不同抗栓药物组合对先天性心脏病介入封堵术后P-选择素及纤维蛋白原的影响

目的:研究不同抗栓药物组合对先天性心脏病介入封堵术后P-选择素(Ps)和纤维蛋白原(Fg)的影响。方法:51例室间隔缺损(VSD)和房间隔缺损(ASD)行介入封堵术的患者,随机分为3组:①阿司匹林组(A组);②阿司匹林加氯吡格雷组(B组);③阿司匹林加氯吡格雷加低分子肝素组(C组)。所有患者分别采用ELISA和凝固法测定术前及术后24 h、48 h的血浆Ps和Fg水平,并分别于术后24 h、1个月、3个月、6个月随访复查心脏B超、心脏事件和出血倾向。结果:3组术前、术后24 h Ps比较均差异无统计学意义(P>0.05)。Ps术后48 h较同组术前、术后24 h明显降低(P<0.05),C组较A、B组降低明显(P<0.05),A、B组之间差异无统计学意义(P>0.05);3组术前的Fg差异无统计学意义(P>0.05),术后24 h较同组术前均升高(P<0.05),术后48 h较同组术后24 h明显降低(P<0.01),但仍高于术前(P<0.05)。C组术后24 h和48 h Fg的升高幅度明显低于A、B组(P<0.05),而A、B组之间则差异无统计学意义(P>0.05)。术后随访超声心动图无心内血栓形成及心脏事件发生。结论:阿司匹林加一般剂量的氯吡格雷在短期抑制血小板活性方面并未显示其叠加作用,3药联用能更好的抑制血小板活性及Fg的形成。     

双侧胸椎旁神经阻滞复合全麻对心内直视手术患者应激反应的影响

目的:探讨双侧胸椎旁神经阻滞复合全麻对心内直视手术患者应激反应影响。方法: 择期二尖瓣置换术患者40例,随机分为两组:双侧胸椎旁神经阻滞复合全麻组（P组）和单纯全麻组（G组）,每组20例。P组患者麻醉诱导前经T3、4间隙行双侧胸椎旁间隙穿刺置管,两侧分别注射试验剂量3.75 g/L罗哌卡因5 ml,5 min后分别给予首次量3.75 g/L罗哌卡因15 ml。于麻醉前、体外循环(CPB)前、术毕及术后24 h抽取静脉血,测定血浆胰岛素、皮质醇及血管紧张素Ⅱ（AngⅡ）浓度。记录两组心脏复跳情况、术后正性肌力药使用率、机械通气时间、ICU滞留时间、肺部并发症发生率、心衰发生率及死亡率。结果: 与麻醉前比较,两组患者胰岛素、皮质醇及AngⅡ水平均从CPB前开始升高,至术毕达到高峰(P<0.05或P<0.01),P组患者术后24 h降至正常水平。与G组比较,胰岛素水平在术后24 h两组差异无统计学意义,术毕及术后24 h皮质醇及AngⅡ水平均低于G组(P<0.05),术毕胰岛素水平低于G组（P<0.05）。P组患者术后24 h多巴胺使用量、机械通气时间明显低于G组(P<0.05)。结论: 双侧胸椎旁神经阻滞可一定程度上抑制心内直视手术患者应激激素释放。     

Age-related augmentation of stroke tendency evaluated using plasma P-selectin levels

Plasma soluble P-selectin is thought to be a useful marker for thrombotic diseases. To evaluate the thrombotic state and risk of stroke in aged healthy subjects, we investigated plasma P-selectin levels in healthy subjects and ischemic stroke patients. Plasma P-selectin was measured in 67 healthy subjects and 35 aged (>or= 65 years of age) patients with chronic ischemic stroke using a sandwich enzyme-linked immunosorbent assay (ELISA). Plasma P-selectin was significantly higher in aged (>or= 65 years of age) healthy subjects than in young (< 65 years of age) healthy subjects. Significant difference did not exist between aged healthy subjects and aged stroke patients who were not receiving anti-platelet agents. Anti-platelet agent had no significant effect on plasma P-selectin levels in aged stroke patients. The amounts of P-selectin released from platelets into the plasma after stimulation with adenosin diphosphate in young and aged healthy subjects were not significantly different. Elevated levels of P-selectin in aged healthy subjects suggests the existence of a subclinical thrombotic state which can result in a stroke. Elevated P-selectin levels are not thought to be due to platelet hyperfunction.     

EFFECT OF EPIDURAL ANALGESIA ON THE GLYCOREGULATORY ENDOCRINE RESPONSE TO SURGERY

Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anaesthesia. In addition to general anaesthesia five of the patients had continuous epidural analgesia effective for the first 26 postoperative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but no changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anaesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin.     

Increased soluble P‐selectin levels following deep venous thrombosis: cause or effect?

Deep vein thrombosis (DVT) is associated with coagulation abnormalities, but evidence of excess platelet activity is scant. Soluble P-selectin is a marker of platelet activity, with high levels being found in patients with thrombotic disease. We measured soluble P-selectin by enzyme-linked immunosorbent assay (ELISA) in plasma from 89 patients with objectively confirmed DVT and in 126 healthy age- and sex-matched control subjects, and found higher levels in the patients (P = 0.011). Taking the risk of DVT with a level of soluble P-selectin < 238 ng/ml to be 1, the relative risk of DVT with a soluble P-selectin level >238 ng/ml was 2.1 (95% CI 1. 2-3.6). These high levels may be a reflection of a generalized hypercoagulable state that, with factors such as the presence of persistent thrombin generation, could be responsible for excess platelet activation.     

Postprandial hypertriglyceridemia associated with inflammatory response and procoagulant state after a high-fat meal in hypertensive patients

OBJECTIVE: To investigate the changes of inflammatory factors and hemostatic variable in plasma after a high-fat meal in normocholesterolemic patients with essential hypertension. METHODS: A total of 60 hypertensive patients were randomly assigned to accept a single high-fat meal (group 1, n=40) or not (group 2, n=20) in the morning after an overnight fast, and 20 healthy participants (group 3) consumed a single high-fat meal on the same day. Plasma lipid profiles, high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), soluble P-selectin and plasminogen activator inhibitor type 1 (PAI-1) antigen levels were measured at fasting and 4 h after meal ingestion. RESULTS: Postprandial triglyceride levels increased significantly in groups 1 and 3 (P<0.01), whereas levels were higher in group 1 (P<0.001). Postprandial plasma TNFalpha, hsCRP, soluble P-selectin and PAI-1 antigen levels increased in group 1 (P<0.001) but not in group 3. Postprandial plasma triglyceride level was correlated with log(hsCRP) (P<0.001), TNFalpha (P<0.001), soluble P-selectin (P<0.01) and PAI-1 antigen (P<0.05) levels, respectively. Both postprandial plasma level of soluble P-selectin and that of PAI-1 antigen were positively and significantly correlated with those of log(hsCRP) (P<0.01) and TNFalpha (P<0.001), respectively. CONCLUSION: Postprandial hypertriglyceridemia in hypertensive patients is associated with inflammatory response and procoagulant state.     

Soluble endothelial adhesion molecules during paediatric cardiovascular surgery with or without cardiopulmonary bypass

BACKGROUND: Paediatric cardiovascular surgery with or without cardiopulmonary bypass induces a complex pattern of pro- and anti-inflammatory responses. It is suspected that they may contribute to changes on the vascular endothelium. The endothelial response to cardiosurgical trauma and cardiopulmonary bypass, especially in children, has yet to be well established. PATIENTS AND METHODS: We studied 29 children undergoing cardiovascular surgery with cardiopulmonary bypass, comparing them with 21 not undergoing bypass. The groups did not differ significantly with respect to age, sex, weight and preoperative parameters. Blood samples were drawn 24 h before surgery, after onset of anaesthesia, after onset of cardiopulmonary bypass and after rewarming in those undergoing bypass, or immediately after surgery in the control group, 4 h and 2 days after surgery, at discharge, and months after surgery during out-patient follow-up. Serum levels of soluble E-selectin, P-selectin and P-selectin glycoprotein ligand-1 were measured by enzyme-linked immunoassay. RESULTS: Paediatric cardiovascular surgery leads perioperatively to the significant decreases of the serum levels of soluble P- and E-selectin, as well as of soluble P-selectin glycoprotein ligand-1 (all p < 0.05). The time course, and all concentrations, of these molecules were not significantly different with and without bypass. The decreases, however, were more pronounced with cardiopulmonary bypass. Preoperative baseline values were reached months after surgery. CONCLUSION: Endothelial activation of release of adhesion molecules is reduced during paediatric cardiovascular surgery. Endothelial activity is more perturbed with cardiopulmonary bypass and for a long time after surgery.     

Plasma P-selectin is increased in thrombotic consumptive platelet disorders

P-selectin is a 140-kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells that on cell activation is expressed on the cell surface and also secreted into the plasma. The secreted form of P-selectin, like plasma P-selectin, differed from platelet membrane P-selectin in that its molecular mass was approximately 3 kD lower under reducing conditions. Both the secreted and plasma forms of P-selectin contained cytoplasmic sequence as determined by Western blot analysis with an affinity-purified rabbit anti-P-selectin cytoplasmic peptide antibody. We have measured plasma P- selectin and beta-thromboglobulin (beta TG) concurrently in (1) patients with consumptive thrombotic disorders, including disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura (TTP)/haemolytic uremic syndrome (HUS); (2) patients with idiopathic thrombocytopenic purpura (ITP); and (3) healthy controls. Patients with DIC, HIT, and TTP/HUS, but not ITP, had significantly elevated plasma P-selectin and beta TG levels when compared with their age-matched healthy controls. The increased plasma P-selectin and beta TG in patients with thrombotic disorders were likely to be the result of in vivo platelet and endothelial cell damage or activation. We also found that avoidance of veno-occlusion and other tedious measures customarily taken during blood collection and sample preparation to prevent in vitro platelet activation did not affect plasma P-selectin assay results. In addition, plasma P-selectin levels were not influenced by the presence of renal failure or heparin administration. These results indicate that plasma P- selectin may be a useful new marker for thrombotic diseases.     

Increased plasma levels of soluble P-selectin in rheumatic mitral stenosis

BACKGROUND: Previous studies have demonstrated that platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS). However, in patients with MS, the plasma level of soluble P-selectin (a marker of platelet activation) remains unsettled. METHODS AND RESULTS: A total of 20 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty (PTMV) were studied (group 1; 16 patients in permanent atrial fibrillation, and 4 patients in sinus rhythm). The plasma levels of soluble P-selectin in the femoral vein and artery, and right and left atria before PTMV and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase, sandwich, enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble P-selectin in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in permanent lone atrial fibrillation [group 3]). The plasma levels of soluble P-selectin were significantly elevated in group 1 patients (49.78 +/- 37.72 ng/mL) [mean +/- SD] compared with group 2 (25.52 +/- 15.38 ng/mL) and group 3 patients (32.17 +/- 14.18 ng/mL) [p < 0.005]. In group 1 patients, the plasma levels of soluble P-selectin in the left atrium did not significantly differ from those in the right atrium, femoral vein, or femoral artery (p = 0.05). The area of mitral valve increased significantly after PTMV (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2), p < 0.0001). The mean left atrial pressure fell significantly and immediately after PTMV (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg, p < 0.0001). The peripheral venous plasma levels of soluble P-selectin obtained before PTMV did not significantly fall after PTMV (before, 49.8 +/- 37.7 ng/mL; 10 min after, 39.8 +/- 19.1 ng/mL; 1 week after, 46.1 +/- 20.8 ng/mL; and 4 weeks after, 41.2 +/- 15.9 ng/mL; p = 0.145). CONCLUSIONS: The venous plasma levels of soluble P-selectin in patients with moderate-to-severe MS were significantly higher than those in healthy volunteers or patients with lone atrial fibrillation. In addition, in patients with MS, there was no difference in the plasma levels of soluble P-selectin between the left and right atrial blood and between peripheral and atrial blood. Moreover, there was no change in soluble P-selectin levels as a result of PTMV.     

全麻联合胸椎旁神经阻滞对肺手术患者麻醉效果的影响

目的:探讨全麻联合胸椎旁神经阻滞对肺手术患者麻醉效果的影响。方法:86例择期开胸行肺手术患者随机分为全麻联合胸椎旁神经阻滞组(E组)及单纯全麻组(F组),观察2组患者术中的血流动力学,芬太尼及异氟烷的用量及术后镇痛效果。结果:E组患者与F组相比,E组患者的术中血流动力学更趋平稳,术中芬太尼及异氟烷用量少,术后清醒时间早及镇痛效果更好(P<0.01)。结论:对肺部手术患者采取全麻联合胸椎旁神经阻滞比单纯用全麻的麻醉效果好。     

Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function.

BACKGROUND: Atrial fibrillation is associated with increased risk of stroke and thromboembolism, possibly by conferring a prothrombotic or hypercoagulable state. However, it is unclear whether or not this differs in the clinical subgroups of chronic atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. We therefore hypothesized that: (i) there are differences in the prothrombotic state between these patients; and (ii) reduction in indices of hypercoagulability would follow elective electrical cardioversion of persistent atrial fibrillation and the return of left atrial function. PATIENTS AND METHODS: We studied 69 patients with chronic atrial fibrillation: 23 with paroxysmal atrial fibrillation (16 males; mean age 65 years+/-SD 13); 23 with persistent atrial fibrillation (16 males; 65 years+/-13), with a mean duration of atrial fibrillation of 3 months (range 2 to 6 months); and 23 with permanent atrial fibrillation (16 males; 67 years+/-10). Blood results were compared to 20 age- and sex-matched healthy controls. The patients with persistent atrial fibrillation then underwent elective DC cardioversion, with Doppler echocardiographic examinations and bloods tests performed prior to cardioversion, and at 3 and 12 weeks afterwards. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P-selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). RESULTS: Permanent atrial fibrillation was associated with significantly raised levels of von Willebrand factor, soluble P-selectin and fibrinogen (all P<0.001); paroxysmal atrial fibrillation with significantly elevated levels of plasma von Willebrand factor (P=0.0067) and fibrinogen (P=0.0001) but not soluble P-selectin (P=0.472); and persistent atrial fibrillation with normal levels of fibrinogen, von Willebrand factor and soluble P-selectin when compared to healthy controls (all P=ns). Stepwise multiple regression analyses demonstrated that the presence of atrial fibrillation was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P-selectin levels. Electrical cardioversion of the patients with persistent atrial fibrillation did not significantly alter levels of von Willebrand factor (P=0.766), soluble P-selectin (P=0.726) or fibrinogen (P=0.50) despite maintenance of sinus rhythm and a significant return of left atrial systolic function (as quantified by the presence of A wave on Doppler echocardiography) at 3 months. CONCLUSION: There were significant differences in the prothrombotic state when patients with paroxysmal and permanent atrial fibrillation are compared to matched patients with persistent atrial fibrillation or controls in sinus rhythm. Cardioversion of persistent atrial fibrillation did not significantly alter indices of hypercoagulability even after 3 months maintenance of sinus rhythm, despite the return of atrial systole.     

Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor.

Abnormal platelet activation and an increased risk of thrombosis are frequent findings in cancer. As soluble adhesion molecule P-selectin is being increasingly recognized as reflecting increased platelet activation, we hypothesized raised levels in patients with cancer, obtaining plasma from 24 patients with a cross-section of haematological cancers, 41 with breast cancer, and from an equal number of healthy controls for each patient group. Levels of soluble P-selectin were compared with those of von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity, fibrinolysis and coagulation, respectively). We found raised soluble P-selectin, fibrinogen and vWf in both patient groups compared with their controls (P < 0.01). vWf and soluble P-selectin were higher in the haematological cancers than in breast cancer patients (by 30 and 74%, respectively; both P < 0.01). There was no significant difference in levels of PAI-1 between any group. There were no differences in soluble P-selectin or vWf when the data from the women with breast cancer were classified according to tumour size, lymph node involvement or presence of vascular invasion. We conclude that the platelet marker soluble P-selectin is raised in both haematological and breast cancer, and is higher in the former, but is unrelated to the type or stage of breast cancer.     

Soluble P-selectin is present in normal circulation and its plasma level is elevated in patients with thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome

Summary. P-selectin is an integral membrane glycoprotein stored in the secretory granules of platelets and endothelial cells. To determine whether soluble P-selectin may be present in the circulation of healthy humans, we used a sandwich immunoassay to assess citrated plasma from 50 subjects. P-selectin was present in concentrations ranging from 19 to 521 ng/ml (mean ± SD = 121 ± 84 ng/ml). The apparent molecular weight of P-selectin immunoisolated from platelet-poor plasma was similar to that of the detergent-soluble form isolated from platelet membrane. Plasma levels of P-selectin were unaffected by the following procedures: (1) drawing of blood in the presence of protease inhibitors; (2) stimulation of platelet-rich plasma with aggregating agents; (3) ultracentrifugation at 100000 g for 120 min at 4°C or filtration through a 0·22 μm membrane; or (4) preincubation of platelet-poor plasma with immobilized anti-platelet glycoprotein Ib monoclonal antibodies. It appeared that plasma P-selectin did not result from the in vitro activation of platelets, nor was it derived from platelet microparticles. We also found that plasma P-selectin levels were significantly elevated in patients with thrombotic thrombocytopenic purpura (12 patients, 332 ± 184 ng/ml, P<0.001) and haemolytic uraemic syndrome (17 patients, 297 ± 191 ng/ml, P < 0.0001), as compared to the normal levels. Thus, these data should facilitate the study of the pathophysiological significance of circulating P-selectin.     

急性冠状动脉综合征患者P-选择素水平与冠状动脉病变的关系

目的探讨急性冠状动脉综合征(ACS)患者可溶性P-选择素(sP-选择素)水平及其与冠状动脉病变的关系。方法应用酶联免疫吸附法检测54例ACS患者(ACS组)、15例稳定性心绞痛患者(SA组)和19例冠状动脉造影正常者(对照组)血浆sP-选择素水平,对冠状动脉粥样硬化病变程度按照病变支数、Gensini评分和美国心脏病学会和美国心脏病协会A、B、C型分型进行评估。结果ACS组sP-选择素水平高于SA组和对照组(P<0.01);sP-选择素水平与冠状动脉病变数量,Gensini评分,A、B、C型冠状动脉病变程度均为正相关。结论ACS患者P-选择素水平明显升高,提示P-选择素是ACS临床识别和预测的炎症指标;P-选择素水平受冠状动脉粥样硬化程度的影响。     

Alterations of hemostasis after laparoscopic and open surgery

Background: After tissue injury caused by trauma or surgery, alterations of hemostasis are observed and there is a risk for postoperative thromboembolic complications. Laparoscopic surgery, by causing limited tissue injury, appears to be associated with a lower risk for thromboembolism than open surgery. We conducted a prospective randomized study in order to detect potentially existing differences in activation of coagulation and fibrinolytic pathways between open and laparoscopic surgery.

Methods: Forty patients suffering from chronic cholelithiasis were randomly assigned to undergo open (group A n = 20) or laparoscopic cholecystectomy (group B n = 20) by the same surgical and anesthesiology team. Demographic data were comparable. Blood samples were taken (a) preoperatively, (b) at the end of the procedure, (c) 24 h postoperatively and (d) 72 h postoperatively. The following parameters were measured and compared within each group and between groups: platelets (PLT), soluble fibrin monomer complexes (SFMC), fibrin degradation products (FDP), D-dimers (D-D), fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT). Thrombin–antithrombin III complexes (TAT) were measured at 24 and 72 h postoperatively. Prothrombin fragment 1 + 2 (F1 + 2) was measured at 24 and 72 h postoperatively in 11 patients of group A and 13 patients of group B, respectively.

Results: Demographics were comparable between groups. Immediately postoperatively, TAT and F1 + 2 were significantly higher in group A as compared to group B (p < 0.05). They also increased significantly postoperatively as compared to preoperative levels within each group (p < 0.05).

D-dimers were significantly higher in group A as compared to group B (p < 0.01) immediately postoperatively. D-dimers also increased significantly postoperatively in group B as compared to preoperative levels (p < 0.001).

FIB decreased slightly in both groups at 24 h postoperatively but there was a significant increase in group A as compared to group B (p < 0.01).

SFMC were detected twice in group A and only once group B.

FDP levels over 5 μg/ml were detected more often in group A than in group B (p < 0.05). No patient from either group suffered thromboembolism or abnormal bleeding as a postoperative complication.

Conclusions: Open surgery as compared to laparoscopic procedures leads to activation of the clotting system of a higher degree. Although of a lower degree, hypercoagulability is still observed in patients undergoing laparoscopic surgery and, therefore, routine thromboembolic prophylaxis should be considered.     

早期调脂干预对急性心肌梗死患者炎症因子的影响

目的观察早期较大剂量阿托伐他汀治疗急性心肌梗死(AMI)3d后患者血清可溶性CD40L(sCD40L)、P-选择素及可溶性血管粘附分子水平的变化,以探讨早期调脂干预对AMI斑块稳定、抑制炎症反应的作用。方法选取43例AMI患者随机分为常规治疗组(无服用任何调脂药物,21例)和阿托伐他汀组(立普妥20mg,qd,22例),测定治疗前后sCD40L、P-选择素、可溶性细胞间粘附分子-1(sICAM-1)和可溶性血管细胞间粘附分子-1(sV-CAM-1)的水平。结果两组治疗前后血脂水平变化无显著性差异。阿托伐他汀组治疗后血清sCD40L、P-选择素、sICAM-1分别下降35％、41％、30％,明显低于治疗前水平(P<0.05),sVCAM-1稍下降,但无统计学意义;在常规治疗组治疗前后上述指标均无明显变化。在阿托伐他汀组sCD40L、P-选择素、sICAM-1的降低与总胆固醇(TC)(分别为r=0.08,P=0.56;r=0.16,P=0.34;r=0.12,P=0.41),低密度脂蛋白胆固醇(LDL-C)(分别为r=0.09,P=0.88;r=0.11,P=0.46;r=0.18,P=0.77)的下降百分数之间无相关关系。结论在AMI的早期使用阿托伐他汀治疗3d,可明显降低血清炎症因子水平,可能有利于动脉粥样硬化斑块的稳定。     

Acute hyperglycemia increases soluble P-selectin in male patients with mild diabetes mellitus.

The aim of this study was to examine if acute hyperglycemia (an oral glucose tolerance test) activates platelet function, endothelial cells or thrombin generation in diabetic patients and healthy controls. Eleven males with mild type II diabetes mellitus and 11 healthy male volunteers, matched for age and body mass index, were investigated before and after the glucose load. Soluble P-selectin, von Willebrand factor antigen and markers of thrombin generation in plasma were determined by immunoassays, and platelet P-selectin expression (unstimulated and agonist-stimulated) by flow cytometry in whole blood. Acute hyperglycemia elevated plasma soluble P-selectin from 32.5 to 50.9 ng/ml in the diabetic group (P = 0.05) but not in the controls (from 27.3 to 28.8 ng/ml; P = 0.6). Also, soluble P-selectin levels were higher in patients with diabetes than in healthy controls during hyperglycemia, but not in the fasting state. Adenosine diphosphate- and thrombin-induced platelet P-selectin expression was slightly, but significantly, decreased by the glucose load, whereas platelet P-selectin expression in unstimulated samples was not affected. Plasma levels of von Willebrand factor and thrombin generation were similar in patients and controls, and were not altered by hyperglycemia. In conclusion, we found that acute hyperglycemia elevates soluble P-selectin in plasma in males with mild type II diabetes mellitus. Our observation of unaltered plasma levels of the endothelial marker von Willebrand factor is in agreement with platelets being the main source of P-selectin released into plasma following hyperglycemia. Thus, platelets in individuals with type II diabetes may be more susceptible to hyperglycemia than platelets in non-diabetic individuals.     

Hormonal responses to graded surgical stress

We tested the hypothesis that selected hormonal responses to surgery reflect the degree of surgical stress. Plasma norepinephrine, epinephrine, thromboxane B2, cortisol, serum angiotensin converting enzyme, thyroxine, triiodothyronine, free thyroxine, and free triiodothyronine levels were measured preoperatively, and then one hour, 24 hours, and five days postoperatively in three groups of patients. The groups were as follows: group 1, "minimal" stress, eg, inguinal hernia repair (n = 10); group 2, "moderate" stress, eg, cholecystectomy (n = 12); and group 3, "severe" stress, eg, subtotal colectomy (n = 9). Patients in group 1 showed no significant surgery-induced changes in hormonal values. The stress-induced changes in patients in groups 2 and 3 were seen at one and occasionally 24 hours; however, by five days postoperatively, circulating hormone values had returned to preoperative levels. Increases in plasma cortisol, norepinephrine, and epinephrine, and decreases in serum angiotensin converting enzyme levels characterized the surgery-induced hormonal changes. Conclusions are as follows: hormonal responses do reflect the degree of surgical stress; the hormonal changes are transient, lasting no longer than 24 hours in patients after uncomplicated surgery; hormonal responses to minimal surgical stress are negligible.     

Decreased plasma soluble P-selectin level in coronary sinus after successful coronary angioplasty in patients with unstable angina]

P-selectin, an adhesion molecule, is involved in the alpha-granules of platelets with several factors such as platelet factor 4 (PF-4) and in Weibel-Parade bodies of endothelial cells with von Willebrand factor. The levels of the soluble form of P-selectin increase after angina episodes in patients with unstable angina, indicating that soluble P-selectin is associated with platelet activation and thrombogenesis in the coronary circulation. To evaluate the effect of successful coronary angioplasty on platelet activation or thrombogenesis in the coronary circulation, plasma soluble P-selectin, PF-4 and von Willebrand factor antigen levels were measured in blood obtained from the coronary sinus before and after successful coronary angioplasty in 15 patients with unstable angina. Fifteen patients with normal coronary angiograms served as controls. Plasma P-selectin, PF-4 and von Willebrand factor antigen levels were determined by sandwich enzyme-linked immunosorbent assays. Increased plasma soluble P-selectin (159.7 +/- 74.5 vs 78.7 +/- 26.4 ng/ml, p < 0.01) and PF-4 (456.5 +/- 87.0 vs 118.7 +/- 62.3 IU/ml, p < 0.01) levels were found in patients with unstable angina compared with those in controls, and were significantly decreased after angioplasty (147.8 +/- 69.6 ng/ml, p < 0.05; 401.6 +/- 108.5 IU/ml, p < 0.05), whereas von Willebrand factor antigen was unchanged. The ratio of plasma soluble P-selectin levels after and before angioplasty correlated with the corresponding ratio of plasma PF-4 levels (r = 0.53, p < 0.05), but not with the ratio of plasma von Willebrand factor antigen levels. The plasma levels of soluble P-selectin, which increase in the coronary circulation in patients with unstable angina, decrease after successful coronary angioplasty. Such data indicate that soluble P-selectin is associated with platelet activation and the therapeutical procedure improves the thrombogenic state in the coronary circulation.     

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.