鼠光镜下肠黏膜上皮细胞明显受损,电镜下可见细胞连接较对照组增宽;各时间点的肠道传输系数及血清Ghrelin值均低于对照组,二者呈正相关。结论大鼠在TBI后早期即可出现小肠黏膜损伤和小肠运动功能减低,在此期间血清Ghrelin的变化可能起一定作用。     

Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion

Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion (IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the (potential) future clinical implications.     

Adaptive changes in postprandial motility after intestinal resection and bypass

An electromyographic technique was used to study the changes in postprandial motility induced by jejunal and ileal resection and jejunal bypass (50% reduction of total length of small bowel). Electrodes were implanted in rats throughout the intestine. Compared to control animals, the duration of postprandial interruption of the myoelectric complex (DIMC) was rapidly increased after jejunal resection, more gradually augmented after jejunal bypass, and remained constant after ileal resection. The frequency of occurrence of spike bursts during the postprandial period was significantly decreased in the short remaining proximal segment after jejunal resection and was not changed in the ileum. The jejunal bypass induced no change in the frequency throughout the remaining bowel. Ileal resection was followed by a decrease on the jejunum. The percentage of slow waves superimposed by a spike burst remained constant after jejunal resection and bypass but was significantly decreased after ileal resection on the whole remaining intestine. These results show important modifications in postprandial motor activity of the small bowel, which appear rapidly after jejunal resection, more gradually after jejunal bypass, and which are less pronounced after ileal resection. This electromyographic study emphasizes the role of intestinal motility in the development of adaptation after small bowel resection or bypass.     

Effect of pacing on small intestinal motor activity and hormonal response in dogs

In seven beagle dogs with a Thiry-Vella loop, the effect of pacing on small intestinal motor activity was examined by means of extraluminal strain gauge force transducers. Recordings were obtained from the loop and from the remaining small intestine. Our study showed that pacing of the loop results in a significant reduction of the motility of the loop in the overnight fasted state (up to 39%), during loop feeding (up to 55%), and oral feeding (up to 39%); a similar reduction of the motility of the remaining small intestine (up to 43%); and a significant postprandial increase of insulin (9.0 U/ml) and decrease of glucagon (94 pg/ml). The motility reduction of the loop and of the remaining small intestine as well as the anabolically improved pancreatic endocrine function (shown by an increase of the insulin — glucagon ratio) suggests that this form of pacing could be of benefit for motility disorders with decreased transit time.The present study was supported by Deutsche Forschungsgemeinschaft.     

Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

INTRODUCTION In recent years, along with the extensive research into enteric nerve system (ENS), increasing evidence shows that peptidergic neurotransmitters are the key factors regulating the gastric motility. Our previous research[1-3] showed that electroacupucture (EA) at acupoints of the Stomach Meridian of Foot-Yangmin may regulate gastric movement, increase blood flow in the microvessels in the gastric mucosa, and exert a protective effect on gastric mucosa. Nitric oxide (NO) an…     

Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

AIM： To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth （SIBO） in Nonalcoholic steatohepatitis （NASH）, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.
METHODS： Forty eight rats were randomly divided into NASH group （n = 16）, cidomycin group （n = 16） and control group （n = 16）. Then each group were subdivided into small intestinal motility group （n = 8）, bacteria group （n = 8） respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes （E. coli and anaerobes （Lactobacilli）. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.
RESULTS： Small intestinal transit was inhibited in NASH group （P 〈 0.01）. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group （P 〈 0.01）. High fat diet resulted in quantitative alterations in the aerobes （E. coli） but not in the anoerobics （Lactobacill）. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group （1.70 ± 0.12 log10 （CFU/g） vs 1.28 ± 0.07 log10 （CFU/g）, P 〈 0.01）. TNF-α concentration was significantly higher in NASH group than in control group （1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P 〈 0.01）. TNF-α concentration was lower in cidomycin group than in NASH group （0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P 〈 0.01）. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-α levels of NASH rats.
CONCLUSION： SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can allevi     

电针足三里穴对不完全性肠梗阻大鼠小肠肌电活动的影响

目的:探讨电针足三里穴对肠梗阻大鼠小肠肌电活动的影响.方法:采用非贯穿肠管的方式,末端回肠套环建立不完全性肠梗阻大鼠模型,将大鼠随机分为:空白对照组(n=10)、假手术组(n=10)、肠梗阻组(IO组,n=10)、肠梗阻+电针组(14dIO+EA组,n=10,21dIO+EA组,n=10).造模成功后空白对照组、假手术组、IO组均未给予电针治疗措施,IO+EA组连续给予电针14d、21d电针治疗措施.最后1次电针后2h,分别测体质量后打开腹腔,肉眼观察回肠组织形态学的改变,BL-420F生物机能实验系统测定回肠肌电.结果:IO组大鼠体质量较空白对照组和假手术组显著降低(P<0.01),IO+EA组大鼠体质量较IO组显著升高(P<0.01).回肠肌电慢波活动改变情况:14dIO组振幅(mV)低于空白对照组(0.11±0.03vs0.35±0.06,P<0.01),且频率(%)、振幅(%)变异系数均明显高于空白对照组和假手术组(27.71±10.54vs14.08±4.22,22.00±6.24;75.54±8.59vs15.84±1.49,20.67±7.57,均P<0.01);电针实验治疗IO+EA组大鼠14...     

Do Elevated Plasma Vasoactive Intestinal Polypeptide (VIP) Levels Cause Small Intestinal Motor Disturbances in Humans?

Increased VIP plasma levels cause severe secretory diarrhea. Moreover, VIP is a major regulator of human intestinal motility. We hypothesized that VIP-mediated intestinal motility disturbances contribute to symptoms in elevated plasma VIP. Ten healthy volunteers were intubated twice with an orojejunal multilumen tube for duodenal manometry, jejunal perfusion of electrolyte and marker solution, and aspiration 10 and 40 cm more distally. All subjects randomly received intravenous infusion of saline and 300 pmol/kg * hr VIP for 5 hr. Results showed that VIP but not saline infusion induced net jejunal sodium secretion, watery diarrhea, and cardiovascular effects (P < 0.04). VIP did not alter intestinal motor activity or the mean duration of the interdigestive motility cycle or of phases I and II but nearly halved the duration of phase III (P = 0.0002). We conclude that increased plasma VIP markedly shortens human phase III activity without influencing other motility parameters. Hence, it is unlikely that VIP-mediated small intestinal motor disturbances cause symptoms in VIPOMA. Yet VIP may contribute to terminate phase III motility.     

Effects of erythromycin in chronic idiopathic intestinal pseudo-obstruction

The prokinetic effects of erythromycin, a macrolide antibiotic, on the gastrointestinal tract as a motilin receptor agonist and its potential value for the treatment of gastrointestinal motility disorders have recently attracted interest. The effects of erythromycin on the clinical symptoms and gastrointestinal motility of patients with chronic idiopathic pseudo-obstruction have not been investigated extersively. We presented a case of chronic idiopathic intestinal pseudo-obstruction, in a 67-year-old man in whom oral erythromycin (900 mg/day) dramatically improved postprandial abdominal distention, nausea, and vomiting. Other agents with prokinetic effects on intestinal motility, i.e., cisapride, domperidone, metoclopramide, and trimebutine maleate did not have a favorable effect. Gastric emptying, measured by the sulfamethizole method; and intestinal transit, evaluated using radio-opaque markers, were markedly improved by treatment with erythromycin. Our experience suggests that the prokinetic effects of erythromycin may be of therapeutic value in chronic idiopathic intestinal pseudo-obstruction.     

模拟失重对大鼠血浆ghrelin、VIP和胃肠动力的影响

目的探讨模拟失重状态下胃肠激素ghrelin和VIP的改变以及对胃肠动力的影响。方法 32只Wistar大鼠,随机分为4组,每组8只,按模拟失重的时程分为14 d组和21 d组,并分别设立非悬吊14 d对照组和非悬吊21 d对照组。先后进行胃浆膜肌电的描记、葡聚糖蓝2000标记法测定胃残留率和小肠推进率,血浆ghrelin和VIP浓度分别用酶免法(ELISA)和放免法(RI)测定。结果悬吊14 d组与21 d组与相应对照组比较,ghrelin浓度下降VIP浓度升高,同时表现为胃肌电延缓,胃残留率增加;小肠推进率下降,差异均具有统计学意义(P<0.05)。结论模拟失重状态下血浆ghrelin下降和VIP升高可能是导致胃肠动力下降的重要因素之一。     

The Relationship Between Intestinal Hypoperfusion and Serum D-Lactate Levels During Experimental Intra-Abdominal Hypertension

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may result from several clinic situations and carries high morbidity and mortality risk, particularly in intensive care unit patients. The clinical spectrum changes from splanchnic hypoperfusion and intestinal ischemia to multiple organ failure. Previous studies demonstrated that serum D-lactate levels may be an early indicator in intestinal ischemia. This study aimed to investigate the relationship between intestinal ischemia and serum D-lactate levels during experimental IAH. Thirty-two male Wistar Albino rats weighing 250+/-50 g were divided into four groups. Three different intra-abdominal pressure (IAP) levels supplied by placement of an intraperitoneal Peritofix catheter and iso-osmotic polyethylene glycol infusion. Each of the IAP levels (15, 20, and 25 mm Hg groups) was checked with the monitor system and fixed for an hour. Control-group animals were not subjected to increased IAP. One hour later, 5-ml blood samples were taken for measurement of serum D-lactate levels and 2-cm intestinal tissue samples were taken 5 cm proximal to the ileocecal valve for histopathologic examination. Elevated serum D-lactate levels were recorded in animals with higher IAP levels.There was a positive correlation between serum D-lactate levels and IAP levels. Histological examinations of the intestinal tissue samples showed no significant pathologic changes in concordance with intestinal ischemia. Serum D-lactate levels may be an early indicator for increased IAP pressure before intestinal ischemic changes occur.     

TNF-α and plasma D(-)-lactate levels in rats after intestinal ischemia and reperfusion

Objective To study the potential role of tumor necrosis factor-or(TNF-α)induction in the development ofmucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury,and to examine whetherpretreatment with monoclonal antibody against TNF-α(TNF-αMoAb)would affect the release of D(-)-lactate afterlocal gut ischemia followed by reperfusion.Methods Anesthetized Sprague-Dawley rats underwent superiormesenteric artery occlusion for 75 min followed by reperfusion for 6 hr.The rats were treated intravenonsly with eitherTNF-α MoAb(20 mg/kg)or albumin(20 mg/kg)30 min prior to the onset of ischemia.Plasma D(-)-lactate levelswere measured in both the portal and systemic blood by an enzymatic spectrophotometrie assay.Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals.In addition,a postmortemexamination was performed together with a macropatholngical evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in boththe control and treatment groups(P<0.05).However,animals pretreated with TNF-α MoAb at 6 hr after reperfusionshowed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with thoseonly receiving albumin(P<0.05).In the control animals,a remarkable rise in intestinal TNF-α level was measuredat 0.5 hr after clamp release(P<0.01);however,prophylactic treatment with TNF-α MoAb completely annulled theincrease of local TNF-α levels seen in the control animals.Similarly,after anti-TNF-α MoAb administration,intestinalTNF-α mRNA expression was markedly inhibited,which showed significant differences when compared with the controlgroup at 0.5 hr,2 hr and 6 hr after the release of occlusion(P<0.05-0.01).In addition,the pathologicalexamination showed marked intestinal lesions that formed during ischemia,which were much worse upon reperfusion,particularly at the 6 hr time point.These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier,resulting inincreased plasma D(-)-lactate levels in both portal and systemic blood.These results suggest that TNF-α appears to beinvolved in the development of local damage associated with intestinal ischemic injury.Moreover,prophylactictreatment with TNF-α MoAb exerts preventive effects on ischemia/reperfusion-induced circulating D(-)-lactateelevation and gut injury.(J Geriatr Cardiol 2004;1(2):119-124.)