Low serum S100beta protein levels following coronary artery surgery with or without cardiopulmonary bypass

BACKGROUND: S100beta protein has been used as a serum marker of brain injury during cardiac surgery. Previous studies may have been confounded by the re-transfusion of shed mediastinal blood, which has a high concentration of S100beta. AIM: To examine serum S100beta levels in coronary artery surgery patients in whom re-transfusion of shed mediastinal blood was avoided, and to compare levels with and without cardiopulmonary bypass (CPB). METHODS: Serum S100beta levels were measured preoperatively, pre-heparin, post-protamine and 24 h postoperatively in 31 patients undergoing elective coronary artery surgery with (n = 14) or without (n = 17) CPB. The postoperative values were compared to their preoperative controls using two-tailed paired t-tests. RESULTS: There was a minor increase in serum S100beta post-protamine in the CPB group only (0.41 ng/mL; P < 0.01). All other levels in both groups were within normal limits. CONCLUSIONS: Coronary artery surgery without CPB is not associated with an increase in serum S100beta. The observed increase in the CPB group was four- to ninefold lower than levels previously reported. A possible explanation for the lower level was the avoidance of retransfusing shed mediastinal blood. If elevated S100beta levels are thought to represent a cerebral insult caused by CPB, the magnitude of the insult might be less than previously assumed.     

中心静脉压在体外循环心脏术后急性肾损伤中的作用

目的:观察中心静脉压(CVP)对体外循环心脏手术后急性肾功能损伤(AKI)的影响。方法:前瞻性观察2013年7月1日至2014年5月30日期间,在安贞医院行体外循环心脏手术的患者。根据患者手术结束时的CVP是否10mm Hg(1mm Hg=0.133k Pa)来分为高CVP组或低CVP组。收集手术类型、术前射血分数、术前血清肌酐水平、术后血清肌酐水平、术中体外循环时间、术后重症监护病房(ICU)停留时间、术后机械通气时间等围术期临床资料。患者出院后所有患者均进行电话随访。采用Cox回归模型分析预后相关影响因素。结果:共有1 941例患者纳入本研究,患者平均年龄为(51.97±13.62)岁。CVP组801例(41.3%),低CVP组1 140例。高CVP组347例(43.3%)患者发生AKI,低CVP组86例患者发生AKI,差异有统计学意义(P0.0001)。高CVP组每一期AKI的发病率均高于低CVP组。多因素分析显示,CVP与AKI相关(OR=1.416(1.346~1.489),P0.0001),而MAP与CO和AKI无相关性。高CVP组患者30天死亡30例(3.8%),低CVP组死亡6例(0.5%),两组病死率差异有统计学意义(P0.0001)。多因素回归分析发现CVP使患者病死率增加(HR:1.196,每增加1mm Hg,95%CI:1.114~1.285,P0.0001)。结论:CVP增高与体外循环心脏术后发生AKI有关,是患者死亡的独立危险因素。     

Low serum S100β protein levels following coronary artery surgery with or without cardiopulmonary bypass

Background: S100β protein has been used as a serum marker of brain injury during cardiac surgery. Previous studies may have been confounded by the re-transfusion of shed mediastinal blood, which has a high concentration of S100β.Aim: To examine serum S100β levels in coronary artery surgery patients in whom re-transfusion of shed mediastinal blood was avoided, and to compare levels with and without cardiopulmonary bypass (CPB).Methods: Serum S100β levels were measured preoperatively, pre-heparin, post-protamine and 24 h postoperatively in 31 patients undergoing elective coronary artery surgery with (n = 14) or without (n = 17) CPB. The postoperative values were compared to their preoperative controls using two-tailed paired t-tests.Results: There was a minor increase in serum S100β post-protamine in the CPB group only (0.41 ng/mL; P < 0.01). All other levels in both groups were within normal limits.Conclusions: Coronary artery surgery without CPB is not associated with an increase in serum S100β. The observed increase in the CPB group was four- to ninefold lower than levels previously reported. A possible explanation for the lower level was the avoidance of retransfusing shed mediastinal blood. If elevated S100β levels are thought to represent a cerebral insult caused by CPB, the magnitude of the insult might be less than previously assumed.     

婴幼儿CPB期间血浆S100蛋白、NSE水平变化及参附注射液的干预作用

目的探讨婴幼儿体外循环（CPB）期间血浆S100蛋白、神经元特异性烯醇化酶（NSE）水平变化及参附注射液的干预作用。方法将36例先天性心脏病患儿随机分为参附组和对照组各18例,CPB前分别微量泵注射参附注射液1ml／kg和等量生理盐水,于麻醉诱导后即刻（T1）、CPB开始时（T2）、主动脉阻断时（T3）、CPB20min时（T4）、CPB结束时（T5）及术后6h（T6）、24h（T7）抽取中心静脉血．采用ELISA法测定血浆中S100蛋白、NSE。结果两组T4、T5及T6时点血浆S100蛋白、NSE明显高于T1（P〈O．05）;T4时点参附组血浆S100蛋白、NSE明显低于对照组（P〈0．05）。结论婴幼儿CPB期间血浆S100蛋白、NSE水平升高;参附注射液可降低两者水平．具有一定脑保护作用。     

Oxidative stress is exacerbated in diabetic patients during cardiopulmonary bypass

Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery. MATERIAL AND METHODS: Control patients (n=17) and diabetic (type 2) patients (n=13) were included in this study. Blood samples were drawn before, during and after the CPB. Oxidative stress was evaluated in the plasma by direct and indirect approaches. Direct detection of ascorbyl radicals was assessed by electron spin resonance spectroscopy. An index: ascorbyl radical/vitamin C ratio is an indicator of the degree of oxidative stress taking place in the plasma. Oxygen radical absorbing capacity (ORAC) values were used as measurement of antioxidant capacity of the plasma. To determine inflammation profile of patients, we measure the evolution of plasma concentration of interleukin 8 (IL-8). RESULTS: During cross clamping and post-CPB, the index ascorbyl radical/vitamin C is increased; the value of the index is more significant in diabetic patients. Concomitantly, ORAC values decreased in all the patients during cross clamping (p<0.05). Results concerning inflammatory index showed that IL-8 levels increased during the CPB. CONCLUSION: In conclusion, the current study indicates that a systemic oxidative stress occurs during CPB and post-CPB periods and that in patients with type 2 diabetes mellitus, the systemic oxidative stress was increased.     

Obesity is associated with higher mortality in patients with cardiogenic shock

Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction. Studies that have focused on identifying mortality predictors in patients with cardiogenic shock have not evaluated outcomes in obese patients. A study of sixty-one patients with cardiogenic shock demonstrated that obese patients with cardiogenic shock have a higher mortality risk compared to non-obese patients.     

右美托咪定对脓毒症相关性脑病患者炎症因子及S100β蛋白的影响

目的分析右美托咪定和异丙酚对脓毒症相关性脑病(SAE)患者炎性因子及S100β蛋白的影响。方法入选徐州医科大学附属医院重症监护病房(ICU)2017年7月至2018年12月行机械通气的SAE患者50例,随机数表法分为异丙酚组和右美托咪定组,每组25例。分别接受异丙酚和右美托咪定治疗,比较2组患者用药后1 h(T1)、12 h(T2)、24 h(T3)、3 d(T4)白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和中枢神经特异性蛋白S100β水平,以及不良反应、死亡率和留住ICU时间。应用SPSS 20.0统计软件对数据进行分析。依据数据类型,采用t检验或χ2检验进行组间比较。结果右美托咪定组相比异丙酚组患者T2、T3、T4时间点TNF-α[(17.83±2.09)和(19.96±2.65)ng/L;(14.95±3.37)和(18.83±4.46)ng/L;(8.62±3.07)和(17.75±5.06)ng/L]、S100β蛋白[(0.69±0.05)和(0.61±0.04)μg/L;(0.62±0.03)和(0.55±0.03)μg/L;(0.56±0.02)和(0.42±0.01)μg/L]水平低,T3、T4时间点IL-6[(340.71±10.37)和(390.89±12.26)ng/L;(240.62±10.54)和(331.15±12.64)ng/L]水平低,差异均有统计学意义(P<0.05)。右美托咪定组患者1例呼吸抑制,4例心动过缓,2例低血压;异丙酚组患者2例呼吸抑制,3例心动过缓,4例低血压。右美托咪定组相比异丙酚组患者不良反应发生率[28%(7/25)和36%(9/25)]差异无统计学意义(P>0.05)。右美托咪定组患者4例死亡,入住ICU时间(13.19±2.26)d,异丙酚组患者2例死亡,入住ICU时间(13.07±2.16)d,2组预后比较差异均无统计学意义(P>0.05)。结论右美托咪定用于SAE患者可一定程度减轻炎症反应,获得理想的镇静效果。     

Vitronectin (S protein) is associated with platelets

Vitronectin is a plasma glycoprotein that has regulatory activity in the complement and the coagulation systems, in cell-cell and cell-substrate interactions, and in monocyte/macrophage function. Because of its potential to participate in several of the processes of inflammation and repair, the association of vitronectin with platelets was investigated. Immunochemical studies demonstrated that the majority of the platelet associated vitronectin was intracellular, while a relatively modest amount was localized to the ectoplasmic portion of the plasma membrane. Analysis by Western blot showed that the electrophoretic mobility of platelet associated vitronectin was indistinguishable from that of vitronectin isolated from plasma. In response to thrombin, approximately 1 microgram of vitronectin was released into the supernate of 10(9) platelets, while somewhat less than one-half of the total platelet vitronectin remained cell associated. The binding of vitronectin to platelets was investigated by comparing the capacity of unlabelled vitronectin and fibronectin to inhibit binding of radiolabelled fibronectin to thrombin stimulated platelets. On a weight basis, inhibition by the two proteins was equivalent, suggesting that vitronectin competes with fibronectin for binding to platelet glycoprotein IIb/IIIa. These results demonstrate that vitronectin is a platelet specific protein which, because of its multifunctional properties, may participate in physiological and pathophysiological events associated with thrombosis and haemostasis.     

A 100-kDa urinary protein is associated with insulin resistance in offspring of type 2 diabetic patients

Aims/hypothesis One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulin-resistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabetic patients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance.Methods Urinary proteins from timed overnight urine collections from 128 offspring of type 2 diabetic patients and 9 control subjects were analysed by western blotting using an antibody against nephrin. Glucose metabolism was assessed by OGTT and IVGTT and the euglycaemic–hyperinsulinaemic clamp technique.Results Of the offspring, 12.5% were strongly and 14.1% weakly positive for a 100-kDa urinary protein. All controls were negative. During the first 10 min of an IVGTT, the offspring strongly positive for the urinary protein had a higher insulin response than the offspring without the protein (3,700 vs 2,306 pmol l^–1min^–1, p=0.007). Insulin sensitivity (the rate of whole-body glucose uptake divided by the steady-state insulin level×100) was lower among the offspring strongly positive for the urinary protein than among the offspring negative for the protein (11.3 vs 15.8 mol kg^–1min^–1pmol^–1l^–1, p=0.008).Conclusions/interpretation A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabetic patients.     

Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results

STUDY OBJECTIVES: Strokes and neurocognitive dysfunction have been correlated with cerebral microemboli produced during cardiopulmonary bypass (CPB). The purpose of this study was to determine whether, and to what extent, off-pump coronary artery bypass (OPCAB) reduces the occurrence of cerebral microemboli compared with traditional coronary artery bypass grafting (CABG) with CPB and to compare clinical results. DESIGN AND PATIENTS: A retrospective review of 137 patients undergoing elective CABG was performed, 70 of whom underwent traditional CABG and 67 of whom underwent OPCAB. Using transcranial Doppler ultrasonography, 40 patients (20 CABG, 20 OPCAB) were continuously monitored intraoperatively for the occurrence and pattern of cerebral microemboli. SETTING: Private, university-affiliated tertiary care hospitals. RESULTS: There was no statistical difference in the age, sex, or underlying comorbidities between those patients undergoing CABG and OPCAB. CABG patients did have a slightly lower preoperative ejection fraction (50.9% vs 55.5%, p = 0.03). Despite these similar preoperative characteristics, the OPCAB group experienced significant reductions in cerebral microemboli (27 vs 1,766, p = 0.003), transfusion requirements (29.9% vs 47.1%, p = 0.04), intubation time (3.3 vs 9.5 h, p < 0.001), ICU length of stay (1.5 vs 2.8 days, p = 0.02), and overall hospitalization (4.9 vs 6.6 days, p = 0.01) without an increase in mortality. Fewer strokes and deaths were observed in the OPCAB group, but these trends failed to reach statistical significance. CONCLUSIONS: In similar patient populations, OPCAB was associated with significantly fewer cerebral microemboli and improved clinical results without an increase in mortality. We believe that these early results support OPCAB as a viable and potentially safer alternative to traditional CABG.     

艾司洛尔对紫绀型先天性心脏病患儿CPB过程中心肌损伤及能量代谢的影响

目的 探讨艾司洛尔对紫绀型先天性心脏病（CCHD）患儿体外循环（CPB）过程中心肌损伤的影响及机制.方法 将16例行CPB下心内直视术CCHD患儿随机分为观察组和对照组各8例,两组手术方法及麻醉方法均相同,但自麻醉诱导至术毕观察组和对照组分别静脉泵注艾司洛尔3 mg/（kg·h）及等量复方氯化钠溶液.观察两组手术一般情况,并分别于转流前（T1）、主动脉阻断后30 min（T2）、主动脉开放后30 min（T3）、术后24 h（T4）采集中心静脉血,测定肌酸激酶同工酶（CK-MB）、肌钙蛋白I（cTnI）水平,并于T1、T3取右心耳组织测定心肌组织腺甘酸含量及线粒体肿胀度（MSD）.结果 观察组复跳后心律失常发生率、多巴胺用量、ICU滞留时间及术后住院时间均显著小于对照组（P均〈0.05）;与T1时比较,两组T3和T4时血清CK-MB和cTnI水平明显升高、T3时心肌腺苷酸含量显著减少,MSD显著升高（P均〈0.01）,但观察组变化幅度均显著小于对照组（P〈0.05）.结论 艾司洛尔可通过改善心肌能量代谢及线粒体功能等途径减轻CCHD患儿CPB过程中缺血再灌注损伤.     

Survival after surgery with cardiopulmonary bypass in low weight patients

To evaluate risk factors for hospital death in patients weighing < 2.5 kg undergoing open-heart surgery, records of 34 consecutive low-weight patients operated on between December 1997 and November 2004 were reviewed. Mean weight was 2.152 +/- 0.237 kg (range, 1.600 to 2.460 kg). Biventricular repair was achieved in 28 patients. The most frequent procedures were the arterial switch operation in 9 children, ventricular septal defect closure in 6, repair of total anomalous pulmonary venous connection in 5 and truncus arteriosus repair in 5. There were 8 early deaths. Mortality was strongly associated with the Comprehensive Aristotle Complexity Score: mortality was low (2/27; 7.4%) with a score < 19, and high (6/7; 85.7%) with a score >/= 19. Higher mortality was encountered after univentricular repair (4/6; 67%). Hyperlactatemia at the end of cardiopulmonary bypass was also associated with poor survival. A Comprehensive Aristotle score < 19 was the strongest predictor of survival in low-weight patients undergoing open-heart surgery. Biventricular repair, when feasible, should be promoted to improve outcome.     

Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia

Anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia requires the use of other anticoagulants. We report a case in whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our experience and a review of the literature, we provide guidelines for managing these rare patients. A danaparoid dose substantially lower than that recommended by the manufacturer may minimize bleeding complications.     

Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction

Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine (D) and dopamine-nitroprusside (DN) on renal function during cardiopulmonary bypass (CPB). No differences from the control group (C) were found in creatinine clearance, fractional sodium excretion, osmolarity and free-water clearance. Sodium output/ intake ratio during CPB was higher in group D than in groups C and DN (P < 0.05): water output/intake ratio was higher in group D than in group C (P < 0.05). Urine lysozime levels and α-glycosidase/creatinine ratios increased similarly in the three groups, suggesting ischemic tubular cell damage. No patients showed acute postoperative renal failure or a worsening of their renal dysfunction. The data suggest an increased water and sodium excretion during CPB with a dopamine infusion, possibly resulting from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration.     

Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and S100A12 protein

CONTEXT: The interaction of advanced glycation end products, including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) and S100A12 protein, with their cellular receptor (RAGE) is implicated in the pathogenesis of diabetic vascular complications. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which, by neutralizing the action of advanced glycation end products, might exert a protective role against the development of cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether plasma sRAGE levels are associated with glycemic control, proinflammatory factors, or circulating ligands of RAGE such as plasma CML and S100A12 protein. STUDY DESIGN: We studied 160 subjects, 84 subjects with type 2 diabetes (aged 60 +/- 7 yr) and 76 nondiabetic controls (aged 45 +/- 10 yr). RESULTS: Plasma sRAGE was lower in diabetic patients than controls [141 (53-345) vs. 735 (519-1001) pg/ml, median (interquartile range), P < 0.0001], whereas CML levels were higher in diabetic patients than controls [67.9 (46.0-84.7) vs. 43.4 (28.0-65.0) microg/ml, P < 0.0001]. In stepwise regression analysis of the whole data set, hemoglobin A1c, insulin resistance (as homeostasis model assessment), and C-reactive protein were independently associated with plasma sRAGE, whereas age was not. In a subgroup of 26 diabetic and 24 nondiabetic subjects of similar age (54 +/- 3 yr), plasma S100A12 levels were higher in diabetic subjects [49 (39-126) vs. 28 (21-39) ng/ml]. Moreover, low sRAGE and high S100A12 were strongly associated with increased risk for cardiovascular disease (Framingham score). In this subgroup, the plasma S100A12 level was the only determinant of plasma sRAGE concentration. CONCLUSION: Plasma level of sRAGE is down-regulated in chronic hyperglycemia; among its ligands, S100A12 protein, but not CML, appears to be associated with this effect.