Endogenous endotoxin absorption and the role of intestinal lymphatics

We investigated the absorption routes of endotoxin derived from the intestine of rabbits with or without thoracic duct lymph drainage (TDLD). The intestinal circulatory disorders induced were superior mesenteric artery occlusion (SMAO) and superior mesenteric vein occlusion (SMVO). Detection and quantitation of endotoxin in plasma and lymph were carried out using a synthetic chromogenic substrate (peptide-4-methyl-coumarin amide, MCA). In the SMAO group, endotoxin levels in portal plasma exceeded levels in lymph from the thoracic duct throughout the experiment, and in the SMVO group, the relationship was reversed. In peripheral arterial blood, endotoxin levels were significantly lower in rabbits with TDLD than in those with intact lymphatic system. Intestinal lymphatics probably play an important role in appearance of systemic endotoxemia in non-septic shock.     

肠道缺血再灌注损伤时肠淋巴干结扎对系统炎性反应的影响

目的比较大鼠肠道缺血再灌注损伤时肠淋巴干结扎与不结扎对循环中炎性介质和细菌内毒素的影响。方法采用肠道缺血再灌注模型进行肠系膜淋巴管结扎。大鼠随机分4组，每组10只：空白组（A组）；假手术组（B组）；肠道缺血再灌注组（C组）；肠道缺血再灌注加淋巴干结扎组（D组）。缺血再灌注后，作肠系膜淋巴结培养计算细菌易位率；检测循环中内毒素、D-乳酸、二胺氧化酶、TNF—α、IL-1β、IL-6和sICAM-1水平。结果细菌易位率A、B两组为0；C组40％，D组20％。与A、B组比较，C、D两组内毒素、D-乳酸和二胺氧化酶水平显著增高（P〈0．05），且D组显著低于C组；血循环中各细胞因子除sICAM-1在D组与C组之间没有显著差异外，C组的IL-1β、IL-6和TNF-α浓度均明显高于D组（P〈0．05）。结论肠道缺血再灌注损伤时，肠淋巴干结扎可减少细菌在肠系膜淋巴结的定植，并减轻肠道缺血再灌注的损伤及增加通透性，从而减轻全身炎性反应。     

三七根总皂甙对SMAO休克家兔肝脏的保护作用

目的：观察三七皂甙治疗后对休克兔肝脏超微结构的保护作用。方法：家兔20只,随机等分为对照组与治疗组。钳夹肠系膜上动脉制成SMAO休克模型。治疗组静注三七根总皂甙200mg/kg,对照组静注等量生理盐水。结果：治疗组存活时间明显延长,并改善MAP。休克期间肝细胞的破坏明显减轻,与对照组比较肝窦内枯否氏细胞功能较为活跃。结论：三七皂甙对肝脏有保护作用,对延长SMAO休克兔的存活时间起到了重要作用。     

Effects of anti-shock agents on the re-opened superior mesenteric artery flow

We investigated intestinal blood circulation after re-opening of a fixed-time occlusion of the superior mesenteric artery (SMA) in rabbits. The SMA root was occluded for 60 minutes, after which blood pressure and SMA flow were monitored for one hundred minutes under the administration with fluid infusion of three anti-shock agents; dopamine, phenoxybenzamine and dexamethasone. The intestinal wall tissue circulation in parallel with SMA flow was also studied. Blood pressure and SMA flow decreased after release of the SMA occlusion (SMAO), as compared those during pre-occlusive time in the control group. Fluid infusion alone did not improve blood pressure and SMA flow. Pre-administration of dexamethasone with fluid infusion improved blood pressure, SMA flow and the survival rate. Phenoxybenzamine with fluid infusion improved SMA flow, despite the low blood pressure. Circulatory damage to the intestinal wall was more extensive than that to SMA flow. These findings suggest that the severity and mortality of SMAO shock was not caused by plasma loss but rather by toxic metabolites and endotoxin from the ischemic intestine.     

Ischemia-reperfusion injury following superior mesenteric artery occlusion and strangulation obstruction

BACKGROUND: Intestinal ischemia-reperfusion injury (IRI) is a serious and common clinical entity resulting in severe tissue injury. This study was designed to compare IRI in superior mesenteric artery (SMA) occlusion and strangulation obstruction (SO). MATERIALS AND METHODS: Thirty Wistar-Albino rats were assigned randomly to three groups. In the control group, a sham operation was performed. In the SMA occlusion group, a vascular clamp was placed across the SMA to occlude arterial circulation. In the SO group, a 15-cm segment of small intestine was looped to prevent venous circulation. Sixty minutes of ischemia was followed by 60 min of reperfusion. Following reperfusion, biopsies of small intestine were taken to assess morphologic damage, tissue levels of malonyldialdehyde (MDA) as an index of lipid peroxidation reflecting oxygen free radicals (OFR) were determined, and serum biochemical analyses were performed. RESULTS: The levels of tissue MDA were significantly higher in the SO group than in the SMA occlusion group (P < 0.05). Biochemical parameters of SO and SMA occlusion groups were higher than those in the control group and there was a significant difference between the SMA occlusion and the SO models, except for ALP levels. Histopathologically, transmural intestinal damage were present in seven cases of SO and in six cases in the SMA occlusion group. CONCLUSIONS: Despite no significant difference between the two groups in terms of intestinal tissue damage, OFR-induced injury was higher in the strangulation obstruction group.     

吲哚美辛治疗兔SMAO休克的作用机制及给药时机

目的:研究吲哚美辛对SMAO休克兔作用机制及给药时机。方法:32只SMAO休克兔随机均分四组:对照组(A)、夹闭时给药组(B)、松夹时给药组(C)和松夹30分给药组(D),给药组均静注吲哚美辛5mg/kg,观察休克4小时内存活情况、血动学、血钙、心肌组织钙和TXB_2与6-keto-PGF_(1α)含量,并作电镜观察。结果:用药组存活率高于对照组,血流动力学改善,血钙稳定,B、C两组心肌钙含量降低,TBX_2及6-keto-PGF_(1α)组间比较无显著性差异。心肌组织电镜显示C组病变程度最轻,A及D组最重。结论:吲哚美辛能改善SMAO休克兔血动学,延长存活时间并提高存活率;作用机制与加强心肌收缩力和钙通道阻滞作用有关,可能与前列腺素无关;给药时机,宜早期应用。     

Intrinsic endotoxemia after massive hepatectomy--effect of intra-intestinal antibiotics

It is known that intrinsic endotoxemia is caused by two main mechanisms, reticuloendothelial system dysfunction and intestinal circulatory failure. We investigated the escape of endotoxin from the intestine under occlusion of the superior mesenteric artery 3 days after 70% liver resection in rabbits. Twelve rabbits were given intra-intestinal antibiotics (Antibiotics group) and other twelve rabbits were given saline only (Control group). The results were as follows. Indocyanine green clearance and lipid clearance were deteriorated in both groups after hepatectomy but the antibiotics group showed a better clearance rate than the control group. Serum endotoxin level was elevated slightly after hepatectomy and then grossly elevated after superior mesenteric artery occlusion, but the antibiotics group showed a lower endotoxin level than that of the control group. Seventy-two hours survival rate was apparently better in the antibiotics group. From those data we conclude that the administration of intraintestinal antibiotics contributed to the maintenance of reticuloendothelial function of remnant hepatic lobe and suppressed the serum endotoxin level after superior mesenteric artery occlusion.     

Superior mesenteric artery occlusion models shock-induced gut ischemia-reperfusion

INTRODUCTION: Superior mesenteric artery occlusion (SMAO) is a simple and reproducible model of shock-induced gut ischemia/reperfusion, but some argue that it is not clinically relevant. The purpose of the current study was to compare SMAO to a standard model of controlled hemorrhage (CH) and uncontrolled hemorrhage (UH). METHODS: Rats had femoral lines and a jejunal mucosal laser Doppler placed followed by SMAO (60 min of ischemia, no resuscitation), controlled hemorrhage (40 mm Hg for 60 min, 2:1 resuscitation shed blood and lactated Ringers), or uncontrolled hemorrhage (liver injury, 3:1 resuscitation with lactated Ringers). Base deficit, lactate, and jejunal mucosal flow (as a percentage of baseline) were recorded during ischemia and for 120 min after reperfusion. Jejunal tissue was harvested for morphological evaluation. Comparison among groups was by analysis of variance (ANOVA), and significance was set at P < 0.05. RESULTS: Mucosal blood flow was similar among groups at the onset of reperfusion (CH, 16.9 +/- 5.0% versus UH, 10.9 +/- 3.1% versus SMAO, 13.9 +/- 6.2%) and during the initial period of reperfusion. By 120 min, however, flow in CH (75.4 +/- 2.5%) was significantly higher that in either UH (36.4 +/- 13.1%) or SMAO (31.7 +/- 8.4%). Histological injury was less with CH, while base deficit was significantly higher in CH at the onset of reperfusion (-24 +/- 2 versus UH, -10 +/- 3 and SMAO, -6 +/- 3 mM/L) but comparable by the end (CH, -17 +/- 4 versus UH, -16 +/- 3 and SMAO, -17 +/- 2 mM/L). CONCLUSIONS: SMAO is a clinically relevant model of shock-induced gut ischemia/reperfusion.     

急性肠系膜血管闭塞14例诊治体会

目的探讨急性肠系膜血管闭塞(acutemesentericvascularocclusion,AMVO)的早期诊断及外科治疗方法。方法回顾性总结我院2000年9月~2005年9月收治的14例AMVO,对其临床特征、外科诊断治疗方法及预后进行分析。结果14例AMVO中肠系膜上动脉栓塞(superiormesentericar-teryembolism,SMAE)8例(57.1%),肠系膜上静脉血栓形成(superiormesentericveinthrombosis,SMVT)4例(28.6%),肠系膜上动脉血栓形成(superiormesentericarterythrombosis,SMAT)2例(14.3%)。8例SMAE术前确诊2例,均手术治愈。4例SMVT确诊2例,介入治疗1例,手术3例,全部治愈。2例SMAT均手术治疗,术中明确诊断,均治愈。结论对可疑AMVO病例应尽早进行彩超、CTA、MRA或选择性肠系膜上动脉造影,以早期明确诊断;及时介入治疗,积极剖腹探查,果断切除坏死肠管行一期吻合,术中取栓、术后抗凝溶栓及支持治疗是降低患者死亡率的关键。     

Bacterial translocation to the thoracic duct in a setting of ischemia, partial resection and reperfusion of the porcine liver.

BACKGROUND/AIMS: Bacterial translocation is postulated as a risk factor in the development of a systemic inflammatory response syndrome (SIRS). Research on this topic has focused on the detection of bacteria and endotoxin in blood or mesenteric lymph nodes (MLNs). We investigated whether bacterial translocation occurs beyond the MLNs into the thoracic duct in a setting of ischemia, partial resection and reperfusion of the porcine liver. METHODS: A porcine model of severe, extra-intestinal tissue injury, consisting of prolonged hepatic ischemia and reperfusion, in combination with hemihepatectomy, was used (experimental group, n = 5 pigs). To prevent venous congestion of the gut during ischemia, a temporary portal-caval shunt was created. In 5 animals (sham group) a sham portal-caval shunt was constructed while liver ischemia, partial resection and reperfusion were not induced. Thoracic duct lymph, portal blood and systemic blood were collected, and analyzed for the presence of bacteria and endotoxin. RESULTS: In the experimental group, the incidence of bacterial translocation to the thoracic duct was significantly higher during early reperfusion compared to the sham group (5/5 animals versus 1/5 animals, p < 0.05). CONCLUSION: This study demonstrates bacterial translocation into the thoracic duct. Translocation at this level leads to direct discharge of bacteria and endotoxin into the systemic circulation and therefore, may potentially enhance the development of SIRS.     

Occlusion of superior mesenteric artery and effect of corticosteroid in dogs

In twenty dogs the effects of superior mesenteric artery occlusion (SMAO) for two hours on several conditions likely to be responsible for the lethality of animals or men following release of SMAO were evaluated with and without corticosteroid administration. Six of ten dogs without steroid treatment died from irreversible shock within 24 hours. However, ten steroid treated dogs maintained an adequate blood pressure and survived until sacrifice 24 hours after SMAO. Release of lysosomal hydrolases, metabolic acidosis, hyperkalemia or plasma loss seemed not to have exerted important effects on the fate of animals, because their differences between the groups were not significant. Hence the mechanism underlying the beneficial effects of corticosteroid administered should be sought elsewhere.     

Thoracic duct in patients with multiple organ failure: no major route of bacterial translocation.

OBJECTIVE: To determine whether translocation of bacteria or endotoxin occurred into the thoracic duct in patients with multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Translocation of bacteria or endotoxin has been proposed as a causative factor for MOF in patients without an infectious focus, although it has rarely been demonstrated in patients at risk for MOF. Most studies have investigated the hematogenic route of translocation, but it has been argued that lymphatic translocation of bacteria or endotoxin by the thoracic duct is the major route of translocation. METHODS: The thoracic duct was drained for 5 days in patients with MOF caused either by generalized fecal peritonitis (n = 4) or by an event without clinical and microbiologic evidence of infection (n = 4). Patients without MOF who were undergoing a transthoracic esophageal resection served as controls. In lymph and blood, concentrations of endotoxin, proinflammatory cytokines, and antiinflammatory cytokines were measured. RESULTS: Endotoxin concentrations in lymph and blood of patients with MOF ranged from 39 to 63 units per liter and were not significantly different from concentrations in patients without MOF. The quantity of endotoxin transported by the thoracic duct in the study group was small. In patients with MOF, low levels of proinflammatory cytokines and high levels of antagonists of these cytokines were found. CONCLUSION: This study provides evidence that translocation (especially of endotoxin) occurs into the thoracic duct. However, these data do not support the concept that the thoracic duct is a major route of bacterial translocation in patients with MOF.     

SUPERIOR MESENTERIC VEIN THROBOSIS

Superior mesenteric venous occlusion may be difficult to recognize, but is important as it carries a better prognosis than superior mesenteric arterial occlusion, and may be amenable to surgical treatment. Three successful cases treated by thrombectomy have appeared in the literature. A case of successful superior mesenteric vein thrombectomy with bowel resection is reported.     

Intestinal energy metabolism during ischemia and reperfusion

BACKGROUND. In order to evaluate acute ischemic damage in the small intestine induced by superior mesenteric artery occlusion (SMAO) and subsequent reperfusion, changes in ATP, ADP, and AMP were measured by high-performance liquid chromatography, and changes in tissue blood flow were measured (from the serosal surface) by the laser doppler flow meter in a rat model. MATERIALS AND METHODS. The superior mesenteric artery of the rat was occluded for 30, 60, 90, and 120 min and then reopened. Core temperature was maintained carefully at 37 +/- 0.3 degrees C. RESULTS. All rats that underwent 90 and 120 min of SMAO died within 2 days, but those with 30 and 60 min of SMAO survived. ATP (10.39 +/- 0.90 micromol/g dry weight), ADP (3.34 +/- 0.33), and total adenine nucleotides (TAN; 14.08 +/- 0. 86) decreased with longer SMAO times. After 30 and 60 min of SMAO followed by reperfusion, recoveries of ATP and TAN were relatively good and ADP levels remained fairly steady, but little or no recovery of these levels was observed after 90 and 120 min of SMAO followed by reperfusion. There were linear correlations between the levels of ATP and TAN after 30 min of reperfusion and the time of SMAO. Tissue blood flow levels were constant during SMAO. After reperfusion, those levels were recovered along with the SMAO periods. But recovery rates compared with control values were not related with those of ATP. CONCLUSIONs. ATP and TAN levels, particularly at 30 min after reperfusion, seemed to be in good agreement with the tissue damage and the viability of the small intestine. We propose that the measurement of these levels may be useful for the evaluation of intestinal damage and viability.     

Endotoxin: routes of transport in experimental peritonitis

A quantitative endotoxin assay was applied in this study of endotoxin transport from the infected abdomen. In rats with fecal peritonitis, extremely high concentrations were found in thoracic duct lymph (approximately 400 times higher than those found in arterial and portal vein plasma). Taking flow rates into account, the thoracic duct carries 34 ng/hour and the protal vein 49 ng/hour after 2 hours of peritonitis. Endotoxin quantities transported by the portal vein never exceed the proposed endotoxin filtrating capacity of the liver. Furthermore, the onset of systemic endotoxemia parallels the appearance of endotoxin in the thoracic duct. The hypothesis put forward is that the development of systemic endotoxemia is mainly mediated by lymphatic transport. The results also indicate that endotoxin is normally absorbed from the intestine and transported by portal blood.     

Occlusion of superior mesenteric artery and effect of corticosteroid in dogs.

In twenty dogs the effects of superior mesenteric artery occlusion (SMAO) for two hours on several conditions likely to be responsible for the lethality of animals or men following release of SMAO were evaluated with and without corticosteroid administration. Six of ten dogs without steroid treatment died from irreversible shock within 24 hours. However, ten steroid treated dogs maintained an adequate blood pressure and survived until sacrifice 24 hours after SMAO. Release of lysosomal hydrolases, metabolic acidosis, hyperkalemia or plasma loss seemed not to have exerted important effects on the fate of animals, because their differences between the groups were not significant. Hence the mechanism underlying the beneficial effects of corticosteroid administered should be sought elsewhere.     

A new approach for acute embolus occlusion of the superior mesenteric artery

Acute embolus occlusion of the superior mesenteric artery (SMA) either demonstrates a poor prognosis, or forces the patients to endure miserable postoperative dietary lives. Recently, we developed a new successful technique which reduced the length of the intestinal segment that had to be removed. The technique was as follows: (1) the distal end of the SMA was ligated to avoid perfusion of the necrotic segment, and (2) a Fogarty balloon catheter was inserted from the distal end of the SMA and then passed proximally to remove any remaining clots. Using the above-described technique on 3 cases from 1992 to 1994, we were thus able to shorten the length of the intestine that had to be removed and thereby greatly improve the patients' postoperative dietary lives.     

急性肠系膜上动脉闭塞的诊断与治疗

目的 探讨急性肠系膜上动脉闭塞的诊断与治疗.方法 对2000-2007年收治的15例急性肠系膜上动脉闭塞患者的临床资料进行回顾性分析.结果 本组15例患者中肠系膜上动脉栓塞11例,肠系膜上动脉血栓形成4例.入院后均行急诊剖腹探查术,其中2例行肠系膜上动脉取栓术,11例行肠系膜上动脉取栓加坏死肠管切除术,2例放弃手术.术后均行肝素等抗凝治疗.4例死亡,总病死率为27%.结论 对于有器质性心脏病的患者,如突然出现腹部疼痛,应警惕肠系膜上动脉闭塞的可能.早期诊断、早期行肠系膜上动脉取栓术是提高治愈率的关键.