Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis

Tissue damage during surgery induces coagulation factors and activates platelets. Surgical pain may provoke release of catecholamines, leading to hypercoagulability. We have investigated the effect of surgical pain on blood coagulability and fibrinolysis in orthopaedic operations using tourniquets in 22 patients undergoing total knee replacement. Patients were allocated to one of two groups to receive extradural anaesthesia (EA; n = 11) or general anaesthesia (GA; n = 11). The EA group received lumbar extradural block with lidocaine. The GA group received only general anaesthesia, maintained with 1.5-2.5% sevoflurane and 66% nitrous oxide in oxygen. Using a thrombelastogram technique, blood coagulability and fibrinolysis were measured. Mean maximum amplitude (MA), which reflects coagulability, increased after tourniquet inflation (11%) in group GA whereas MA in group EA did not change. After tourniquet deflation, MA values in both GA and EA groups increased significantly (10% and 20%, respectively) (P < 0.05), and there was also a significant difference in MA between groups (P < 0.05). The fibrinolytic rate did not change in either group during tourniquet inflation, but increased significantly (160%) after tourniquet deflation. There was no significant difference in fibrinolytic rate between the groups. We conclude that the hypercoagulability seen in group GA could have been caused by surgical or tourniquet pain, or both, and that extradural anaesthesia is a useful technique to prevent hypercoagulability.      

血栓弹性图评价肾移植围术期的凝血状况

目的：采用血栓弹性图（TEG）评价肾移植围术期的凝血状况，并探讨术前血液透析对凝血功能的影响，方法：38例行肾移植术病人，按术前最后一次血液透析距手术的时间分为三组，A组（16例），小于6h，B组（12例）：6－24h,C组（10例），超过24h。三组均于术前，称植肾动静脉开放后10min及术毕采静脉血检测TEG（r,k,α角，MA及CI）。结果：A组术前TEG参数中r,k值均小于正常值，α角，MA及CI值均明显增高，B组术前TEG参数均在正常值范围内，C组术前r值的平均值为6.89min，超过了正常上限值，其MA平均值为57.21mm,低于正常下限值，与C组术前r值的平均值为6.89min，超过了正常上限值，其MA平均值为57.21mm，低于正常下限值；与C组相比，A组术前r值显著降低，α角，MA及CI值均升高（P＜0．05）。B,C两组动静脉开放10min后的TEG参数与术前值相比，均表现为r值缩短，MA与CI增加（P＜0．05），三组术毕TEG参数比较无显著差异（P＞0．05）。结论：TEG提示血透后的6h内血液呈高凝状态，24h后有纤溶的倾向。移植肾动静脉开放后血液亦呈高凝状态，有潜在的血栓形成的危险性。     

Lidocaine and bupivacaine exert differential effects on whole blood coagulation.

STUDY OBJECTIVES: To compare bupivacaine to lidocaine's effects on blood clotting at two concentrations, and to characterize and determine relative effects of two equianalgesic bupivacaine and lidocaine concentrations. DESIGN: Prospective, dual-controlled, whole blood equal volume admixture thrombelastographic (TEG) study. SETTING: University of Pennsylvania Medical Center operating rooms. PATIENTS: 20 ASA physical status I and II patients' blood comprised control groups and anesthetic groups. INTERVENTIONS: Analysis of whole blood clotting used six TEG channels for untreated and saline controls and four final concentrations (1.0% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, and 0.125% bupivacaine) of local anesthetics. Saline control and the local anesthetic-treated specimens underwent 8.3% hemodilution. MEASUREMENTS AND MAIN RESULTS: Blood was studied. Saline control or four anesthetic solutions (30 microliters) were added in random order two 5 TEG cuvettes. Whole blood (330 microliters) was mixed ex vivo at 37 degrees C. A sixth channel with untreated whole blood (360 microliters) acted as an undiluted control. Data for four TEG parameters [reaction time (r), angle (alpha), maximum amplitude (MA), and percent decrease in TEG amplitude from MA 30 minutes after MA acquisition (Lysis 30)] for undiluted control and saline volumetric controls were compared to each other using Student's t-test for paired observations. Lidocaine and bupivacaine groups' TEGs were compared to the paired saline control analysis of variance for repeated measures. A p-value less than 0.05 was considered significant. There was no difference between whole blood and saline control TEGs. All local anesthetics produced significant hypocoagulable changes from control. Angle alpha and MA were significantly decreased in all local anesthetic groups. Ther time was prolonged only in the high lidocaine-treated blood. Lysis was a feature of the low lidocaine and bupivacaine solutions. Equianalgesic lidocaine produced more profound hypocoagulable effects than did bupivacaine. CONCLUSIONS: Lidocaine and bupivacaine both significantly impaired TEG coagulation in a concentration-dependent manner. Lidocaine was significantly more hypocoagulable than bupivacaine at two similarly analgesic concentrations.     

Does hemodilution enhance coagulability?

Recent publications reported enhanced coagulability in hemodilution determined by TEG. In contrast, earlier reports have shown prolongation of in-vivo bleeding time in anemia. In order to take a closer look at this discrepancy undiluted and diluted anticoagulated blood samples (20 % with saline solution, hydroxyl-ethyl starch 6 % (HES), autologous platelet poor plasma (PPP)) were investigated by TEG (n = 10), ball (n = 10), and hook coagulometer (n = 15) as well as tests simulating primary hemostasis ex vivo (Platelet Function Analyzer PFA-100, n = 10). RESULTS: Dilution with plasma changed TEG parameters in a way, when started by recalcification of the blood sample, which is characteristic of enhanced coagulability (r decreased in all and k in 8 of 10 samples, maximal amplitude increased in 9 out of 10). With HES, changes in TEG parameters mainly indicated reduced coagulability (k increased in 7 out of 10, MA decreased in 10 out of 10). When the coagulation was additionally activated by PTT reagent (InTEG) the TEG parameters also mainly showed hypocoagulation with the three dilution solutions. Coagulation times with ball and hook coagulometers were significantly prolonged by dilution especially with saline (+ 25 % and + 17 %, p < 0.001). Dilution always significantly (often abnormally) prolonged closure time in PFA-100 (saline + 41 +/- 18 %, PPP + 37 +/- 20 %, HES + 69 +/- 24 %) demonstrating disturbance of primary hemostasis, particularly with HES. Conclusions: From the results obtained it can be concluded that the changes in the classical TEG (without addition of PTT-reagent), suggesting an enhanced coagulability, may be caused methodically as they are also found with autologous PPP. On the other hand, a disturbance of the primary hemostasis in hemodilution has to be taken into account from the results seen with the PFA-100 and a number of published data.     

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。     

异丙酚对β-淀粉样蛋白诱导大鼠皮层神经元损伤的影响

目的 探讨异丙酚对β-淀粉样蛋白(β-AP)诱导大鼠皮层神经元损伤的影响.方法 孕18 dSD大鼠,体外分离皮层神经元,5×104个/孔,每孔200μl接种于96孔培养板上,培养7 d.实验一:取15孔神经元随机分为5组(n=3):对照组;损伤组;异丙酚预防给药Ⅰ组加入β-AP 25μmol/L前24 h加入异丙酚50μmol/L,再孵育24h;异丙酚预防给药Ⅱ组同时加入异丙酚50 μmol/L和β-AP 25μmol/L,孵育24 h;异丙酚治疗给药组加入β-AP 25μmol/L后6 h,加入异丙酚50μmol/L,再孵育18 h.实验二:取18孔神经元随机分为6组(n=3):对照组;损伤组;脂肪乳剂组加入β-AP 25μmol/L后6 h,加入等容量10%脂肪乳剂,再孵育18 h;不同浓度异丙酚组加入β-AP 25μmol/L后6 h,分别加入异丙酚1、10、50 βmol/L,再孵育18 h.测定神经元乳酸脱氢酶(LDH)释放量和神经元活力.采用TUNEL法、Hoechst33342染色观察细胞凋亡情况,计算细胞凋亡率.结果 实验一:与损伤组比较,异丙酚预防给药组LDH释放量差异无统计学意义(P＞0.05),异丙酚治疗给药组神经元LDH释放量减少(P＜0.05).实验二:与损伤组比较,异丙酚50μmol/L组神经元LDH释放量减少,神经元活力升高,细胞凋亡率降低(P＜0.05).结论 异丙酚50 μmol/L治疗性给药可减轻β-淀粉样蛋白诱导大鼠皮层神经元损伤,预防性给药对其无影响.     

In vitro evidence of gender-related heparin resistance

Coagulability varies among men, women, and pregnant women, along a spectrum where the blood of men is the least and that of pregnant women the most coagulable. The effects of differences in coagulation status on the action of heparin cannot be measured by specific laboratory tests such as aPTT or anti-Factor Xa assay. Thromboelastography which measures whole blood coagulation can assess the effect of heparin against differing backgrounds of coagulation. The aim of this in vitro study was to explore differences in heparin effect between men, women and pregnant women. Fifteen male and female staff volunteers, and 15 pregnant women approaching term, donated venous blood, which was added to four cups in two TEG 5000 analysers. In the cups of the analysers was 0.03 mL of saline control, or heparin 0.4, 0.6 or 1 unit/mL. TEG variables r and k, angle and MA were compared across the groups using two way ANOVA. All subject groups demonstrated a significant heparin effect, which was least in the control group and greatest with 1 unit/mL (P < 0.0001). Across the subject groups, from men to pregnant women, increasing coagulability was seen, with shortening of r and k (P < 0.04), and increasing angle and MA (P < 0.0001). A relationship between gender and heparin was significant for r and k (P < 0.02) but not for angle and MA. This result assists the case against a one-size-fits-all approach to policies on heparinisation.     

瑞芬太尼和异丙酚对健康志愿者体外静脉血中性粒细胞呼吸爆发的影响

目的 评价瑞芬太尼和异丙酚对健康志愿者体外静脉血中性粒细胞(PMNs)呼吸爆发的影响.方法 健康志愿者12名,年龄20～40岁,体重55～65kg,取肘静脉血5 ml抗凝.采用正交实验设计确立实验因素为瑞芬太尼和异丙酚;实验水平数为5水平,即瑞芬太尼空白对照、溶媒(甘氨酸)对照、瑞芬太尼5、50、500 ng/ml和异丙酚空白对照、溶媒(脂肪乳)对照、异丙酚5、50、500μg/ml,用正交表L25(56),观察药物对静息状态和脂多糖(LPS)激活状态下PMNs呼吸爆发的影响,静息状态的PMNs不用LPS进行刺激,按实验设计方案加入相应药物孵育3 h;激活状态的PMNs根据用药时机分为预防性用药和治疗性用药,预防性用药加入相应药物孵育1 h,再加入LPS(终浓度1μg/ml)孵育2 h;治疗性用药首先加入LPS(终浓度1 μg/ml)孵育1 h,再加入相应药物孵育2 h.结果 瑞芬太尼50 ng/ml可增强静息状态下PMNs的呼吸爆发;各剂量瑞芬太尼治疗性用药均可增强LPS激活状态下PMNs的呼吸爆发(P＜0.05),预防性用药对PMNs的呼吸爆发无影响(P＞0.05).各剂量异丙酚及脂肪乳可降低静息和LPS激活状态下PMNs的呼吸爆发(P＜0.05),但各剂量异丙酚与脂肪乳比较差异无统计学意义(P＞0.05).瑞芬太尼和异丙酚对静息状态下和激活状态下PMNs呼吸爆发的影响没有交互作用.结论 瑞芬太尼对PMNs呼吸爆发的影响可能与PMNs所处的状态、用药剂量及用药时机有关;异丙酚的溶媒可抑制PMNs的呼吸爆发,而异丙酚本身无作用,且这种抑制作用与PMNs所处的状态及用药时机无关;瑞芬太尼和异丙酚对PMNs呼吸爆发的影响没有交互作用.     

Pro-coagulant effect of in vitro haemodilution is not inhibited by aspirin

We have conducted an in vitro coagulation study, using the thrombelastograph (TEG), to determine if the enhanced coagulability of whole blood after haemodilution with normal saline can still be demonstrated after administration of an antiplatelet agent. Aspirin inhibits the platelet-endothelial interaction that is part of the coagulation process. We investigated the role of aspirin in the phenomenon of haemodilution-induced coagulability to identify if the platelet-endothelial system is involved in the process. Previous work showed that the TEG is not altered by oral ingestion of aspirin. Blood from 20 volunteers was divided into two aliquots of 4 ml each. One sample was diluted by 20% by addition of 0.9% saline 1 ml while the other was not diluted and served as a control. Coagulation studies were performed using the TEG and enhanced coagulation was seen in the saline diluted samples. Subjects then received soluble aspirin 375 mg daily for 3 days, after which the tests were repeated. There was no difference in the control TEG values and saline enhancement of coagulation was preserved in all subjects after 3 days of aspirin administration. We conclude that aspirin had no effect on the observation that haemodilution with saline enhances the coagulability of whole blood.      

The usefulness of celiteactivated thromboelastography for evaluation of fibrinolysis

Purpose

Although thromboelastography is useful for measuring both coagulability and fibrinolysis, it takes about two hours to measure all parameters including fibrinolytic rate. The present study aimed to investigate the usefulness of celite-activated thromboelastography (TEGc)to evaluate fibrinolytic status in non-cardiac surgery.

Methods

Whole blood samples were obtained from 30 patients for non-cardiac surgery, and used for measurements of both native TEG (TEGn) and TEGc. The final concentration of 1% (w/v) celite was used for TEGc.

Results

Time for measurement of the fibrinolytic rate (FR) of TEGc in patients (56.7 ± 4.0 min) was less than half that of FR of TEGn (123.3 ± 15.6 min) (P < 0.05), suggesting a more rapid assessment of fibrinolytic status. A linear relationship was observed between FR values of TEGc and those of TEGn (r = 0.93,P < 0.0001), suggesting the usefulness of the fibrinolytic parameter of TEGc.

Conclusion

TEGc is a useful technique for a more rapid assessment of fibrinolytic status.     

Celite-activated thrombelastography in children

STUDY OBJECTIVE: To quantify global coagulation and establish normal ranges for the celite-activated thrombelastograph (TEG) in healthy pediatric patients. DESIGN: Prospective observational study. SETTING: Operating suite of a university-based hospital. PATIENTS: 110 healthy pediatric patients in four age groups and 25 healthy adult patients. INTERVENTIONS: Blood sampling for the celite-activated TEG was carried out after anesthetic induction. MEASUREMENTS: TEG indices: R time (reflecting time to fibrin formation), K time and alpha angle (fibrinogen-platelet interaction), maximum amplitude (reflecting maximal clot strength, platelet and fibrinogen function), TEG index (mathematical incorporation of the prior four measurements), and percent fibrinolysis at 30 minutes, were all recorded. MAIN RESULTS: Statistically significant differences between <12-month group in angle (compared to 25-48 month group) and % fibrinolysis (compared to all other pediatric groups). Significant differences in angle between two pediatric groups and adult group, and in the TEG index between three pediatric groups and adult group (all differences p < 0.05). CONCLUSIONS: These data identify changes of small magnitude in three celite-TEG parameters in healthy children compared to adults, without implication of abnormal coagulation between groups. Changes do not seem to be consistently related to age and will be useful for clinicians using the TEG to monitor (ab) normal coagulation in pediatric patients.     

Effect of propofol on sevoflurane agitation in children

BACKGROUND: Sevoflurane may be associated with a high incidence of agitation during recovery from anesthesia in children. We tested the hypothesis that bolus administration of propofol after sevoflurane anesthesia would reduce the incidence of recovery agitation compared with sevoflurane anesthesia alone. METHODS: We conducted a randomized, double-blinded study in 90 children, 1-7 yr of age, undergoing short general anesthesia. They were divided into three groups; 2 mg.kg-1 propofol (group P2), 1 mg.kg-1 propofol (group P1) and intralipid 0.2 ml.kg-1 as control (group C). After sevoflurane induction and maintenance and 5 minutes before the end of operation, propofol or intralipid was administered. We compared the speed and quality of each recovery. We made a new scoring system for the assessment of agitation. Each child received a point from -4 to 10 with this system. RESULTS: Recovery score was similar among the three groups (group P2 had point 4, group P1, point 5, and group C point 4). Recovery time in group P2 was significantly longer than that in group C (about 6 minutes). CONCLUSIONS: Bolus administration of propofol after sevoflurane anesthesia prolonged recovery time, but did not inhibit sevoflurane agitation compared with sevoflurane anesthesia alone.     

腹主动脉灌注丙泊酚减轻脊髓缺血-再灌注损伤与抗氧化和减轻钙超载的关系

目的 本研究拟探讨腹主动脉灌注丙泊酚减轻脊髓缺血-再灌注损伤是否与其抗氧化和减轻钙超载相关.方法 新西兰大耳白兔60只,随机均分为生理盐水(NS)组、10%脂肪乳(P0)组、丙泊酚30mg/kg(P30)组、40mg/kg(P40)组、50mg/kg(P50)组和60mg/kg(P60)组.全麻后开腹阻断肾动脉远端腹主动脉及双侧髂总动脉30min,并从阻断即刻开始,经股动脉预置导管向腹主动脉分别灌注生理盐水、10%脂肪乳及不同剂量的丙泊酚溶液至开放停止.再灌注48h,取L5脊髓节段,检测脊髓组织的超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和脊髓前角神经细胞内Ca2 荧光强度.结果 与NS和P0组比较,P30、P40、P50和P60组的SOD活性显著升高(P<0.05),MDA含量和Ca2 荧光强度显著降低(P<0.05).SOD活性:P50组最高(P<0.05),P40、P60组高于P30组(P<0.05).MDA含量:P50组最低(P<0.05),P60组低于P30、P40组(P<0.05).Ca2 荧光强度:P60组低于P50组,P50组低于P30、P40组(P<0.05).结论 丙泊酚可剂量依赖性地保护脊髓组织SOD活性、降低MDA含量和脊髓前角神经细胞内Ca2 荧光强度,提示该保护作用与其抗氧化和减轻神经细胞钙超载有关.     

Hydroxyethyl starch impairs in vitro coagulation

Background: Artificial colloids affect haemostasis. Particularly hydroxyethyl starch (HES) solutions may have detrimental effects on haemostatic mechanisms.
Methods: In a crossover study blood was withdrawn from ten volunteers. Ringer's acetate, 6% low molecular weight HES (M_w 120 000/molar substitution ratio 0.7), 10% low molecular weight HES M_w 200 000/0.5) and 6% high molecular weight HES (M_w 400 000/0.7) or 4% albumin was added to venous blood samples to make either 20 vol.% or 50 vol.% concentrations of each of the solutions. Samples were analyzed by thrombelastography (TEG).
Results: All HES solutions at 20 vol.% concentration impaired haemostasis as demonstrated by decreased clot formation rate (α-angle and maximum amplitude (MA)). In contrast, Ringer's acetate and albumin improved coagulability at 20 vol.% concentrations. Coagulation time (r+K) was prolonged at 50 vol.% dilutions of all solutions. The median r+K was greater with HES 400 ( P <0.05) and HES 200 (N. S.) than with HES 120.
Conclusion: We conclude that HES at 20 and 50 vol.% concentrations has an adverse effect on in vitro measures of coagulation. A 50% dilution with high molecular weight HES seems to impair coagulation more than low molecular weight HES. Ringer's acetate and albumin caused a hypercoagulable state at a concentration of 20 vol.%, but the higher concentration decreased coagulability.     

异丙酚对LPS诱导中性粒细胞Toll样受体2和Toll样受体4表达的影响

目的 探讨异丙酚对内毒素(LPS)诱导中性粒细胞Toll样受体2(TLR2)和TLR4表达的影响.方法 健康志愿者6名,年龄20～35岁,各采集外周静脉血样50 ml,加入20 U/ml肝素抗凝,分离提纯中性粒细胞,制备细胞悬液,然后随机分为6组,每组6皿:对照组(C组)不给予任何药物,置于37℃、5%CO_2培养箱中培养12 h;异丙酚脂质溶剂intralipid组(I组)、异丙酚组(P组)和LPS组(L组):分别加入intralipid(终浓度为5 μg/ml)、异丙酚(终浓度为5 μg/ml)或LPS(终浓度为1μg/ml),置于37℃、5%CO_2培养箱中孵育12 h;intralipid+LPS组(IL组)和异丙酚+LPS组(PL组)先分别加入intralipid(终浓度为5 μg/ml)或异丙酚(终浓度为5 μg/ml)后,置于37℃、5%CO_2培养箱中孵育20 min,然后加入LPS(终浓度为1μg/ml),置于37℃、5%CO_2培养箱孵育12 h.采用流式细胞仪测定中性粒细胞膜TLR2和TLR4的表达;采用荧光定量PGR检测中性粒细胞膜TLR2 mRNA和TLR4 mRNA的表达;采用ELISA法测定培养上清液TNF-α和IL-8的浓度.结果 与C组比较,I组和P组TLB2和TLR4的表达、1NF-α和IL-8L-8的浓度差异无统计学意义(P>0.05),L组和IL组TLR2和TLR4的表达上调,L组TNF-α和IL-8L-8的浓度升高,IL组IL-8浓度升高(P<0.05);与L组比较,IL组TLR2和TLR4的表达、TNF-α和IL-8L-8的浓度差异无统计学意义(P>0.05),PL组TLR2和TLR4的表达下调,TNF-α和IL-8L-8的浓度降低(P<0.05).各组TLR2 mRNA和TLR4 mRNA的表达差异无统计学意义(P>0.05).结论 异丙酚可下调LPS诱导的中性粒细胞TLR2和TLR4的表达,从而抑制炎性反应.     

Is platelet function as measured by Thrombelastograph monitoring in whole blood affected by platelet inhibitors?

Platelet inhibitors, especially the glycoprotein (GP) IIb/IIIa receptor antagonists, have demonstrated their effectiveness in reducing the acute ischemic complications of percutaneous coronary intervention (PCI) and in improving clinical outcomes in patients with acute coronary crisis. Three common platelet inhibitors observed in emergent cardiopulmonary bypass (CPB) for failed PCI are abciximab, eptifibatide, and tirofiban. An in vitro model was constructed in two parts to determine whether platelet aggregation inhibition induced by platelet inhibitors would be demonstrated by the Thrombelastograph (TEG) monitor when compared with baseline samples with no platelet inhibitor. In part A, 20 mL of fresh whole blood was divided into four groups: group I = baseline, group A = abcix-imab microg/mL, group E = eptifibatide ng/mL, and group T = tirofiban ng/mL. Platelet inhibitor concentrations in whole blood were derived starting with reported serum concentrations with escalation to achieve 80% platelet inhibition using the Medtronic hemoSTATUS and/or Lumi-aggregometer. A concentration range determined by our in vitro tests were chosen for each drug using concentrations achieving less than, equal to, or greater than 80% platelet inhibition. In part B, TEG analysis was then performed using baseline and concentrations for each drug derived in part A. Parameters measured were clot formation reaction time (R), coagulation time (K), maximum amplitude (MA) and alpha angle (A). Groups E1000 and E2000 extended R over control by 37% and 23%, respectively (p = 0.01 and 0.03). Groups E1000 and E2000 increased K times by 45% and 58% (p = .02 and .04). T160 samples prolonged K by 20% (p = 0.01). The angle or clot strength (A) was decreased in groups T160 and E1000 by 23% (+ 7.06 SD) and 18% (+ 11.23 SD), respectively (p = 0.001 and 0.01). The MA decrease was statistically significant in the T160, E1000 and E2000 by 9%, 6% and 13% respectively (p = 0.01). Samples treated with abciximab were comparable to control values for all parameters measured. Although statistical significance could be demonstrated with some parameters, sensitivity was only observed at increased doses and was not seen with all agents tested. In our in vitro model, the TEG monitor was unable to demonstrate clinically significant differences in platelet function and may not be reflective of platelet function in samples which have been treated with these GP IIb/IIIa inhibitors.     

Propofol attenuates diaphragmatic dysfunction induced by septic peritonitis in hamsters

BACKGROUND: Sepsis or peritonitis impairs diaphragmatic contractility and endurance capacity. Peroxynitrite, a powerful oxidant formed by superoxide and nitric oxide, has been implicated in the pathogenesis. Propofol scavenges this reactive molecule. The authors conducted the current study to evaluate whether propofol prevents diaphragmatic dysfunction induced by septic peritonitis. METHODS: Forty male Golden-Syrian hamsters (120-140 g) were randomly classified into five groups. Groups sham and sham-propofol 50 underwent sham laparotomy alone, whereas groups sepsis, sepsis-propofol 25, and sepsis-propofol 50 underwent cecal ligation with puncture. Groups sham and sepsis received infusion of intralipid, whereas groups sham-propofol 50, sepsis-propofol 25, and sepsis-propofol 50 received propofol at rates of 50, 25, and 50 mg.kg(-1).h(-1), respectively. Intralipid or propofol was subcutaneously infused from 3 h before surgery until 24 h after operation, when all hamsters were killed. Diaphragmatic contractility and fatigability were assessed in vitro using diaphragm muscle strips. Peroxynitrite formation in the diaphragm was assessed by nitrotyrosine immunostaining. Plasma nitrite-nitrate concentrations and diaphragmatic concentrations of malondialdehyde were determined. Using another set of animals, diaphragmatic inducible nitric oxide synthase activity was also measured. RESULTS: Twitch, tetanic tensions, and tensions during fatigue trials were reduced in group sepsis compared with group sham. In group SEPSIS, diaphragm malondialdehyde and inducible nitric oxide synthase activity, and plasma nitrite-nitrate concentrations increased, and positive immunostaining for nitrotyrosine residues was found. Propofol attenuated these changes. CONCLUSIONS: Pretreatment with propofol attenuated diaphragmatic dysfunction induced by septic peritonitis in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of propofol may be caused, in part, by inhibition of lipid peroxidation in the diaphragm caused by the powerful oxidant.     

Intermittent pneumatic foot compression can activate blood fibrinolysis without changes in blood coagulability and platelet activation

BACKGROUND: Intermittent pneumatic foot compression (IPC) is a useful technique for prophylaxis of peri-operative venous thromboembolism. The aim of this study was to determine the effect of IPC on blood coagulation/fibrinolysis and platelet function using a blood viscometer (Sonoclot) and a platelet aggregation monitor (WBA analyzer(TM)), respectively. Using the same blood samples, serum levels of tissue-type plasminogen activator (t-PA), thrombomodulin (TM) and activated protein C (APC) were also measured. METHODS: The soles and legs of each subject (n = 8) were compressed for 3 s (130 mmHg) at a 0.3-Hz interval using an IPC device. Parameters were measured 2 min before and at the end of 60-min compression. RESULTS: Parameters of the Sonoclot time-to-peak were shortened and clot retraction rate was increased significantly by IPC, whereas the other parameters did not change. These results indicate that IPC can activate blood fibrinolysis but not coagulability. A parameter of the WBA analyzer PATI (platelet aggregatory threshold index) did not change, indicating that IPC cannot activate platelet function per se. The concentration of t-PA decreased slightly but significantly. A decrease in the concentration of t-PA can lead to activation of fibrinolysis. Other humoral parameters did not change, indicating that IPC has no effect on endothelial function. Although neither blood coagulability nor platelet function were affected by IPC, fibrinolytic activity increased slightly, probably by activation of t-PA function. CONCLUSION: IPC is useful for prophylaxis for thromboembolism by activation of blood fibrinolysis as well as inhibition of blood stasis.     

Protective effects of propofol against ischemia/reperfusion injury in rat kidneys

Aim: The purpose of this study was to investigate and compare the efficiency of propofol in the reduction of injury induced by free radicals in a rat model of renal ischemia/reperfusion (I/R). Method: Twenty-four Wistar rats were divided into four groups in our study. Rats in the sham group underwent laparotomy and were made to wait for 120 min without ischemia. Rats in the control group were given nothing with ischemia–reperfusion. Rats in the I/R groups were given propofol (25 mg/kg) and 10% intralipid (250 mg/kg) ip, respectively, 15 min before the ischemia for 60 min followed by reperfusion for 60 min. The kidney tissues of the rats were taken under anesthesia at the end of the reperfusion period. Evaluation of biochemical malondialdehyde (MDA), superoxide dismutase, and catalase activities and histopathological analysis were performed with these samples. Results: I/R significantly increased MDA levels (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the propofol group compared to control group (p < 0.05). In the propofol group, the level of histopathological scores is significantly decreased than control and intralipid groups in ischemia–reperfusion. Conclusion: Our results demonstrate that I/R injury was significantly reduced in the presence of propofol. The protective effects of propofol may be due to their antioxidant properties. These results may indicate that propofol anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

In vivo investigation into the effects of haemodilution with hydroxyethyl starch (200/0.5) and normal saline on coagulation

We have investigated the effects of haemodilution with either saline or hydroxyethyl starch (200/0.5) (HES) on blood coagulation in healthy volunteers in vivo. Standard haematological tests (packed cell volume (PCV), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin III, bleeding time and platelet aggregation), and thrombelastography (TEG) were performed before and after administration of either 0.9% saline 1000 ml or HES 1000 ml i.v. over a 30-min period. Dilution of PCV and platelet concentrations as a result of volume load were 9% in the saline group and 19% in the HES group. Reductions in fibrinogen (18.6% and 28.8%) and antithrombin III (25.5% and 37.8%) were significantly greater than could be explained by haemodilution alone in both groups. Indices of platelet aggregation were significantly enhanced by saline haemodilution, but not by HES, which inhibited epinephrine-induced aggregation and prolonged bleeding time. TEG in the saline group showed significantly shortened r and k times (24% and 26%, respectively), and increased alpha angle (24%) and maximum amplitude (MA, 6%). HES haemodilution decreased MA (11%) but did not affect other TEG variables. We conclude that haemodilution of normal blood exerted a procoagulant effect, possibly by enhancement of thrombin formation. Circulating concentrations of antithrombin III were depleted more than could be explained by haemodilution alone, leading to a hypercoagulable state. This effect was offset by an antiplatelet action of HES, which was not seen with saline. The mechanism is unknown.