Induction of adhesion molecule expression in liver ischaemia-reperfusion injury is associated with impaired hepatic parenchymal microcirculation

BACKGROUND: Activated neutrophils may be important mediators in liver ischaemia-reperfusion injury (I/R). Adhesion of leucocytes to the endothelial cell surface is a result of activation of cell adhesion molecules. The aim of this study was to investigate the effect of I/R on the hepatic microcirculation (HM) and intercellular adhesion molecule (ICAM) 1 expression. METHODS: Four groups of six Sprague-Dawley rats underwent laparotomy for liver exposure. Group 1 acted as controls, and groups 2-4 underwent partial liver ischaemia for 30, 45 and 60 min respectively followed by reperfusion for 60 min. Flow in the HM was measured by laser Doppler flowmetry. Liver biopsies were taken at the end of the reperfusion period. ICAM-1 expression was assessed by immunohistochemistry (graded 0-3). RESULTS: Mean flow in the HM was significantly reduced with I/R (mean(s.e.m.) red cell flux 140(21), 52(3) and 43(2) with 30, 45 and 60 min ischaemia compared with control 230(17); all P < 0.001). ICAM-1 expression was significantly induced (mean(s.e.m.) 1.30(0.21), 2.50(0.22) and 2.80(0.17) with 30, 45 and 60 min ischaemia versus control 0.50(0.22); all P < 0.001). CONCLUSION: I/R produced a significant upregulation of ICAM-1 expression which correlated with impaired flow in the HM.     

Altered plasma melatonin concentrations after administration of propofol in continuous infusion

OBJECTIVE: To determine possible variations in plasma levels of melatonin in patients sedated with propofol administered in continuous infusion. PATIENTS AND METHODS: Healthy patients receiving spinal anesthesia for lower limb orthopedic surgery were randomized to 2 groups in this prospective study: group A patients were sedated with intravenous propofol infused at a rate of 3 to 4 mg kg(-1) h(-1) and group B underwent surgery without sedation. Data from these groups were compared with data from 2 other groups. Group C data, from healthy volunteers who did not undergo surgery or sedation, were compared with baseline values. Group D data were theoretical reference values for plasma melatonin levels taken from the literature, for comparisons at baseline and in the range of hypnosis. Hormone levels were determined by enzyme-linked immunosorbent assay at baseline, at 10 and 60 minutes after the start of sedation, and 90 minutes after withdrawal of sedation. RESULTS: Twenty patients were enrolled. No significant between-group differences were detected at baseline (P>.269), 60 minutes after starting sedation or 90 minutes after withdrawing it (P>.347 and P>.057 respectively). Values were significantly different between group B and groups A and D 10 minutes after starting sedation with propofol (P<.001). CONCLUSIONS: Plasma levels of melatonin increased during administration of propofol in continuous perfusion.     

Neurocognitive functions after beating heart mitral valve replacement without cross-clamping the aorta

BACKGROUND AND AIM OF THE STUDY: Although neurologic outcome after cardiac surgery is well-established, neurocognitive functions after beating heart mitral valve replacement still needs to be elucidated. The aim of this study was to compare preoperative and postoperative neurocognitive functions in patients who underwent beating heart mitral valve replacement on cardiopulmonary bypass without cross-clamping the aorta. METHODS: The prospective study included 25 consecutive patients who underwent mitral valve replacement. The operations were carried out on a beating heart method using normothermic cardiopulmonary bypass without cross-clamping the aorta. All patients were evaluated preoperatively (E1) and postoperatively (at sixth day [E2] and second month [E3]) for neurocognitive functions. RESULTS: Neurologic deficit was not observed in the postoperative period. Comparison of the neurocognitive test results, between the preoperative and postoperative assessment for both hemispheric cognitive functions, demonstrated that no deterioration occurred. In the three subsets of left hemispheric cognitive function test evaluation, total verbal learning, delayed recall, and recognition, significant improvements were detected at the postoperative second month (E3) compared to the preoperative results (p = 0.005, 0.01, and 0.047, respectively). Immediate recall and retention were significantly improved within the first postoperative week (E2) when compared to the preoperative results (p = 0.05 and 0.05, respectively). CONCLUSIONS: The technique of mitral valve replacement with normothermic cardiopulmonary bypass without cross-clamping of the aorta may be safely used for majority of patients requiring mitral valve replacement without causing deterioration in neurocognitive functions.     

Intestinal ischaemia-reperfusion increases plasma amylin concentration in rats

Intestinal ischaemia-reperfusion and hyperamylinaemia are both associated with severe acute pancreatitis. The aim of this study was to examine the relationship between intestinal-ischaemia reperfusion and plasma amylin in an experimental model. Wistar rats (n = 24, 400-450 g) were divided into three groups: (1) a sham (S)-operated group (n = 7) that underwent laparotomy and isolation (without clamping) of the superior mesenteric artery, (2) an ischaemia-reperfusion (IR) group (n = 7) that had clamping of the superior mesenteric artery for 60 min followed by 15 min reperfusion, and (3) a control (C) group (n = 10) that underwent no surgery. Amylin was significantly elevated in the IR group (median 39 pM, range 30-44) compared with the S group (19 pM, range 15-45; Mann-Whitney U, p < 0.05) and the C group (24 pM, range 15-55; p < 0. 01). Insulin was significantly elevated in the IR group (2,060 pM, range 1,000-4,650) compared with the S group (558 pM, range 424-2, 020; p < 0.01). There was a significant positive correlation between amylin and insulin (R = 0.82, F = 46.6, p < 0.0001), but not between amylin and glucose or insulin and glucose. Intestinal histology was consistent with an ischaemia-reperfusion injury, whereas pancreatic histology was normal. The unique finding that plasma amylin concentration is increased with intestinal ischaemia-reperfusion injury warrants further investigation.     

General anaesthesia for surgery can influence circulating melatonin during daylight hours

Background: Both melatonin and anaesthetics have been shown to affect sleep and behaviour. The effect of general anaesthesia on circulatory melatonin has not been reported, but anaesthetic-related alterations in hormone profiles are known. We hypothesize that differences in recovery from anaesthesia may be associated with differences in circulatory melatonin levels because of melatonin's sedative effect in humans. Methods: The influences of general anaesthesia and surgery on circulating melatonin, prolactin, and Cortisol concentration were investigated in 32 female patients scheduled for elective gynaecological surgery to study differences in hormone profiles and responses during anaesthesia and the recovery period. Patients were randomly assigned to one of two groups. General anaesthesia was induced with either thiopentone/fentanyl (Group 1: n=16) or propofol/fentanyl (Group 2: n=16). Maintenance of anaesthesia was achieved with either isoflurane (0.8–1.0 vol%)/fentanyl (Group 1) or propofol (6 mg · kg^?1· h^?1)/fentanyl (Group 2) with a N₂O/O₂ flow ratio of 2:1 in both groups. During anaesthesia, patients' eyes were carefully taped shut to prevent light effects. Blood samples were taken before and after premedication, immediately before induction of anaesthesia, every 15 min during anaesthesia, and hourly in the recovery room for 8 h. The control group consisted of 6 healthy women who were not subjected to surgery, but who were in a similar environment, including light conditions, as the study groups. Results: Isoflurane and propofol anaesthesia as well as darkness elicited elevated plasma melatonin levels that persisted in the recovery period in patients anaesthetized with isoflurane, but gradually decreased during the recovery of patients anaesthetized with propofol. Circulating prolactin and Cortisol values were also elevated during anaesthesia and had similar decreases during the recovery period. Conclusion: Higher plasma levels of melatonin during the recovery period following isoflurane anaesthesia may, in part, explain increased sedation in these patients compared with patients who received propofol anaesthesia. However, the relationship between recovery from anaesthesia and plasma melatonin levels may not be simple and straightforward.     

IL-8, IL-6 and ICAM-1 in serum of paediatric patients undergoing cardiopulmonary bypass with and without cardiocirculatory arrest

BACKGROUND: The aim of the present study was to evaluate the systemic inflammatory response to CPB in paediatric patients undergoing surgical correction of congenital heart diseases. METHODS: Experimental design: comparative investigation. Setting: paediatric cardiology hospital Intervention: ICAM-1, IL-8, and IL-6 production were analysed before and during CPB, and after surgery in 9 paediatric patients, submitted to cardiocirculatory arrest (Group A); and in 11 without cardiocirculatory arrest (Group B). Measures: ICAM-1, IL-8, and IL-6 production were analysed from arterial samples before and during CPB, and after surgery. RESULTS: In group A vs group B a significant increase of IL-8 was detected during (297+/-250 vs 11+/-19 pg x ml(-1), p<0.001) and after (100+/-230 vs n.d. pg x ml(-1)) surgery and was correlated with the duration of operation (r=0.759; p=0.0001) and clamping time (r=0.738; p<0.05). After surgery in group A, IL-6 levels (35+/-43 pg x ml) were higher than those in group B (2+/-5 pg x ml), and a good correlation was observed between IL-6 and duration of aortic clamping (r=0.714; p=0.048), cardiac arrest, (r=0.714; p=0.048), and length of surgery (r=0.867; p=0.04). CONCLUSIONS: In children who underwent CPB with cardiocirculatory arrest cytokine production seems related to duration of operation and amplified by ischemia-reperfusion phenomena.     

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function

BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+/-46% vs. 91+/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+/-46% vs. 129+/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+/-3.7 vs. 43+/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+/-0.4 vs. 2.6+/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+/-3.3 vs. 116+/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+/-0.3 vs. 2.6+/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.     

肠缺血-再灌注大鼠不同组织ICAM-1表达的规律

目的:了解肠缺血-再灌流过程中不同脏器 ICAM-1表达的时间、空间规律。方法:用 RT-PCR 和免疫组化的方法检测肠缺血-再灌流大鼠肠、肝和肺组织中 ICAM-1mRNA 和蛋白表达的变化。结果:肠组织中的ICAM-1 mRNA 和蛋白在肠缺血期及再灌流1h 表达增加,肝脏和肺脏毛细血管内皮上的 ICAM-1表达增加在再灌流后2h 和6h,晚于肠组织,并且与组织中性白细胞的聚集增加一致。结论:肠缺血-再灌流大鼠不同组织的ICAM-1表达的变化呈现序贯性。     

Protective effects of dexmedetomidine on ischaemia-reperfusion injury in an experimental rat model of priapism

The study aimed to investigate the effects of dexmedetomidine against ischaemia-reperfusion injury occurring after priapism in a model of induced-priapism in rats. A total of 18 male rats were randomised into three groups. Group 1 was the control group. A priapism model was performed rats in Group 2 and then ischaemia-reperfusion injury was evaluated. Group 3 had similar procedures to the rats in Group 2. Rats in Group 3 additionally had 100 μg/kg dexmedetomidine administered intraperitoneally immediately after reperfusion. Blood and tissue samples were analysed. Biochemical analysis of blood samples revealed a decrease in the levels of the pro-inflammatory cytokines including interleukin-1 beta (IL-1 Beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) in Group 3 compared to Group 2 (p:.04, p:.009 and p:.009, respectively). Similarly, the highest malondialdehyde (MDA) level was in Group 2 (p:.002). The levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were significantly higher in Group 3 than that of Group 2 (p:.037 and p:.045, respectively). Direct microscopic examinations revealed positive changes in desquamation, oedema, inflammation and vasocongestion scores in Group 3 compared to Group 2 (p:.007, p:.008, p:.007 and p:.006, respectively). Dexmedetomidine has a protective effect against ischaemia-reperfusion injury in penile tissue.     

Influence of ischemic preconditioning and blood cardioplegia protection on postischemic endothelial activation in coronary bypass surgery

Summary Background Hypothermic ischemia in open heart surgery and cardiopulmonary bypass involve a postischemic in-flammatory reaction caused by an activation of leukocytes and endothelia with the systemic release of cytokines and adhesion molecules. The present study addresses the question, if an amelioration of postischemic endothelial activation in the heart could be achieved by means of cardioplegic protection or ischemic preconditioning. In a randomized prospective study patients underwent a normothermic preconditioning procedure either followed by crystalloid or blood cardioplegia during coronary bypass surgery. Methods Patients (n=28) were included and randomized in the study according to defined criteria: Group A received St. Thomas cardioplegia, group B cold blood cardioplegia. Ischemic precon-ditioning was performed twice at normothermia under a cardiopulmonary bypass (CPB) for 5 min followed by 10 min of reperfusion before coronary aortic bypass graft (CABG) using St. Thomas (group C) or blood cardioplegia (group D) hypothermic protection. In coronary sinus blood and arterial blood myocardial (creatine-kinase myoglobin [CK-MB]) and endothelial activation (endothelin, IL-6, IL-8, sE-selectin, soluble vascular adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1]) parameters were investigated 1, 3, 6, 9, 12, and 24 h after coronary reperfusion. Results 1) Parameters of myocardial injury (CK-MB, myoglobin) revealed increased levels at 1 h and 9 to 12 h after CABG. Levels at 12 h were lower in group B and D as compared to A and C. 2) Cytokines (IL-6, IL-8) showed increased levels 3 h after reperfusion with no difference between study groups. 3) Soluble adhesion molecules (E-selectin, VCAM-1, ICAM-1) were found increased in all groups 6 to 12 h after reperfusion. Lower levels were present in group D for E-selectin and VCAM-1. Conclusions The results indicate a sequence of cytokine and adhesion molecule release as a potential pathomechanism of myocardial reperfusion injury. Gradual decrease in the release of endothelial adhesion molecules in late myocardial injury was noted for blood cardioplegia and ischemic preconditioning. Amelioration of endothelial activation by means of preconditioning and blood cardioplegia may improve heart muscle recovery in open heart surgery with borderline ischemia time and organ dysfunction.      

Post-hemorrhagic shock mesenteric lymph activates human pulmonary microvascular endothelium for in vitro neutrophil-mediated injury: the role of intercellular adhesion molecule-1

BACKGROUND: Splanchnic hypoperfusion is believed to be central in the pathogenesis of hemorrhagic shock-induced acute respiratory distress syndrome and multiple organ failure. Our previous work focused on the portal circulation as the conduit for gut-derived mediators of acute respiratory distress syndrome. Our current focus is the proinflammatory effects of postshock mesenteric lymph. We hypothesize that postshock lymph induces neutrophil (PMN)-mediated endothelial cell damage in an intercellular adhesion molecule-1 (ICAM-1)-dependent fashion, and devised a two-insult model to test this hypothesis. METHODS: Rats (n > or = 5) underwent hemorrhagic shock (mean arterial pressure, 40 mm Hg for 30 minutes) and resuscitation (shed blood plus two times crystalloid) with lymph collection. Human pulmonary microvascular endothelial cells (HMVECs) were divided into three groups and grown to near confluence. Group 1 was incubated for 6 hours in 1% preshock or postshock lymph and ICAM-1 was measured by flow cytometry. Group 2 consisted of coculture of HMVECs and PMNs after endothelial cell activation to determine whether postshock lymph would stimulate PMN adherence. Group 3 was incubated under identical conditions, but PMNs were added for 30 minutes, and then activated with 4.5 micromol/L lysophosphatidylcholine (lyso-PC) for 1 hour to ascertain cytotoxicity. HMVEC density was measured using microscopy and recorded as HMVECs per millimeter squared. ICAM-1-blocking antibody and isotype control were used to assess the effects of ICAM-1 on PMN cytotoxicity. A buffer control was used for comparison using analysis of variance with Tukey's correction. RESULTS: Postshock lymph activated HMVECs for increased surface expression of ICAM-1 and stimulated PMNs to adhere to endothelial cell monolayers. Activation of PMNs with lyso-PC in the presence of postshock lymph resulted in marked HMVEC death. The addition of an ICAM-1-blocking antibody abrogated this effect. Neither postshock lymph alone (758 +/- 35 HMVECs/mm(2)), nor postshock lymph in the presence of quiescent PMNs alone (734 +/- 28 HMVECs/mm(2)), nor lymph plus lyso-PC (834 +/- 21 HMVECs/mm(2)) provoked endothelial cell damage. CONCLUSION: Postshock mesenteric lymph activates endothelial cells for increased ICAM-1 expression and PMN adherence. Furthermore, postshock lymph acts as an inciting event in a two-event in vitro model of PMN-mediated endothelial cell injury. These findings further substantiate the key mechanistic role of mesenteric lymph in hemorrhagic shock-induced acute lung injury and suggest that ICAM-1 expression is pivotal in the two-event model of multiple organ failure.     

Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion

BACKGROUND: Inducible nitric oxide synthase (iNOS) activity is increased in experimentally induced acute pancreatitis. Increased expression of this isoform of nitric oxide synthase has been demonstrated in several organs subjected to ischaemia-reperfusion injury. The present experiment investigated the expression of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia-reperfusion. METHODS: Wistar rats (n = 40) were randomly and equally assigned to four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation. The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was administered to groups 3 and 4. Expression of iNOS was examined by immunohistochemistry. Other investigations included measurement of serum amylase activity and pancreatic wet : dry weight ratio, and histopathological examination. RESULTS: Eight of ten rats in group 2 (I-R only) expressed iNOS but none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L-NIL) animals had significantly lower serum amylase levels and wet : dry weight ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic injury was present only in rats in group 2 (I-R only). CONCLUSION: Expression of iNOS during reperfusion following pancreatic ischaemia contributes significantly to the development of acute pancreatitis.     

Propofol and tourniquet induced ischaemia reperfusion injury in lower extremity operations

BACKGROUND AND OBJECTIVE: Extremity surgery with tourniquet to provide a bloodless field may be a good human model for ischaemia reperfusion (IR) injury. The aim of this study was to investigate the effects of three different modes of propofol use on tourniquet induced IR injury in lower extremity operations. METHODS: Thirty-three consecutive ASA Grade I and II patients were randomized into three groups of 11 patients each. In the spinal group (Group S), after intrathecal anaesthesia, sedation was given with a propofol infusion at 2 mg kg-1 h-1 after a 0.2 mg kg-1 bolus dose and fentanyl 100 microg. In the general (Group G) and TIVA (Group T) groups, general anaesthesia was induced with propofol 2 mg kg-1 with fentanyl 100 microg and maintained with inhalation of halothane or infusion of propofol respectively. Venous blood samples were obtained at different time points for measurements of plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. RESULTS: Plasma MDA levels were increased significantly in the Group G at 1 min before tourniquet release and 5 and 20 min after tourniquet release compared with before induction of general anaesthesia (baseline). Before intrathecal anaesthesia and before induction of general anaesthesia significantly decreased levels of MDA were observed both before and after tourniquet release compared to baseline. Plasma SOD and CAT concentrations were decreased significantly only at tourniquet release in the Group G compared with baseline. In the Groups S and T these enzymes were not changed significantly. Plasma GPx levels were not altered in any groups. CONCLUSION: Propofol administration may inhibit lipid peroxidation and restore antioxidant enzyme levels in extremity surgery requiring tourniquet application.     

丙泊酚对重症急性胰腺炎相关肺损伤保护作用的实验研究

目的：探讨丙泊酚对大鼠重症急性胰腺炎（SAP）相关肺损伤的保护作用及机制。方法45只雄性SD大鼠随机分为3组（n=15）：假手术组（S组）、重症胰腺炎组（SAP组）、丙泊酚组（P组）。以4％牛磺胆酸钠逆行胰胆管注射的方法制作SAP模型。丙泊酚组（P组）在制作SAP模型前30分钟经股静脉注射5mg·kg^-1,随后以10mg·kg^-1·h^-1。继续持续输注。各组均于造模12小时后取材,测定血清肿瘤坏死因子-a（TNF-ct）含量;采用RT-PCR法检测肺组织细胞间粘附分子-1（ICAM-1）mRNA的表达;同时检测肺组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性、湿干重比及对肺脏进行病理学评分。结果与SAP组相比,P组肺组织病理损伤程度、湿／干重比、肺组织MDA含量和SOD活性以及血清TNF—a和ICAM-1mRNA水平表达均显著降低（P〈0．05）。结论丙泊酚可减轻大鼠SAP相关肺损伤．其机制可能与其减少炎症因子的释放,减少中性粒细胞在肺内的积聚,抑制过氧化损伤有关。     

The Effects of Desferrioxamine and Quercetin on Liver Injury Induced by Hepatic Ischaemia-Reperfusion in Rats

Background: This study was designed to examine the effects of desferrioxamine and quercetin on hepatic ischaemia-reperfusion injury in rat.

Methodology: Thirty Wistar albino rats were randomized into five groups. Group I was the control group. Group II received no treatment. Group III and group IV received intramuscular injections of desferrioxamine (100 mg/kg per day) and quercetin (50 mg/kg per day) respectively. Group V was administered desferrioxamine and quercetin in combination. After treatment for 3 days, groups II, III, IV, and V were exposed to total hepatic ischaemia for 45 minutes. Plasma alanine aminotransferase levels, malondialdehyde and reduced glutathione activities were measured after reperfusion for 1 hour. Histopathological analysis of liver tissues was carried out.

Results: Our results indicated that tissue malondialdehyde levels and histopathological liver damage scores were significantly higher in the ischaemia-reperfusion group than in the control group. Administration of desferrioxamine, quercetin, and desferrioxamine+quercetin significantly decreased these parameters. Plasma alanine aminotransferase levels were also increased after ischaemia-reperfusion. Quercetin and desferrioxamine + quercetin significantly decreased the activity of this enzyme when compared to ischaemia-reperfusion group.

Conclusions: The present data suggest that both desferrioxamine and quercetin may be useful to protect against ischaemia-reperfusion induced liver damage.     

Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in venous ischemia-reperfusion injury: experimental study in rats

Flaps with venous occlusion have a decreased survival rate compared with arterial occlusion. It seems that several factors are involved in the etiology of total venous occlusion, including free radicals, edema, thrombosis, and reperfusion injury. In the present study, the authors evaluated the blockage of polymorphonuclear leukocyte endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent venous ischemia-reperfusion injury in rat epigastric island flaps. A skin flap (3 x 4 cm) supplied by the superficial epigastric artery and vein was harvested unilaterally in 40 male Wistar rats. Total venous occlusion of the skin flap was achieved. Arterial inflow was left intact. Rats were randomly divided into four groups (n = 10). In Group 1; rats were intravenously pretreated with 0.5 ml of 0.9 percent normal saline 15 min before applying a venous clamp, and the flaps were subjected to 6 hr of venous ischemia. In Group 2; rats were intravenously pretreated with 0.05 mg of monoclonal antibody to the intercellular adhesion molecule 1 (0.20 mg/kg) in 0.5 ml of 0.9 percent normal saline 15 min before applying the venous clamp, and the flaps were subjected to venous ischemia as in Group 1. In Group 3; rats were pretreated as in Group 1, and the flaps were subjected to 8 hr of venous ischemia. In Group 4; rats were pretreated as in Group 2, and the flaps were subjected to 8 hr of venous ischemia. The flaps were assessed histologically and by measuring viable and non-viable areas on postoperative day 7. Flap measurements revealed that blocking the action of ICAM-1 IN VIVO by administering monoclonal antibody significantly attenuated ischemic injury after 6 or 8 hr of venous occlusion.     

The effect of Shen-Fu on gastrointestinal tract injury and its potential mechanism during cardio-pulmonary bypass in patients undergoing cardiac surgery

Objective: To investigate the effect of Shen-Fu (SF) injection on gastrointestinal tract injury and its potential mechanism.Methods: Thirty-eight patients undergoing elective open heart surgery were assigned to Group C (control group, n = 18) and Group SF (n = 20) randomly. In Group SF, the patients received intravenous injection of SF (0.5 ml/kg) at the beginning of the surgery followed by a continuous infusion of 100 ml SF (1.0 ml/kg) solution diluted by saline at a rate of 0.004 ml · Kg-1 · min-1 with a Grasby pump. The control group was injected with normal saline in the same volume. Gastric intramucosal pH (pHi), activity of blood diamine oxidase ( DAO ), and concentrations of blood LPS and IL-6 were measured before CPB ( S0) and 1 h ( S1 ) and 2 h ( S2) after aortic declamping, respectively.Results: In Group C, pHi value was significantly lower at S1 and S2 than at S0 ( mean P <0.01) and blood DAO and concentrations of LPS and IL-6 were significantly higher at S1 and S2 than at S0 ( meanP < 0.01     

Treatment of posttraumatic syringomyelia

Object This paper presents results of a prospective study for patients undergoing surgery for posttraumatic syringomyelia between 1991 and 2010. Methods A group of 137 patients with posttraumatic syringomyelia were evaluated (mean age 45 ± 13 years, mean follow-up 51 ± 51 months) with pre- and postoperative MRI and clinical examinations presenting in this period and followed prospectively by outpatient visits and questionnaires. Surgery was recommended for symptomatic patients with a progressive course. Short-term results were determined within 3 months of surgery, whereas long-term outcomes in terms of clinical recurrences were studied with Kaplan-Meier statistics. Results Three groups were distinguished according to the type of trauma: Group A, patients with spinal trauma but without cord injury (ASIA E, n = 37); Group B, patients with an incomplete cord injury (ASIA C or D, n = 55); and Group C, patients with complete loss of motor function or a complete cord injury (ASIA A or B, n = 45). Overall, 61 patients with progressive symptoms underwent 71 operations. Of these operations, 61 consisted of arachnolysis, untethering, and duraplasty at the trauma level (that is, decompression), while 4 ASIA A patients underwent a cordectomy. The remaining procedures consisted of placement of a thecoperitoneal shunt, 2 opiate pump placements, and 2 anterior and 1 posterior cervical decompression and fusion. Seventy-six patients were not treated surgically due to lack of neurological progression or refusal of an operation. Neurological symptoms remained stable for 10 years in 84% of the patients for whom surgery was not recommended due to lack of neurological progression. In contrast, 60% of those who declined recommended surgery had neurological progression within 5 years. For patients presenting with neurological progression, outcome was better with decompression. Postoperatively, 61% demonstrated a reduction of syrinx size. Although neurological symptoms generally remained unchanged after surgery, 47% of affected patients reported a postoperative improvement of their pain syndrome. After 3 months, 51% considered their postoperative status improved and 41% considered it unchanged. In the long-term, favorable results were obtained for Groups A and C with rates for neurological deterioration of 6% and 14% after 5 years, respectively. In Group B, this rate was considerably higher at 39%, because arachnolysis and untethering to preserve residual cord function could not be fully achieved in all patients. Cordectomy led to neurological improvement and syrinx collapse in all 4 patients. Conclusions The technique of decompression with arachnolysis, untethering, and duraplasty at the level of the underlying trauma provides good long-term results for patients with progressive neurological symptoms following ASIA A, B and E injuries. Treatment of patients with posttraumatic syringomyelia after spinal cord injuries with preserved motor functions (ASIA C and D) remains a major challenge. Future studies will have to establish whether thecoperitoneal shunts would be a superior alternative for this subgroup.     

Neuronal and astroglial injuries in patients undergoing coronary artery bypass grafting and aortic arch replacement during hypothermic cardiopulmonary bypass

More than 50% of patients suffer neuropsychologic impairment after cardiac surgery. We measured neuron-specific enolase (NSE) and S-100 protein (S-100) in patients' serum as putative markers of neuronal and astroglial cell injury, respectively. Group I (n = 13) underwent coronary artery bypass grafting (CABG) with mild hypothermic cardiopulmonary bypass (CPB); Group II (n = 6) underwent aortic arch replacement with deep hypothermic CPB; Group III (n = 8) underwent CABG under normothermia without CPB. During and after the operation, serum levels of NSE and S-100 were significantly increased only in Groups I and II (during CPB), NSE still being increased 12 h after surgery in Group II. This suggests that neuronal and astroglial cell injuries are more likely in patients undergoing CABG with mild hypothermic CPB or aortic arch replacement with deep hypothermic CPB than in those undergoing CABG under normothermia without CPB. However, these increases of NSE and S-100 failed to reflect clinical brain damage. Rather, an electroencephalogram, was only capable of detecting neurologic complications after surgery. Implications: Neuronal and astroglial cell injuries are likely to occur during coronary artery bypass grafting with mild hypothermic cardiopulmonary bypass (CPB) or aortic arch replacement with deep hypothermic CPB. Conversely, patients undergoing coronary artery bypass grafting without CPB under normothermic conditions may be less likely to suffer brain cell injury.     

The ameliorating effect of melatonin on protamine sulfate induced bladder injury and its relationship to interstitial cystitis

PURPOSE: The pineal hormone melatonin was recently shown to have free radical scavenging ability and it reduces lipid peroxidation. In this morphological study we investigated the effects of melatonin on protamine sulfate (Sigma Chemical Co., St. Louis, Missouri) induced bladder injury. MATERIALS AND METHODS: Albino Wistar female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or protamine sulfate (bladder injury group) dissolved in phosphate buffered solution. In the protamine sulfate plus melatonin group after protamine sulfate instillation melatonin was injected intraperitoneally. Bladder morphology was investigated by light and electron microscopy. Tissue samples were also obtained to determine bladder malondialdehyde levels. RESULTS: In the bladder injury group ulcerated areas, an irregular glycosaminoglycan layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli, and dilated urothelial intercellular spaces were observed. In the bladder injury plus melatonin group a relatively normal urothelial topography, glycosaminoglycan layer and decreased number of mucosal mast cells, some dilatation between intercellular areas, less uniform microvilli and in most areas regular tight junctions were observed. CONCLUSIONS: Increased malondialdehyde levels as a result of protamine sulfate induction lead us to propose that free radicals may have a critical role in this injury. The significant decrease in malondialdehyde levels in the protamine sulfate plus melatonin group was in accordance with morphological findings. Thus, melatonin appears to exert a urothelial protective activity in a bladder injury model.