Xanthine oxidoreductase and preservation injury in human liver transplantation

BACKGROUND: Preservation injury is a major cause of primary graft dysfunction in liver transplantation (LT). Oxidative damage is considered to be the first event leading to graft damage. Xanthine oxidoreductase (XOR) and neutrophil activation, two sources of reactive oxygen species, could play a role in the development of graft dysfunction. METHODS: We determined activities of XOR forms, polymorphonuclear elastase (PMN-E), aminotransferases, and hyaluronic acid in plasma of 20 patients undergoing LT. Samples were taken from the radial artery (RA) before the anhepatic phase; from the portal vein (PV) before reperfusion; from graft caval effluent (CE) at reperfusion; and from RA, PV, and the hepatic vein (HV) 10 and 90 min postreperfusion. RESULTS: The graft, but not recipient bowel, released XOR into blood (XOR in CE, median, 61.2 mU/g protein [range, 1.9-160.4 vs. undetectable in PV before reperfusion). Circulating XOR was transformed from dehydrogenase to reversible oxidase (XOrev) (XOrev-to-XOR ratio, 48.1% in CE and 65.1% in HV 90 min postreperfusion). Neutrophil activation was detected in the recipients before reperfusion, and in liver at early post-reperfusion (median PMN-E was 0.85 microg/g protein [range, 0.01-1.58] in RA before the anhepatic phase; 2.22 microg/g protein [range, 0.20-5.88] in PV prereperfu-sion; and 3.60 microg/g protein [range, 0.48-6.78] in HV 10 min postreperfusion). XOR, but none of the other markers, was higher in the CE of patients with moderate primary graft dysfunction than in those with slight primary graft dysfunction. CONCLUSIONS: XOR release and neutrophil activation are produced during LT, and they are potentially injurious mechanisms associated with this therapy.     

Influence of cold ischemia time on complement activation, neopterin, and cytokine release in liver transplantation

OBJECTIVES: The aim of this study was to determine whether a cold ischemia time (CIT) of >12 hours influences the activation of complement as well as the plasma concentrations of neopterin, interleukin (IL)-6, or IL-8 in orthotopic liver transplantation (OLT). PATIENTS AND METHODS: Eighteen consecutive patients undergoing OLT using a veno-venous bypass technique were divided into 2 groups: duration of CIT >12 hours (group 1; n = 11), and CIT <12 hours (group 2; n = 7). Blood samples were drawn preoperatively, 1 minute before, and 120 minutes after reperfusion. RESULTS: Preoperatively, complement split products, neopterin, IL-6, and IL-8 levels did not differ between the groups. At 120 minutes after reperfusion, the concentrations of C3a, SC5b-9, neopterin, IL-6, and IL-8 were significantly increased in both groups compared with the preoperative values or the levels determined 1 minute before reperfusion (P < .05). Patients in group 1 showed significantly higher IL-8 levels at 120 minutes after reperfusion (P < .05). CONCLUSION: Complement is activated and pro-inflammatory cytokines released after reperfusion in OLT using a veno-venous bypass technique, but only IL-8 plasma levels were influenced by the duration of CIT. Therefore, alterations following prolonged CIT seem to not be complement-mediated.     

Effects of methylprednisolone on complement activation and leukocyte counts during cardiopulmonary bypass

Generation of the complement activation products C3dg and terminal complement complex (TCC) and numerical changes in peripheral granulocytes (PMN) and lymphocytes were assessed in patients undergoing aortocoronary bypass surgery with extracorporeal circulation (ECC). Fluid from bronchial lavage performed preoperatively and 4 hours postoperatively was analyzed for granulocyte elastase activity and PMN content. Ten of the 20 patients received methylprednisolone (30 mg/kg b.w.) immediately before ECC. No difference was found between them and the control group regarding C3dg and TCC, and both groups showed similar postoperative decrease of peripheral blood lymphocytes. The postoperative PMN count in peripheral blood was significantly higher in the methylprednisolone group than in the controls from 12 hours onwards. In bronchial lavage fluid the postoperative PMN count was unaltered in the methylprednisolone group, but significantly increased in the controls. No granulocyte elastase activity was found before or after surgery in either group. The results indicated that methylprednisolone does not affect complement activation during cardiopulmonary bypass, but increases the granulocytes in peripheral blood postoperatively.     

肝移植术病人围术期中性粒细胞Toll样受体2表达与术后SIRS的关系

Objectlve investigate the role of Toll-like receptor 2 (TLR2) on polymorphonuclear neutrophil (PMN) during perioperative period in the development of postoperative systemic inflammatory response syndrome (SIRS) in patients undergoing orthotopic liver transplantation (OLT).Methods Twenty patients (18 male and 2 female, aged 33-58 yr and weighing 52-73 kg) with ASA Ⅲ or Ⅳ (NYHA Ⅱ or Ⅲ )undergoing OLT were studied. Blood samples were collected from the central vein for determination of TLR2 expression on PMN and plasma TNF-α, IL-1β and IL-8 concentrations before induction of anesthesia (T1, baseline), at 25 min of anhepatic phase (T2), 3 h (T3) and 24 h after beginning of reperfusion of the allograft (T4). The expression of TLR2 was measured by flow cytometry and the serum concentrations of TNF-α, IL-1β and IL-8 were measured by enzyme linked immunosorbant assay (ELISA). The patients were divided into SIRS and non-SIRS group depending on whether the patients developed SIRS or not within 7 days after operation. The diagnosis of SIRS was based on the criteria laid down by ACCP and SCCM in 1992.Results Ten patients developed SIRS within 7 days after operation. There was no significant difference in Child-Turcotte-Pugh (CTP) scores between the two groups. Compared with non-SIRS group, the TLR2 expression on PMN and the serum IL-1β concentration were significantly increased at T4 and the serum IL-8 concentration was significantly increased at T3 in SIRS group.There was positive correlation between serum TNF-α concentration and TLR2 expression on PMN in SIRS group ( r= 0.607, P ＜0.05).Conclusion The expression of TLR2 on PMN increases significantly at 24 h after beginning of reperfusion of allograft and may play an important role in the development of postoperative SIRS.     

肝移植术病人围术期中性粒细胞Toll样受体2表达与术后SIRS的关系

目的 研究肝移植术病人围术期中性粒细胞Toll样受体2(TLR2)表达与术后全身炎性反应综合征(SIRS)的关系.方法 择期行肝移植术的终末期肝病病人20例,年龄33～58岁,体重52～73 kg,心功能Ⅱ或Ⅲ级,ASAⅢ或Ⅳ级.于麻醉诱导前(T1)、无肝期25 min(T2)、新肝期3 h(T3)、新肝期24 h(T4)时,中心静脉采血样,采用流式细胞仪测定中性粒细胞TLR2表达;ELISA法测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-8(IL-8)浓度;按术后7 d内是否发生SIRS,分为SIRS组与非SIRS组.2组TNF-α、IL-1β和IL-8浓度和TLR2表达进行Spearman相关分析.结果 术后7 d内有10例病人发生SIRS.与T1时比较,SIRS组T4时中性粒细胞TLR2表达上调,T2-4时TNF-α浓度升高,T3,4时IL-1β浓度升高,T3时IL-8浓度升高(P＜0.05或0.01);与NSIRS组比较,SIRS组T4时中性粒细胞表达上调,血清IL-1β浓度升高,T3时血清IL-8浓度升高(P＜0.05或0.01).SIRS组TNF-α浓度与中性粒细胞TLR2表达呈正相关(r=0.607,P＜0.05).结论 肝移植术后病人发生SIRS可能与新肝期24 h中性粒细胞TLR2表达上调有关.     

Granulocytes in bronchial lavage fluid after major vascular surgery

Increased numbers of polymorphonuclear granulocytes (PMN) in the airways, as measured by PMN content in bronchial lavage fluid (P less than 0.01), were found 3 h postoperatively in ten patients undergoing surgery for lumbar aortic aneurysms. An increase in plasma levels of the complement split product C3dg from 6 (0-19) AU/ml preoperatively to 20 (13-50) AU/ml 3 h after surgery (P less than 0.01), indicates an activation of the complement cascade. These changes were not accompanied by increased elastase activity in the bronchial lavage fluid or by major changes in pulmonary blood gas exchange or vascular resistance, indicating that massive PMN activation, analogous to that proposed in adult respiratory distress syndrome (ARDS) had not taken place. In conclusion, complement system activation and migration of PMN into the airways, as seen in connection with major vascular surgery, does not seem to contribute to ARDS-type pulmonary dysfunction.     

Activation of intracellular neutrophil elastase in the transplantation of ischemic liver.

Ischemia-reperfusion injury is an important cause of primary nonfunction of transplanted organs, and neutrophil elastase has been implicated in the pathophysiology of ischemia-reperfusion injury. We assessed the kinetics of intracellular neutrophil elastase (INE) activity in canine liver transplantation. Mongrel dogs underwent orthotopic whole-liver transplantation. The animals in group I (n = 6) received fresh liver grafts, and all of the dogs survived longer than 24 h. The animals in group II (n = 5) received liver grafts injured by 30 min of warm ischemia. Only 1 animal survived longer than 24 h after reperfusion. A significant increase in the serum ALT and LDH levels was observed in group II after reperfusion of the graft. Isolated peripheral neutrophils were homogenized, and the neutrophil elastase activity in the supernatant was determined by using a spectrophotometric assay. The INE activity was expressed as the neutrophil elastase value per 1 x 10(10) peripheral neutrophils. In group I, the INE activity 10 min and 2 h after reperfusion was 7.6 +/- 2.6 and 6.1 +/- 2.4 U, respectively. In group II, this activity was 25.9 +/- 7.4 and 44.3 +/- 23.7 U, respectively. There was a significant correlation between serum LDH levels and INE activity 10 min after reperfusion (gamma = 0.70, p < 0.02). In conclusion, the INE activity increased more sharply after the reperfusion of ischemically injured liver grafts. The INE activity correlates with serum LDH levels immediately after reperfusion, suggesting that the increase in the INE activity depends on the severity of ischemic damage.     

19例原位肝移植术中凝血弹性图变化及与ACT相关性的临床研究

目的 探讨国人原位肝移植术中凝血弹性图（TEG）的变化及其与激活全血凝块形成时间（ACT）的相关性。方法 19例病人分为急性肝衰组（8例）与肝肿瘤组（11例）,接受原位肝移植术,无肝期采用体外静脉－静脉转流。两组病人分别于术前、无肝前（手术开始后120min,I 120)、无肝的30min（Ⅱ 30）、新肝前5min（Ⅲ－5）、新肝后5min（Ⅲ＋5）、30min（Ⅲ＋30）、60min（Ⅲ＋60）、120min（Ⅲ＋120）,8个时间点,分别观察硅燥土激活的全血TEG及ACT的变化。19例病人中有6例于新肝后5min同时观察肝素酶修正后的TEG与非肝素酶修正后的TEG及ACT的变化。结果 肝衰组TEG值（r、r k、αlpha角或α、MA）的变化主要在Ⅱ＋30min、Ⅲ－5min、Ⅲ＋5min,肝肿瘤组TEG值（r、r k、αMA）的变化均在新肝后5min、30min、60min。与术前值相比,两组TEG值的表现为r与r k延长,α与MA减小（P＜0．05、0．01）。相关研究表明,两组r k与ACT均呈正相关（r分别为0．743及0．634,P＜0．01）。其中6例于新肝后5min,有肝素酶与无肝毒酶的全血TEG值差异亦显著（P＜0．01）,后者经静注鱼精蛋白50－75mg后,两组TEG值差异无统计学意义（P＞0．05）。结论 TEG提示原位肝移植术中的凝血紊乱主要发生在无肝期及新肝早期,TEG指标r k与ACT有相关性。肝素酶修正后的全血TEG可提示新肝期体内存在肝素化效应,需用鱼精蛋白拮抗。     

Two-stage liver transplantation: an effective procedure in urgent conditions

Montalti R, Busani S, Masetti M, Girardis M, Di Benedetto F, Begliomini B, Rompianesi G, Rinaldi L, Ballarin R, Pasetto A, Gerunda GE. Two-stage liver transplantation: an effective procedure in urgent conditions.
Clin Transplant 2010: 24: 122–126. © 2009 John Wiley & Sons A/S.
Abstract:  Temporary portocaval shunt and total hepatectomy is a technique used in the presence of toxic liver syndrome because of fulminant hepatic failure, hepatic trauma, primary non-function (PNF), and eclampsia. We performed this technique on four patients. An indication for anhepatic state was severe hemodynamic instability in three of them. Etiologies of these three patients were as follows: PNF after liver transplantation, ischemic hepatitis after right hepatic artery embolization, and massive reperfusion syndrome during a liver transplantation. In the fourth patient, during the liver transplantation when hepatic artery was ligated, a kidney carcinoma in the donor graft was discovered. We decided to complete the hepatectomy and to construct a temporary portocaval shunt.
Mean anhepatic phases were 19 h and 15 min. All patients survived the two-stage liver transplantation procedure without major complications. Our cases demonstrated that temporary portocaval shunt while awaiting urgent liver transplantation could be an effective "bridge" in selected patients who develop toxic liver syndrome; however, a short time between portocaval shunt and transplantation and careful intensive care managements are mandatory.     

Goal directed preemptive ephedrine attenuates the reperfusion syndrome during adult living donor liver transplantation

BackgroundEnd-stage liver disease is associated with marked hemodynamic disturbances that are further deteriorated during liver transplantation and is aggressively represented in the form of postreperfusion syndrome (PRS).AimThe aim was to test the hypothesis that preemptive ephedrine administration pre-reperfusion targeting a rational level of mean arterial blood pressure (MAP) of 85–100 mmHg, may reduce the incidence of PRS.Patient and methodsOne hundred recipients for adult living donor liver transplantation (ALDLT) were prospectively randomized into 2 groups; group C, control group and group E, who received ephedrine 2.5–5 mg/min starting 5 min before reperfusion till mean arterial blood pressure (MAP) reached 85–100 mmHg. Hemodynamic parameters including MAP, heart rate (HR), Transesophageal Doppler (TED) parameters including corrected flow time (FTc), systemic vascular resistance (SVR), and cardiac output (COP) were measured; just predrug administration, just before reperfusion, just after reperfusion, 5 min after reperfusion and at the end of surgery. Cold and warm ischemia times (C/WIT), duration of anhepatic phase and total duration of surgery were recorded. The incidence of PRS, the need of rescue vasoconstrictor for hemodynamic instability at time of reperfusion, need for postreperfusion vasoconstrictor infusions, over shooting of hemodynamics, postreperfusion fibrinolysis indicated by fibrinogen level and maximum lysis parameter of rotational thromboelastometry (ROTEM) were compared between both groups.ResultsThe mean dose of ephedrine required was (12.5 ± 7.5 mg). Group E had statistically significant increase in MAP, SVR, and COP; just before reperfusion, just after reperfusion and 5 min after reperfusion readings. There were no statistical significant differences between the 2 groups at the end of surgery. The incidence of PRS and the need of rescue adrenaline at the time of reperfusion, and the postreperfusion need for vasoconstrictor infusion decreased significantly in group E when compared to group C. Also postoperative mechanical ventilation decreased significantly in group E.ConclusionThe preemptive goal directed titration of ephedrine against a target MAP pre-reperfusion could decrease the incidence of PRS by 40%, attenuated the hypotensive response to reperfusion and decreased the need for postreperfusion vasoconstrictor support without over shooting of any of the monitored hemodynamic indices.     

Glucose metabolism during liver transplantation in dogs

Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation performed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 +/- 12 mg/dl (mean +/- SEM) after laparotomy and 183 +/- 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 +/- 9 and 88 +/- 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P less than 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 +/- 17 and 240 +/- 24 mg/dl, 5 and 30 min after reperfusion, respectively (P less than 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 +/- 37 and 346 +/- 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P less than 0.05). Arterial plasma insulin, measured in five animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 +/- 14.2 to 108.4 +/- 38.1 pg/ml (P less than 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver.     

The minimal flush volume for washout of preservation fluid in liver transplantation

OBJECTIVES: Organ preservation is one of the important steps that predicts the patient outcome. However, after revascularization, the high concentration of potassium that influxes into the circulation might cause immediate postreperfusion hyperkalemia. To prevent this complication, the portal vein has been washed out with flush fluid to remove preservation fluid before reperfusion. Up to now, it has not been established what exact amount volume of albumin provides washout of the UW solution. METHODS: Eleven of 20 patients who underwent orthotopic liver transplantation (OLT) between December, 2003, and June, 2005, were enrolled in this study. OLT was performed following the standard technique. Five percent albumin (1000 mL) was flushed through the portal vein canula before reperfusion of the donor liver. Every 100 mL of flush fluid effluent was collected from an incomplete infrahepatic inferior vena cava anastomosis for electrolyte measurement. The 10 flushed fluid samples were measured for potassium concentration. Mean arterial pressure was monitored preoperatively, at 1-minute intervals after reperfusion and at 60 minutes after reperfusion. RESULTS: We observed that 61.5% of potassium was removed after only 100 mL of flush fluid, and 90.8% after 500 mL. Only one patient in this study had an effluent potassium reduction that did not achieved 90% after 500- or 1000-mL flush. However, this patient did not develop either postreperfusion syndrome or hyperkalemia. One patient did experience postreperfusion hyperkalemia (6.20 mEq) with severe hypothermia and cardiac arrest. Five patients had stable hemodynamic profiles and five patients, transient, reversible hypotension without postreperfusion hyperkalemia. DISCUSSION AND CONCLUSIONS: We propose that the minimal flush volume for washout of preservation fluid in liver transplantation is 500 mL, to reduce the risk of postreperfusion syndrome and hyperkalemia.     

A possible increase in plasma norepinephrine by removal of the liver

Background: It has recently been suggested that the human liver plays an important role in clearing plasma norepinephrine, especially in restricting most of the norepinephrine to reach the systemic circulation from the gut.
Methods: We examined the changes in plasma catecholamine levels in a patient undergoing extracorporeal hepatic resection and 4 patients undergoing living-related orthotopic liver transplantation.
Results: While the changes in plasma epinephrine levels were not necessarily consistent with the proposal that plasma catecholamine levels increase during the anhepatic period, plasma norepinephrine did show a transient increase in accordance with the anhepatic period in all cases. Although we could not rule out the increase in the inflow rate of norepinephrine into plasma, the interrupted hepatic elimination of norepinephrine, especially released from the gut, seemed to be partly responsible for the anhepatic period-associated increase in plasma norepinephrine.
Conclusion: The present finding might have the potential to improve perioperative management of patients undergoing extracorporeal hepatic resection and orthotopic liver transplantation.     

Extrahepatic Metabolism of Sevoflurane in Children Undergoing Orthotopic Liver Transplantation

Background: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation.

Methods: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode.

Results: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 [mu]M (sevoflurane group) versus 1.4 +/- 0.5 [mu]M (isoflurane group) P < 0.05).     

Serum Vasopressin Concentrations During Orthotopic Liver Transplantation

Background

We report measurements of the temporal response of serum vasopressin concentrations in the period after reperfusion of the liver graft during orthotopic liver transplantation (OLT).

Methods

Vasopressin concentrations were determined in 11 adult patients undergoing OLT by radioimmunoassay of samples collected after induction, at 5 minutes prior to reperfusion, and at 10, 20, 30, 40, 50, 60, 90, and 120 minutes after reperfusion.

Results

Pre-incision vasopressin concentrations ranged from <0.5 to 2.6 pg/mL (reference serum vasopressin, <1.7 pg/mL). Overall, levels increased before reperfusion, but fell thereafter. Individual patients manifested elevated levels during the period after reperfusion. Values immediately before reperfusion exhibited most variability, ranging from 0.8 to 40 pg/mL (median, 15; interquartile range [IQR], 4-29) Median vasopressin concentrations 10 minutes postreperfusion were 7.6 pg/mL (IQR, 3-27). Only 3 of the 11 patients failed to generate vasopressin levels >20 pg/mL. In each of these patients, hemodynamics were satisfactory without the need for additional pressor infusion. Maximum vasopressin concentration measured in any patient was 85 pg/mL. There was no correlation between vasopressin concentration and mean blood pressure or systemic vascular resistance index.

Conclusion

Vasopressin concentrations during OLT vary widely and are elevated periodically during the anhepatic and postreperfusion stages, with no apparent relationship between vasopressin concentrations and blood pressure. Although vasopressin concentrations were not as high as those measured during some other clinical situations, these data suggest that a relative vasopressin deficiency is not a direct cause of hypotension during OLT.     

Extrahepatic metabolism of sevoflurane in children undergoing orthotopic liver transplantation

BACKGROUND: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation. METHODS: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode. RESULTS: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 microM (sevoflurane group) versus 1.4 +/- 0.5 microM (isoflurane group) P < 0.05). CONCLUSIONS: These results demonstrate the existence of an extrahepatic metabolism of sevoflurane at least in children with end-stage liver disease.     

肝移植术中血栓弹力图和常规凝血监测指标相关性研究

目的 观察肝移植术中血栓弹力图(TEG)和常规凝血监测指标的相关性.方法 行肝移植手术的患者40例,分别于麻醉诱导后(T1)、无肝期10 min(T2)、新肝期后15 min(T3)、关腹前30 min(T4)四个时点测定静脉血Plt、凝血酶原时间(PT)、国际标准化比值(INR)、凝血酶时间(TT)、激活部分凝血酶时间(APTT)、纤维蛋白原(FIB)及动脉血TEG指标:反应时间(R)、血块形成时间(K)、角度(α)、最大振幅(MA).结果 R与PT、INR、APTT成正相关(r分别为0.891、0.931、0.702,P<0.05或P<0.01),与FIB成负相关(r为-0.706,P<0.05).α与PT、INR、APTT成负相关(r分别为-0.864、-0.844、-0.678,P<0.05或P<0.01).MA与FIB、Plt成正相关(r分别为0.779、0.817,P<0.01),与PT、INR、APTT成负相关(r分别为-0.843、-0.829、-0.704,P<0.05或P<0.01).结论 肝移植术中TEG指标和常规凝血监测指标存在明显相关性.     

Reduced need for vasopressors in patients receiving aprotinin during orthotopic liver transplantation

BACKGROUND: Graft reperfusion in orthotopic liver transplantation is often associated with significant hemodynamic changes, including decreased systemic vascular resistance and arterial blood pressure. Vasopressive drugs are often required to maintain adequate perfusion pressure during the early postreperfusion period. The exact mechanism of this postreperfusion syndrome is unknown, but release of bradykinin, a potent vasodilatator, via the kallikrein system may play a role. Aprotinin is a broad-spectrum inhibitor of serine proteases such as kallikrein and therefore may ameliorate the postreperfusion syndrome and reduce the need for vasopressors. METHODS: In a randomized, double-blind study, the authors compared hemodynamic variables (systemic vascular resistance, cardiac index, arterial blood pressure, mean pulmonary artery pressure, central venous pressure) and the requirement of epinephrine during transplantation in 67 patients who received either high-dose aprotinin (2 x 10(6) kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 x 10(6) KIU/h, 1 x 10(6) KIU before reperfusion; n = 24), regular-dose aprotinin (2 x 10(6) KIU at induction, continuous infusion of 0.5 x 10(6) KIU/h; n = 21), or placebo (n = 22). RESULTS: Baseline characteristics were similar for all three groups. Erythrocyte transfusion requirement was significantly higher in the placebo group compared with both aprotinin-treated groups. No major differences in hemodynamic variables were found between the three groups. The total amount of epinephrine (median, range) used during transplantation, however, was significantly lower in patients who received aprotinin (high dose, 20, 0-170 microg; regular dose, 30, 0-140 microg), compared with patients who received placebo (70, 0-2,970 microg; P = 0.0017). This difference was largely attributable to differences in the early postreperfusion period. CONCLUSIONS: Prophylactic use of aprotinin ameliorates the postreperfusion syndrome in orthotopic liver transplantation, as reflected by a significant reduction in vasopressor requirements.     

New inflammation markers for early detection of spondylodiscitis

Summary Even today a significant feature of spondylodiscitis is the long interval between the onset of symptoms and the establishment of the diagnosis (on average 6.4 months in our study). In order to improve early detection of spinalinfections, new markers of inflammation were determined in patients with spondylodiscitis. Neopterin is produced by macrophages after their activation by T-lymphocytes, polymorphonuclear neutrophil (PMN) elastase is set free by activated granulocytes. Erythrocyte sediment rate (ESR) showed the highest sensitivity of all determined inflammation markers, but reached only a poor diagnostic specificity. The sensitivity of the white blood cell count was poor. C-reactive protein (CRP) and neopterin reached a sensitivity of 75% each in spondylodiscitis and had a good diagnostic specifity. Sensitivity of PMN elastase reached 67%. Contrary to ESR the new inflammation markers were also helpful in the following up of treated spondylodiscitis. PMN elastase showed quickest normalization of all inflammation parameters. For early detection of spondylodiscitis and clinical follow up we recommed combined determinations of CRP, neopterin and PMN elastase.     

Neutrophil elastase and oxygen radicals enhance monocyte chemoattractant protein- expression after ischemia/reperfusion in rat liver

BACKGROUND: The monocyte chemoattractant protein-1 (MCP-1) is produced during reperfusion injury and induces tissue factor that is the initiator of the clotting cascade. Neutrophil elastase is a crucial mediator of inflammatory tissue damage. Activation of the coagulation system stimulates cytokine production by activated leukocytes. We investigated the effects of neutrophil elastase and oxygen radicals generated by hypoxia associated with microthrombus formation on MCP-1 expression after ischemia/reperfusion in rat liver. METHODS: In vitro MCP-1 production by macrophages after stimulation with human neutrophil elastase (HNE) or oxygen radicals generated by hypoxanthine and xanthine oxidase was examined. Liver ischemia was induced in rats by occluding the portal vein for 30 min. An inhibitor of human neutrophil elastase (ONO-5046*Na, 10 mg/kg) and antithrombin III (AT-III, 250 U/kg) were injected i.v. 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. RESULTS: Human neutrophil elastase or oxygen radicals significantly enhanced in vitro MCP-1 production by macrophage. Serum MCP-1 concentrations reached a peak at 6 hr after reperfusion and then gradually decreased. However, pretreatment of animals with AT-III or ONO-5046*Na alone resulted in significantly smaller increases in serum concentrations of MCP-1 after reperfusion. Pretreatment with both ONO-5046*Na and AT-III produced additive effects. The combined treatment with ONO-5046*Na and AT-III significantly reduced MCP-1 mRNA in liver after ischemia/reperfusion. CONCLUSIONS: MCP-1 production by macrophages is stimulated by neutrophil elastase and oxygen radicals generated by hypoxia, probably due to microthrombus formation after ischemia/reperfusion of the rat liver.