Hypertonic saline resuscitation after mesenteric ischemia/reperfusion induces ileal apoptosis

BACKGROUND: We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury. METHODS: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/kg of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot. RESULTS: SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL. CONCLUSION: HS resuscitation after mesenteric I/R significantly increased ileal mucosal apoptosis while decreasing mucosal injury and may represent a novel mechanism by which HS resuscitation after mesenteric I/R reduces inflammation and imparts protection to the gut.     

Effect of intravenous glucagon on the survival of rats after acute occlusive mesenteric ischemia

The purpose of this study was to determine the optimal timing of intravenous glucagon infusion for the treatment of acute occlusive mesenteric ischemia. The superior mesenteric artery (SMA) was occluded for 85 min in 106 Sprague-Dawley anesthetized rats. The animals were divided into 12 treatment groups according to the timing of glucagon and saline administration, and survival was measured to 48 hr. Without treatment, all rats died within 24 hr. Intravenous saline (10 ml/kg/hr) for 2 hr did not significantly improve 48-hr survival (17-33%). Glucagon (1.6 micrograms/kg/min iv) plus saline (10 mg/kg/hr iv) for 2 hr after SMA occlusion significantly improved survival from 33% (saline control) to 83% (P less than 0.02). The same treatment begun 1 hr before SMA release (during ischemia) did not significantly improve survival (33% at 48 hr). Glucagon infusion during occlusive mesenteric ischemia was detrimental when added to effective postischemia treatment, reducing survival from 83 to 33% (P less than 0.02). Adequate saline infusion was required for glucagon efficacy after ischemia, as shown by an intermediate 48-hr survival of 50% when only maintenance saline (1.5 ml/kg/hr) was given. These data suggest that glucagon therapy should be delayed until after operative release of an acute SMA occlusion and should be accompanied by vigorous volume expansion.     

还原型谷胱甘肽预处理对肝脏缺血-再灌注后糖代谢的影响

目的 观察还原型谷胱甘肽(GSH)预处理对肝脏缺血-再灌注损伤(HIRI)后糖代谢的影响.方法 78只SD大鼠随机均分为假手术组(C组)、缺血-再灌注组(IR组)和GSH预处理组(G组).IR组和G组大鼠制作HIRI模型,C组仅开腹,不阻断肝门血管.每组分别在HIRI后2、6 h各取8只大鼠检测超氧化物歧化酶(SOD)、丙二醛(MDA)、血糖和胰岛素的含量,另取5只大鼠做高血糖钳夹试验后检测胰岛素含量,并计算葡萄糖代谢率(GMR)和胰岛素敏感指数(ISI).结果 与IR组比较,C组和G组血糖、MDA含量明显降低(P<0.05),胰岛素、SOD含量明显升高(P<0.05).高血糖钳夹试验后,与IR组比较,C组和G组胰岛素含量,GMR及ISI均明显升高(P<0.05).结论 GSH预处理可改善HIRI后的高血糖,其机制可能与GSH减轻HIRI过程中的氧化还原反应有关.     

肝脏缺血再灌注后急性肺损伤的机制及丙泊酚对其的保护作用

目的 观察肝脏缺血再灌注后急性肺损伤的发病机制及丙泊酚的保护作用.方法 成年封闭群SD雄性大鼠48只,采用随机数字表法随机分为:假手术组(Sham):假手术2 h(Sham2)组;假手术6 h(Sham6)组;缺血再灌注组(IR):缺血再灌注2 h(IR2)组;缺血再灌注6 h(IR6)组及丙泊酚组(P):丙泊酚2 h...     

Contemporary management of acute mesenteric ischemia: Factors associated with survival

PURPOSE: Acute mesenteric ischemia (AMI) is a morbid condition with a difficult diagnosis and a high rate of complications, which is associated with a high mortality rate. For the evaluation of the results of current management and the examination of factors associated with survival, we reviewed our experience. METHODS: The clinical data of all the patients who underwent operation for AMI between January 1, 1990, and December 31, 1999, were retrospectively reviewed, clinical outcome was recorded, and factors associated with survival rate were analyzed. RESULTS: Fifty-eight patients (22 men and 36 women; mean age, 67 years; age range, 35 to 96 years) underwent study. The cause of AMI was embolism in 16 patients (28%), thrombosis in 37 patients (64%), and nonocclusive mesenteric ischemia (NMI) in five patients (8.6%). Abdominal pain was the most frequent presenting symptom (95%). Twenty-five patients (43%) had previous symptoms of chronic mesenteric ischemia. All the patients underwent abdominal exploration, preceded with arteriography in 47 (81%) and with endovascular treatment in eight. Open mesenteric revascularization was performed in 43 patients (bypass grafting, n = 22; thromboembolectomy, n = 19; patch angioplasty, n = 11; endarterectomy, n = 5; reimplantation, n = 2). Thirty-one patients (53%) needed bowel resection at the first operation. Twenty-three patients underwent second-look procedures, 11 patients underwent bowel resections (repeat resection, n = 9), and three patients underwent exploration only. The 30-day mortality rate was 32%. The rate was 31% in patients with embolism, 32% in patients with thrombosis, and 80% in patients with NMI. Multiorgan failure (n = 18 patients) was the most frequent cause of death. The cumulative survival rates at 90 days, at 1 year, and at 3 years were 59%, 43%, and 32%, respectively, which was lower than the rate of a Midwestern white control population (P <.001). Six of the 16 late deaths (38%) occurred because of complications of mesenteric ischemia. Age less than 60 years (P <.003) and bowel resection (P =.03) were associated with improved survival rates. CONCLUSION: The contemporary management of AMI with revascularization with open surgical techniques, resection of nonviable bowel, and liberal use of second-look procedures results in the early survival of two thirds of the patients with embolism and thrombosis. Older patients, those who did not undergo bowel resection, and those with NMI have the highest mortality rates. The long-term survival rate remains dismal. Timely revascularization in patients who are symptomatic with chronic mesenteric ischemia should be considered to decrease the high mortality rate of AMI.     

Early diagnosis of acute mesenteric ischemia after cardiopulmonary bypass

BACKGROUND: The aim of this study is to identify significant risk factors and eventual clinical markers associated with acute mesenteric ischemia (AMI) after cardiopulmonary bypass. METHODS: The study was retrospectively performed on a group of 19 patients (group A) undergoing cardiac surgery between January 1991 and December 1999, who developed AMI within 30 days of their hospitalization. A control group of 48 patients (group B) was compared in order to define preoperative and operative risk factors for AMI. RESULTS: At the abdominal operation, a non-occlusive mesenteric ischemia was found in every case. In-hospital mortality was 84.2% (16/19). Compared to the control, there was a significant difference in aortic cross-clamp time (p<0.001) and use of inotropic drugs (p<0.01). Postoperatively, the studied group (group A) had a significantly higher mean value of the enzymatic serum levels at any time. CONCLUSIONS: A high index of suspicion for mesenteric ischemia after cardiopulmonary bypass should be considered in patients with conditions of hypoperfusion. The early laboratory signs of AMI might be searched during the first postoperative hours.     

Nonocclusive acute mesenteric ischemia

The authors present one case of acute mesenteric ischemia appeared to the patient 70 years old, with HTA and coronary heart disease with heart arrhythmia treated with angiotensin-converting-enzyme inhibitor, anti arrhythmia agents and antithrombin therapy (trombostop). Acute mesenteric ischemia is not an isolated clinical entity, but a complex of diseases, including acute mesenteric arterial embolus and thrombus, mesenteric venous thrombus and nonocclusive mesenteric ischemia. These diseases have common clinical features caused by impaired blood perfusion of the intestine, bacterial translocation and systemic inflammatory response syndrome. Reperfusion injury is another important feature of nonocclusive mesenteric ischemia. We discuss about the nonocclusive mesenteric ischemia is the most lethal form of acute mesenteric ischemia because of the poor understanding of its pathophysiology and its nonspecific symptoms, which often delay its diagnosis. Although acute mesenteric ischemia is still lethal and in-hospital mortality rates have remained high over the last few decades, accumulated knowledge on this condition is expected to improve its prognosis.     

金属硫蛋白与皮瓣缺血预处理延迟保护作用的实验研究

目的：探讨金属硫蛋白（MT）参与皮瓣缺血预处理（PC）延迟保护作用（DP）的可能性。方法：在猪背阔肌岛状皮瓣PC和培养肌细胞PC的模型上，检测PC后即刻，12h和24h MT含量变化，观察PC后24h对再次长时间缺血再灌注（I／R）或缺氧复氧（A／R）损伤的保护作用以及用丝裂素蛋白激酶抑制剂（PD098059）抑制PC后MT含量增高对PC和DP的影响。结果：MT含量在PC后12h（肌细胞）和24h（肌细胞和皮瓣组织）显著增高，与未PC的皮瓣组织或肌细胞遭受I／R或A／R的损伤相比较，PC后24h其皮瓣坏死范围缩小（P＜0．05），血浆乳酸脱氢酶（LDH）活性降低（P＜0．05），肌细胞存活率增高，细胞丙二醛（MDA）含量和LDH释放均降低（P＜0．01）。用PD098059抑制后则消除了PC后的DP作用，上述皮瓣损伤指标接近单纯I／R组或A／R组（P＞0．05）。结论：①PC后24h对皮瓣或肌细胞的再次I／R或A／R损伤具有保护作用；②MT参与了皮瓣或肌细胞PC后的DP作用。     

The effect of hypericum perforatum on kidney ischemia/reperfusion damage

It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague–Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR?+?HP Group which was treated with 50?mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p?p?相似文献   

阿魏酸钠对移植皮瓣缺血再灌注损伤保护的实验研究

目的：通过建立大鼠皮瓣移植损伤的动物模型,观察阿魏酸钠对皮瓣存活率的影响。方法：利用H＆E染色分析皮瓣的损伤程度,利用免疫组化检测皮瓣组织中COX-2及HO-1的表达水平,利用ELISA法检测皮瓣组织中MPO、MDA、NO的含量以及外周血中TNF-α的表达水平。结果：在移植皮瓣缺血再灌注损伤模型中,相比于生理盐水处理组,阿魏酸钠处理可显著提高皮瓣的存活率,同时上调皮瓣组织中HO-1的表达水平,抑制COX-2通路的活化。在阿魏酸钠的作用下,皮瓣组织的MPO、MDA的含量明显下降,同时NO的合成增加,阿魏酸钠可显著抑制外周血中TNF-α的表达水平。结论：阿魏酸钠对移植皮瓣缺血再灌注损伤具有明显的保护作用,其作用机制与减少炎症反应,抑制氧化应激损伤密切相关。     

Management of acute mesenteric ischemia

Acute mesenteric ischemia is a serious illness requiring prompt surgical attention. The clinical presentation, diagnostic strategy, and management of this disease are reviewed. Options for revascularization are briefly outlined.     

Hemodynamic effects of glucagon after acute mesenteric ischemia in rats

We have previously shown that iv glucagon improved survival in rats from 33 to 83% when given after, but not during, superior mesenteric artery (SMA) occlusion. This study investigated potential hemodynamic mechanisms of this effect. In Part 1, cardiac output (CO) was measured in 12 male Sprague-Dawley rats with an electromagnetic flow-probe that had been placed around the ascending aorta 5 days previously. Under pentobarbital anesthesia, the SMA was occluded for 85 min. All rats received normal saline (NS, 15 ml/kg/hr) for 1 hr before and after SMA declamping. Control rats (n = 6) received only NS. Treated rats (n = 6) received NS plus glucagon (1.6 micrograms/kg/min iv) for 1 hr postocclusion. CO decreased 50% during the first hour after SMA declamping in control rats, but only 11% in glucagon-treated rats (P less than 0.02). Systemic vascular resistance (SVR) increased by 90% in control rats by 1 hr after declamp, but only 9% in glucagon rats (P less than 0.04). Systemic blood pressure and heart rate were not different in the two groups. In Part 2, relative distribution of visceral blood flow was measured with radiolabeled microspheres injected in the aortic root before clamping, before declamping, and 1 hr postdeclamping in 10 rats (5 glucagon, 5 control) using the above protocol. After SMA clamping, the proportion of visceral blood flow distributed to the intestine fell from 45 to 20% (P less than 0.05). During reperfusion, the proportion of intestinal flow exceeded baseline (P less than 0.05), but was not different in control (64%) and glucagon-treated rats (56%).(ABSTRACT TRUNCATED AT 250 WORDS)     

���Գ�ϵĤѪ�ܹ�Ѫ��ȫ����Ϻ�����

目的 探讨急性肠系膜血管供血不全的诊断和治疗。方法 对1972年11月至1999年10月经治的20例急性肠系膜血管供血不全的临床资料进行回顾性分析。结果 该病多为高龄，常伴有心血管疾病和发生绞窄性肠梗阻，病死率很高（本组为45%）。结论 充分认识该病，选用恰当的检查技术，早期诊断，及时手术，是提高急性肠系膜血管供血不全治疗效果的关键。     

1-磷酸鞘氨醇与肺缺血/再灌注损伤

背景1-磷酸鞘氨醇(sphingosine-1 -phosphate,S1P)是鞘脂的代谢产物,不仅与细胞表面特定受体(S1PR1-5)结合产生多种生物学效应,还作为细胞内第二信使发挥作用。S1P在细胞增殖、移动、凋亡及心血管系统、免疫系统等方面都有重要的调节作用,因而参与到生物体内许多生理和病理过程。目的现就近年来的...