肠缺血再灌注损伤后内毒素增敏作用及其机制的初步探讨

目的探讨肠缺血再灌注损伤（Ｉ／Ｒ）对内毒素的增敏作用及其机制。方法大鼠肠系膜上动脉阻断４５ｍｉｎ后松夹进行再灌注,静脉注射低剂量内毒素（ＬＰＳ,１５ｍｇ／ｋｇ）。观察动物多脏器功能指标及体外诱生肿瘤坏死因子（ＴＮＦ）的改变。结果Ｉ／Ｒ＋ＬＰＳ组显著加重全身血流动力学异常改变和肝、肺、肠等器官功能损害（Ｐ＜００１）。而单纯ＬＰＳ组或Ｉ／Ｒ组上述指标改变较轻或无明显异常。体外试验显示,当ＬＰＳ刺激浓度≤１０ｎｇ／ｍｌ时,抗ＣＤ１４单抗可显著抑制全血ＴＮＦ的诱生（Ｐ＜００５～００１）,且Ｉ／Ｒ组抗ＣＤ１４单抗对ＬＰＳ诱导ＴＮＦ的抑制率明显高于伤前值或假手术组（Ｐ＜００５～００１）。结论Ｉ／Ｒ可显著提高机体对ＬＰＳ攻击的敏感性,其机理与体内ＣＤ１４依赖途径的作用增强有关。     

肠缺血再灌注损伤后内毒素增敏作用及其机制的初步探讨

目的 探讨肠缺血再灌注损伤（Ｉ／Ｒ）对内毒素的增敏作用及其机制。方法 大鼠肠系膜上动脉阻断４５ｍｉｎ后松夹进行再灌注，静脉注射低剂量内毒素（ＬＰＳ，１．５ｍｇ／ｋｇ）。观察动物多脏器功能指标及体外诱生肿瘤坏死因子（ＴＮＦ）的改变。结果 Ｉ／Ｒ＋ＬＰＳ组显著加重全身血流动力学异常改变和肝、肺、肠等器官功能损害（Ｐ〈０．０１）。而单纯ＬＰＳ组或Ｉ／Ｒ组上述指标改变较轻或无明显异常。体外试验显示，当ＬＰ     

Marked increase of plasma hyaluronan after major thermal injury and infusion therapy

Hyaluronan (HYA) is an important structural element in skin and is presumably participating in regulation of the interstitial fluid volume. HYA is transported via the lymphatics from the tissues to the blood, where its concentration is normally very low. Fluid flux through the interstitium is markedly increased after thermal injury. The present study was performed to determine whether major thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep subjected to 40% BSA full-thickness scald burns, plasma HYA concentration increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than 0.01). To clarify whether this rise represented an increased "washout" of interstitial HYA, attributable either to the burn injury or the subsequent fluid therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3 times baseline. Lung lymph flow and its concentration of HYA increased, leading to an increase in the lymphatic flux of HYA to 10-20 times baseline. In peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated Ringer's markedly increased lymphatic removal of HYA. However, plasma concentrations of HYA were 3 times higher after thermal injury than following fluid challenge alone, suggesting that thermal injury per se may also increase input of HYA into the systemic circulation.     

卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。     

Endotoxemia associated with cardiopulmonary bypass

Endotoxin (lipopolysaccharide) concentrations were determined in the systemic venous blood in nine patients undergoing cardiopulmonary bypass. Lipopolysaccharide concentrations were low and stable until institution of cardiopulmonary bypass (preanesthetic concentration 0.128 +/- 0.032 ng/ml [mean +/- standard error of the mean]; prebypass level 0.136 +/- 0.03 ng/ml). After the start of bypass, the plasma concentration of lipopolysaccharide rose progressively with time to a mean value of 0.347 +/- 0.044 ng/ml (p less than 0.01), which was 0.227 ng/ml above baseline. Upon release of the aortic clamp, an additional rise in lipopolysaccharide concentration occurred after to 5 to 15 minutes to a mean value of 0.428 +/- 0.06 ng/ml (p less than 0.001) above baseline. The concentration then decayed to the baseline level 45 to 75 minutes after termination of bypass. The peak lipopolysaccharide concentration above the baseline positively correlated with both the length of bypass (r = 0.839, p less than 0.005) and the duration of aortic cross-clamping (y = 0.0030X + 0.173 r = 0.85, p less than 0.001) when flow was nonpulsatile. The peak occurred during the period of myocardial and pulmonary reperfusion. This rise in endotoxin concentration may be one of the factors responsible for the prolonged postoperative recovery seen in some patients.     

The effect of renin-angiotensin system blockade on visceral blood flow during and after thoracic aortic cross-clamping

Surgical procedures necessitating clamping of the thoracic aorta are associated with a high incidence of postoperative renal dysfunction. Plasma renin activity is elevated during and after thoracic aortic occlusion in animals. The pathophysiology of the renal dysfunction may involve the renin-angiotensin system. Blockade of the renin-angiotensin system was studied in a canine model during occlusion of the thoracic aorta. Saralasin, a competitive blocker of angiotensin II, and the converting enzyme inhibitor MK422 were studied. Sixteen animals were separated into three treatment groups: control (five animals), saralasin (five), and MK422 (six). All dogs underwent clamping of the thoracic aorta for 60 minutes. In control animals, plasma renin activity increased from 0.16 +/- 0.04 to 6.41 +/- 1.57 ng/ml/hr at 30 minutes after thoracic aortic occlusion (p less than 0.05). Thirty minutes after cross-clamp release, plasma renin activity remained 10 times greater than baseline, 1.47 +/- 0.20 ng/ml/hr (p less than 0.05). Renal blood flow was measured with 15 micron microspheres before, during, and after thoracic clamping. In control animals, renal cortical blood flow decreased during cross-clamping and remained below baseline after clamp release: baseline, 7.05 +/- 0.98 ml/gm/min (standard error of the mean); 30 min after clamp release, 3.77 +/- 0.43 ml/gm/min (standard error of the mean) (p less than 0.05). In the MK422 group, renal cortical blood flows returned to baseline after cross-clamp release: baseline, 6.38 +/- 0.49 ml/gm/min; 30 minutes after clamp release, 7.30 +/- 1.6 ml/gm/min. Infusion of MK422 after placement of the thoracic aortic cross-clamp resulted in normal renal blood flow after clamp release. This protective effect was not seen with saralasin. The resumption of normal renal cortical blood flow after the administration of the converting enzyme inhibitor MK422 suggests that elevated plasma renin activity may contribute to renal dysfunction after thoracic aortic occlusion.     

大鼠急性肠缺血后血浆D-乳酸的变化及其与肠粘膜损害的关系

目的观察肠缺血再灌注时门、体循环 D-乳酸的动态变化及其与肠粘膜损害的相关性。方法采用大鼠肠系膜上动脉阻断75分钟后松夹进行重灌注的模型,分别于术前,阻断末,松夹后0.5,2,6小时活杀动物,观察门静脉和体循环 D-乳酸水平、血浆内毒素含量及小肠病理形态学改变。结果肠缺血75分钟后大鼠门静脉 D-乳酸水平较伤前值显著上升(P<0.05),再灌注后呈进一步持续升高趋势。外周血 D-乳酸的改变与门脉血基本一致,各时相点与门脉血含量相比差异无显著意义(P>0.05)。相关分析结果显示,门静脉血浆 D-乳酸含量与肠粘膜损伤评分值呈显著正相关(r=0.415,P<0.01)。与此同时,大鼠肠缺血75分钟门静脉内毒素含量迅速上升,再灌注后2小时达峰值。结论急性肠缺血再灌注可致肠粘膜屏障破坏。使门、体循环 D-乳酸水平显著升高,其含量与小肠粘膜损害密切相关。因此,D-乳酸可作为新的血浆标志物应用于急性肠粘膜损害的早期诊断。     

Role of granulocyte-macrophage colony-stimulating factor on apoptosis induced by ischemia-reperfusion in the intestinal epithelium

BACKGROUND: To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on ischemia-reperfusion-induced apoptosis in the intestinal epithelium. METHODS: In this study, 50 male Wistar albino rats were used. After midline laparotomy superior mesenteric artery (SMA) was identified only in the sham group, while 60 min of ischemia and 2 h of reperfusion were performed in the control group. In the treatment groups, after 15, 30 and 60 min of ischemia, respectively, 1 microg/kg GM-CSF was administered subcutaneously, followed by 2 h of reperfusion. Malondialdehyde (MDA), campothecin (CAM), an indicator of DNA fragmentation, and histopathology were evaluated in the intestinal mucosa. RESULTS: Tissue MDA levels were found significantly high in all groups at various times of ischemia and 2 h of reperfusion compared with the sham group (p < 0.001). Administration of GM-CSF following 60 min of ischemia caused a significant increase in the MDA levels compared with the control group (6430 +/- 725 vs. 4174 +/- 565 nmol/g protein for jejunum. 7576 +/- 618 vs. 4938 +/- 809 nmol/g protein for ileum, p < 0.05). Intestinal ischemia and reperfusion resulted in a significant increase in tissue CAM levels (p < 0.05). The highest CAM value was found in the group in which 60 min of ischemia and 2 h of reperfusion were performed (50 +/- 3.2 ng/ml for jejunum, 52.8 +/- 2.7 ng/mg for ileum). Compared with the control group, GM-CSF administration following 1 h of ischemia aggravated the tissue injury. CONCLUSIONS: Apoptosis was induced in the small intestine by ischemia-reperfusion. GM-CSF increased the apoptosis of intestinal epithelial cells and exacerbated mucosal injury due to ischemia-reperfusion.     

The mechanisms and prevention of intravascular fluid loss after occlusion of the supraceliac aorta in dogs

Mechanisms of intravascular fluid depletion after temporary occlusion of the supraceliac aorta were investigated in a canine model. During ischemia and reperfusion, hemodynamic parameters, superior mesenteric artery flow, intestinal mucosal perfusion, and mucosal permeability were monitored. After 12 hours of reperfusion, the volumes of intravenous electrolyte fluid required to maintain hemodynamic stability and fluid lost into the gastrointestinal tract and peritoneal cavity were measured. The distribution of total body water was analyzed by use of radionuclide dilution techniques. Group A animals underwent laparotomy only, group B had the supraceliac aorta occluded for 45 minutes, group C had superoxide dismutase administered after 45 minutes of aortic occlusion, and group D animals were exposed to mild hypothermia during a similar ischemia and reperfusion period. No significant difference was found in mean superior mesenteric artery flow or mucosal perfusion during ischemia among groups B, C, and D. During reperfusion superior mesenteric artery flow returned to values similar to control in all groups. Aortic occlusion increased mucosal permeability most significantly in group B (p less than 0.01). Mean intravenous fluid requirements (ml/mg) were the following: group A, 80 +/- 5; group B, 201 +/- 9 (p less than 0.01); group C, 116 +/- 7 (p less than 0.05); group D, 245 +/- 24 (p less than 0.05). Mean gastrointestinal fluid loss was highest in the hypothermic group and smallest if superoxide dismutase was given. Mean intracellular fluid volume was increased in groups B and D compared with group A (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lower Limb Ischemia-Reperfusion Injury Triggers a Systemic Inflammatory Response and Multiple Organ Dysfunction

Restoration of blood flow to an acutely ischemic lower limb may, paradoxically, result in systemic complications and unexpected mortality. We investigated the effect of acute ischemia-perfusion of the lower limb on cytokine production and end organ function. Plasma concentrations of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were determined in five groups of male Wistar rats: control, 3 hours of bilateral hind limb ischemia alone, and 3 hours of bilateral hind limb ischemia followed by 1 hour, 2 hours, or 3 hours of reperfusion, respectively. In a second experiment, the effect of lower limb ischemia-reperfusion on remote organs (lung, liver, and kidney) was assessed biochemically and histologically. There was a significant increase in plasma concentrations of TNF-a in plasma of animals subjected to 3 hours of bilateral hind limb ischemia followed by 1 hour of reperfusion, 40.1 +/- 4.4 pg/ml, when compared with controls, 22.6 +/- 4.4 pg/ml, or animals in the ischemia-alone group, 16.3 +/- 5.2 (p <0.05). Plasma concentration of IL-6 increased progressively and significantly in animals subjected to bilateral hind limb ischemia followed by 1 hour of reperfusion, 720 +/- 107 pg/ml; 2 hours of reperfusion, 1987 +/- 489 pg/ml; or 3 hours of reperfusion, 6284 +/- 1244 (p <0.0001), compared with controls, 104 +/- 43 pg/ml; or animals in the ischemia-alone group, 140 +/- 55 pg/ml. In the study comparing portal and systemic concentrations of IL-6, systemic concentrations of IL-6, 967 +/- 184 pg/ml were significantly higher than those in the portal circulation 577 +/- 127 pg/ml (p <0.05). There was a significant increase in plasma concentrations of urea, creatinine, aspartate transaminase, alanine transaminase, and lactic dehydrogenase in reperfused animals compared with controls (p <0.001). Morbidity and mortality following reperfusion of the acutely ischemic limb may be a manifestation of multiple organ dysfunction caused by a systemic inflammatory response triggered by reperfusion of the ischemic extremities.     

大鼠急性肠缺血后血浆D—乳酸的变化及期与肠粘膜损害的关系

OBJECTIVE: To determine the kinetics of plasma D(-)-lactate levels in both portal and systemic circulations, and to examine whether elevated plasma D(-)-lactate would correlate to intestinal injury in rats subjected to acute intestinal ischemia-reperfusion. METHODS: Anesthetized rats underwent 75 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion. Plasma D(-)-lactate levels were measured by an enzymatic spectrophotometric assay. RESULTS: It showed that intestinal ischemia for 75 minutes resulted in a significant elevation in D(-)-lactate levels in portal vein blood compared to baseline values (P < 0.05). Plasma D(-)-lactate levels had a tendency to further increase after reperfusion up to 6 hours. Similar alterations in D(-)-lactate were also found in systemic circulation, there were no significant differences between the portal and systemic circulation at any time point. Moreover, the histopathological evaluation scores were significantly correlated to the portal D(-)-lactate levels in animals at various time points (r = 0.415, P < 0.01). In addition, a remarkable rise of endotoxin concentration within portal vein was already found at the end of 75-minute ischemia (P < 0.05), reaching a peak at 2 hours post-reperfusion. CONCLUSION: These data suggest that acute intestinal ischemia is associated with failure of mucosal barrier resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. The subsequent reperfusion might cause further increase in D(-)-lactate levels, which correlated to the histopathological alterations. Plasma D(-)-lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insults.     

Circulating concentrations of porcine ileal peptide but not hexosaminidase are elevated following 1 hr of mesenteric ischemia

Porcine Ileal Peptide (PIP) is located in the mucosa of the small bowel. We hypothesized that PIP may be useful as a marker for early intestinal ischemia or other acute processes of the mucosa. To test this hypothesis we developed a model of acute reversible intestinal ischemia in the pig. Following isolation of a 100-cm segment of ileum on a vascular pedicle baseline, serum and tissue samples were obtained. The vessels were then occluded for 60 min and the segment was reperfused. Serial serum samples were taken and analyzed for PIP and hexosaminidase (HEX). HEX enzyme activity in serum is known to be elevated in animals having intestinal necrosis. The Student t test for paired data was used. In preliminary studies we found that circulating HEX activity became elevated following 3 to 4 hr of vessel occlusion followed by reperfusion. In the current experiments, following 1 hr of ischemia, PIP rose significantly in the peripheral circulation, being 153.8 +/- 76.8, 909.0 +/- 150.4, and 898.3 +/- 128.1 ng/ml (P less than 0.001) at 0, 60, and 360 min after reperfusion of the segment. HEX on the other hand did not change significantly throughout the experiment, having been 766.0 +/- 28.1, 752.0 +/- 71.3, and 780.1 +/- 53.7 nM/liter (ns) at 0, 60, and 360 min following reperfusion of the segment. Histology demonstrated some clubbing, shortening and fracturing of villi with thinning of the tips of the villi in many cases. Immunospecific staining for PIP was present along the intact borders of the villi.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dantrolene in an in vivo and in vitro model of myocardial reperfusion injury

BACKGROUND: In skeletal muscle, dantrolene reduces free cytosolic calcium by inhibiting calcium release from the sarcoplasmic reticulum. A similar effect in ischemic-reperfused heart cells would protect myocardial tissue against reperfusion injury. We tested the hypothesis that dantrolene infusion during reperfusion protects the heart against reperfusion injury. METHODS: Isovolumetric beating rat hearts were subjected to 30 min of ischemia followed by 60 min of reperfusion. Left ventricular (LV) developed pressure (LVDP) and creatine kinase release (CKR) were determined as indices of myocardial performance and cellular injury, respectively. In the treatment groups, dantrolene (25 (DAN25) or 100 (DAN100) micromol l(-1)) was infused during the first 15 min of reperfusion; control hearts received the respective concentration of the vehicle (mannitol (CON25, CON100), each group n=7). To investigate the effects of dantrolene on reperfusion injury in vivo, 18 chloralose-anesthetized rabbits were subjected to 30 min occlusion and 180 min reperfusion of a major coronary artery. LV pressure (LVP), cardiac output (CO), and infarct size were determined. During the last 5 min of ischemia, nine rabbits received 10 mg kg(-1) dantrolene intravenously (DAN). Another nine rabbits received the vehicle (dimethylsulfoxide) and served as controls (CON). RESULTS: In isolated rat hearts, there was no recovery of LVDP in any group. Total CKR during 1 h of reperfusion was 845+/-76 (CON100) and 550+/-81 U g(-1) dry mass (DAN100, P<0.05). In rabbits in vivo, hemodynamic baseline values were similar between groups (CON vs. DAN: LVP, 99+/-6 (mean+/-SEM) vs. 91+/-6mm Hg, P=0.29; CO, 252+/-26 vs. 275+/-23 ml min(-1), P= 0.53). During coronary artery occlusion, LVP and CO were reduced in both groups (CON: LVP, 89+/-3%; CO, 90+/-5% of baseline values) and LVP did not recover to baseline values during reperfusion (51+/-5% (CON) vs. 67+/-7% (DAN) of baseline, P=0.10). Infarct size was 41+/-4% of the area at risk in controls and 37+/-6% in dantrolene treated hearts (P=0.59). CONCLUSIONS: Dantrolene reduced CKR, indicating an attenuation of lethal cellular reperfusion injury in isolated rat hearts. However, in the rabbit in vivo, there was no effect on the extent of reperfusion injury after regional myocardial ischemia.     

Experimental study of injury on the small intestine in acute portal vein occlusion and the following restoration of portal vein flow in rats--free radicals in the small intestine and lipid peroxidation

Free radicals in the small intestine were quantified by using an electron spin resonance spectrometer, and the amounts of TBA (thiobarbituric acid) reactants in arterial plasma, portal venous plasma and intestinal tissue were determined at the several stages. The effects of allopurinol, alpha-tocopherol, the simultaneous occlusion of superior mesenteric artery or the porto-jugular venous bypass, with the temporary occlusion of the portal vein, were also investigated. 1) Free radical concentration (mostly, semiquinones of CoQ and/or flavin in mitochondria) decreased with portal vein occlusion but showed a temporary increase at 10 sec after reperfusion. Allopurinol suppressed such temporary increase. 2) TBA reactants increased with the temporary occlusion of the portal vein. TBA reactants decreased during the portal vein occlusion with alpha-tocopherol and during reperfusion with allopurinol. Lipid peroxidation in the small intestine was also diminished by using the methods of simultaneous occlusion of the superior mesenteric artery or the porto-jugular venous bypass. In conclusion, there may be three sources for the generation of superoxide: the xanthine oxidase system, semiquinone radicals and paramagnetic metal irons. They may induce lipid a peroxidation, which accelerates the injury on the small intestine, in acute portal vein occlusion and the following restoration of portal vein flow in rats.     

大鼠急性肠缺血后血浆D-乳酸的变化及其与肠粘膜损害的关系

目的观察肠缺血再灌注时门、体循环Ｄ－乳酸的动态变化及其与肠粘膜损害的相关性。方法采用大鼠肠系膜上动脉阻断７５分钟后松夹进行重灌注的模型，分别于术前，阻断末，松夹后０．５，２，６小时活杀动物，观察门静脉和体循环Ｄ－乳酸水平、血浆内毒素含量及小肠病理形态学改变。结果肠缺血７５分钟后大鼠门静脉Ｄ－乳酸水平较伤前值显著上升（Ｐ＜０．０５），再灌注后呈进一步持续升高趋势。外周血Ｄ－乳酸的改变与门脉血基本一致，各时相点与门脉血含量相比差异无显著意义（Ｐ＞０．０５）。相关分析结果显示，门静脉血浆Ｄ－乳酸含量与肠粘膜损伤评分值呈显著正相关（ｒ＝０．４１５，Ｐ＜０．０１）。与此同时，大鼠肠缺血７５分钟门静脉内毒素含量迅速上升，再灌注后２小时达峰值。结论急性肠缺血再灌注可致肠粘膜屏障破坏，使门、体循环Ｄ－乳酸水平显著升高，其含量与小肠粘膜损害密切相关。因此，Ｄ－乳酸可作为新的血浆标志物应用于急性肠粘膜损害的早期诊断     

Effects of intermittent reperfusion during temporal focal ischemia.

There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 +/- 0.89 sq mm), 90-minute (1.08 +/- 1.02 sq mm), and 120-minute (8.72 +/- 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 +/- 3.10 sq mm), 90-minute (11.54 +/- 2.68 sq mm), or 120-minute (30.43 +/- 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair.     

Beta-enolase in blood plasma during open heart surgery--comparing with CK-MB and CA-III in blood plasma

Enolase isozyme composed of the beta subunit (alpha beta or beta beta enolase) is distributed predominantly in the heart and skeletal muscles. Concentrations of beta-enolase (beta subunit of enolase) in blood plasma samples serially taken from 18 patients, who received mitral valve replacement, were estimated by using a highly sensitive enzyme immunoassay method and compared with those of CK-MB in the same samples. Plasma beta-enolase levels, that were 6.60 +/- 3.84 ng/ml at the beginning of anesthesia, increased rapidly after reperfusion reaching the plateau more than 100 ng/ml between 2 to 12 hours, showing two peak (116 +/- 45.7 ng/ml at 4 hours and 112 +/- 48.1 ng/ml at 12 hours after reperfusion), and then decreased slowly remaining high levels even when plasma CK-MB levels became normal. The beta-enolase concentrations were significantly higher in coronary sinus samples than in arterial samples early after reperfusion. Since plasma carbonic anhydrase III, which is known to be localized only in the skeletal muscle, did not increase during the surgery, it is suggested that the major portion of elevated plasma beta-enolase levels were derived from the heart muscle. Plasma levels of beta-enolase increased as quickly as those of CK-MB after reperfusion and kept high levels longer than those of CK-MB. These results indicate that the determination of beta-enolase in plasma may be useful for estimating the myocardial damage during open heart surgery.     

Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue during cold storage and reperfusion

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 +/- 20; big-ET: 245 +/- 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 +/- 16; big-ET: 306 +/- 144 pg/mg) compared to baseline (ET: 32 +/- 13; big-ET: 185 +/- 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 +/- 26; big-ET: 163 +/- 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 +/- 3.0 pg/ml), C, (2.8 +/- 1.2 pg/ml) and D (2.6 +/- 2.0 pg/ml), compared to baseline (1.7 +/- 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.     

喂饲左旋精氨酸对烫伤大鼠肠道保护作用机制的研究

目的探讨喂饲左旋精氨酸(L-Arg)对烫伤大鼠肠道缺血再灌注损伤的作用机制。方法将66只SD大鼠随机分为正常对照组(6只,不作烫伤和其他处理)、精氨酸组(30只,烫伤后2h喂饲70g/LL-Arg,1ml/次,2次/d)和普通喂养组(30只,烫伤后喂饲等量凉开水)。检测正常对照组及两组烫伤大鼠伤后6、12、24、48、72h肠组织内皮素(ET)水平、一氧化氮(NO)含量、ET/NO比值以及血浆内毒素水平的变化,并取回肠组织标本作病理学观察。结果伤后6、12、24h,精氨酸组大鼠肠组织ET水平分别为(0.80±0.26)、(0.75±0.30)、(0.63±0.22)ng/g,低于普通喂养组(1.26±0.38)、(1.34±0.37)、(0.97±0.19)ng/g(P<0.05);其NO含量显著高于普通喂养组(P<0.01);ET/NO比值和血浆内毒素水平均低于普通喂养组(P<0.05或0.01)。病理学观察显示,精氨酸组大鼠肠黏膜损伤情况明显轻于普通喂养组。结论喂饲L-Arg可减轻烫伤大鼠肠组织缺血再灌注损伤,有利于保护肠黏膜屏障功能。其机制为喂饲L-Arg后增加了肠黏膜局部NO的含量,有助于维持ET/NO比值的稳定。     

The change of creatine kinase bb isozyme in patients undergoing mitral value replacement--comparison with creatine kinase MB and MM isozymes

By using highly sensitive enzyme immunoassay method recently developed, concentrations of the three forms of cytoplasmic creatine kinases (CK-BB, CK-MB and CK-MM) were determined in blood plasma samples serially taken from 18 patients, who received mitral valve replacement. Plasma CK-BB levels, that were 0.64 +/- 0.32 ng/ml at the beginning of anesthesia, increased sharply after reperfusion reaching peak levels (23.3 +/- 7.56 ng/ml) at 2 hours after reperfusion, and then decreased rapidly. The response of CK-BB in plasma was more rapid and sensitive than that of CK-BB or CK-MM. The CK-BB concentrations were significantly higher in coronary sinus samples than in arterial samples. These results suggest that the major portion of elevated plasma CK-BB levels at early phase after reperfusion were considered to be derived from the heart muscle.