Post-Bypass Dexmedetomidine Use and Postoperative Acute Kidney Injury in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Background

And Objectives: The aim of this retrospective investigation was to study the relationships among chronic kidney disease, acute kidney injury (AKI), and potential benefits by post-bypass dexmedetomidine use in patients undergoing cardiac surgery.

Methods

The patient data were reviewed from the institutional Society of Thoracic Surgeons National Adult Cardiac Surgery Database after IRB approval. 1,133 patients were identified and divided into two groups: those who received dexmedetomidine or those who did not during the post-bypass period. The postoperative outcomes include the incidence of AKI, any complication and all cause of mortality.

Results

Post-bypass dexmedetomidine use was associated with significantly reduced the incidence of total AKI (26.1% vs. 33.75%; adjusted OR, 0.7033; 95%CI, 0.540 to 0.916; p=0.0089). In addition, post-bypass dexmedetomidine use was more likely to reduce the incidence of AKI in these patients with preoperative normal kidney function (Stage1; 32.8% to 22.8%; p=0.0233) and mild CKD (Stage 2; 32.8% to 24.7; p=0.0003) after cardiac surgery. Post-bypass infusion of dexmedetomidine was associated with significantly reduced incidence of any complication and 30-day mortalities.

Conclusions

Post-bypass dexmedetomidine use is associated with a significant reduction in the incidence of AKI, especially mild AKI in patients with preoperative normal renal function and mild CKD undergoing cardiac surgery.     

预防心脏手术中体外循环致肺损伤的研究进展

体外循环是心内直视手术的一种重要手段,随着体外循环装置、心肌保护措施和心脏外科技术的不断完善与提高,心内直视手术并发症的发生率和死亡率已大大下降。但肺损伤仍是CPB后的主要并发症之一,而肺损伤后气体交换障碍可能造成严重的并发症,甚至死亡。本文综述了体外循环心脏手术后肺损伤的发生机制及预防措施的研究进展。     

预防心脏手术中体外循环致肺损伤的研究进展

体外循环是心内直视手术的一种重要手段,随着体外循环装置、心肌保护措施和心脏外科技术的不断完善与提高,心内直视手术并发症的发生率和死亡率已大大下降。但肺损伤仍是CPB后的主要并发症之一,而肺损伤后气体交换障碍可能造成严重的并发症,甚至死亡。本文综述了体外循环心脏手术后肺损伤的发生机制及预防措施的研究进展。     

Central-Radial Artery Pressure Gradient after Cardiopulmonary Bypass Is Associated with Cardiac Function and May Affect Therapeutic Direction

Objective

To investigate the risk factors involved in radial-femoral artery pressure gradient after cardiac surgery.

Methods

In this retrospective study, we reviewed 412 cardiac surgeries with both femoral artery pressure and radial artery pressure monitoring before cardiopulmonary bypass. 138 patients had radial-femoral artery pressure gradient after cardiopulmonary bypass (group P) but 263 were not (group N). Their hemodynamic data and other demographic data were analyzed.

Results

Phenylephrine usage was 1.7±1.1 mg in group N and 2.9±1.2 mg in group P (P<0.001). Total adrenaline usage was 229.2±116.9 µg in group N and 400.6±145.1 µg in group P (P<0.001). SBP gradient was -4±3, 14±9, 10±4, 0±11 mmHg in group P and -3±3, 0±1, -1±9, -6±4 mmHg in group N after induction, during discontinuation of CPB, at the end of surgery and 1 postoperative day respectively. DBP gradient was 3±3, -1±9, 4±5, 0±8 mmHg in group P and 3±3, 5±2, 7±5, 0±8 mmHg in group N after induction, during discontinuation of CPB, at the end of surgery and 1 postoperative day respectively. MAP gradient was 1±2, 4±6, 6±4, 0±8 mmHg in group P and 1±2, 3±1, 1±4, -2±5 mmHg in group N after induction, during discontinuation of CPB, at the end of surgery and 1 postoperative day respectively. Significant arterial pressure gradient emerged during discontinuation of CPB and at the end of surgery, which was more obvious in group P(P<0.01). CI was 2.0±0.3, 2.3±0.4,2.3±0.4, 2.2±0.4 L/min/m² in group P and 2.1±0.3, 2.8±0.5,2.8±0.5, 2.8±0.5 L/min/m² in group N at baseline, after discontinuation of CPB, at the end of surgery and the first postoperative day (P<0.001).

Conclusion

Detecting the exact central artery pressure is most important when patients have artery pressure gradients after cardiac surgery. Use inotropic agents to improve cardiac output, avoiding excessive vasoconstriction might reduce artery pressure gradient.     

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

Objective

Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.

Methods

Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.

Results

The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.

Conclusions

HLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.     

围术期应用他汀类药物对冠状动脉旁路移植术并发急性肾损伤疗效的研究进展

急性肾损伤是冠状动脉旁路移植术后常见并且严重的并发症,目前临床治疗主要以对症治疗和肾脏替代治疗为主。作为调节冠心病患者血脂的他汀类药物,其对于行冠状动脉旁路移植术患者肾脏的作用也成为了学者研究的热点问题。目前虽已有充分证据表明他汀类药物可以降低行冠状动脉旁路移植术患者院内死亡率,但是尚不清楚其能否降低患者术后急性肾损伤的发生率。对于在冠状动脉旁路移植术围手术期应用他汀类药物,其应用的时间窗以及应用的剂量学者们仍未达成统一意见。本文通过分析他汀类药物在冠心病整体防治中的作用机理机制,以及总结近几年关于他汀用药时间窗,用药剂量对于行CABG患者术后肾脏影响的相关文献,对围手术期应用他汀类药物对于行CABG患者术后急性肾损伤的影响展开综述。     

Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury after Pediatric Cardiac Surgery

Background

The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).

Methods

We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.

Results

12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)²/1000) (SE 0.4) vs 0.47 ((ng/ml)²/1000) (SE 0.1), respectively; p<0.05). Urinary [TIMP-2]•[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85. Sensitivity was 0.83, and specificity was 0.77 for a cutoff value of 0.70 ((ng/ml)²/1000).

Conclusions

Urinary [TIMP-2]•[IGFBP7] represent sensitive, specific, and highly predictive early biomarkers for AKI after surgery for congenital heart disease.

Trial Registration

www.germanctr.de/, DRKS00005062     

心脏手术围术期的血糖波动与术后急性肾损伤

心脏手术围术期高血糖与术后并发症的关系已经得到大量研究,高血糖与术后肾功能损伤的关系存在着不同的观点,但是对于围术期血糖水平的波动与术后肾损伤的研究甚少。本文概述了心脏手术围术期血糖水平波动对术后肾功能损伤的影响,简要分析其损伤机制。研究表明,多种因素可以增加围术期血糖水平的波动,对多项围术期高血糖是否增加术后肾功能损伤的研究争议分析发现,围术期血糖水平的波动对术后肾损伤的发生起到潜在作用,其损伤机制主要在于引起氧化应激和血流动力学的波动。相信围术期血糖水平的波动对术后肾功能损伤的影响的进一步的研究,将有助于降低心脏手术后急性肾损伤患者术后并发症的发生率。     

Hospital Admission following Acute Kidney Injury in Kidney Transplant Recipients Is Associated with a Negative Impact on Graft Function after 1-Year

The incidence and outcomes of acute kidney injury (AKI) in kidney transplantation are poorly known. Retrospective cohort analysis was performed on the data of all patients (≥3 months after transplantation and ≥16 years of age) admitted to the hospital due to medical or surgical complications from 2007 to 2010. We analyzed 458 kidney transplant recipients, 55.2% men, median age 49 (IQR, 36–58) years, median of 12.5 (IQR, 3–35) months after kidney transplantation; admitted to the hospital due to medical or surgical complications. Most of the patients received a kidney from a deceased donor (62.2%), the primary cause for hospital admission was infection (60.7%) and 57 (12.4%) individuals were diagnosed with acute rejection (AR). The incidence of AKI was 82.3%: 31.9% stage 1, 29.3% stage 2 and 21.2% stage 3. Intensive care unit (ICU) admission (OR 8.90, 95% CI: 1.77–44.56 p = 0.008), infection (OR 5.73, 95% CI: 2.61–12.56, p<0.001) and the use of contrast media (OR 9.34, 95% CI: 2.04–42.70, p = 0.004) were the independent risk factors for AKI development. The mortality rate was 2.1% and all patients who died were diagnosed with AKI. Even after the exclusion of AR cases, at the end of 12 months, the individuals with AKI exhibited higher percent changes in creatinine values when compared with individuals without AKI (9.1% vs. -4.3%; p<0.001). According to KDIGO system, we found a high incidence of AKI among the complications of renal transplantation. As in other scenarios, AKI was associated with renal function loss at 1-year after the hospital discharge.     

Cardiac Compression of Lung Lower Lobes after Coronary Artery Bypass Graft with Cardiopulmonary Bypass

Background

Atelectasis is a major cause of hypoxemia after coronary artery bypass grafting (CABG) and is commonly ascribed to general anesthesia, high inspiratory oxygen concentration and cardiopulmonary bypass (CPB). The objective of this study was to evaluate the role of heart-induced pulmonary compression after CABG with CPB.

Methods

Seventeen patients without pre-operative cardiac failure who were scheduled for coronary artery bypass graft underwent pre- and postoperative thoracic computed tomography. The cardiac mass, the pressure exerted on the lungs by the right and left heart and the fraction of collapsed lower lobe segments below and outside of the heart limits were evaluated on a computed tomography section 1 cm above the diaphragmatic cupola.

Results

In the postoperative period, cardiac mass increased by 32% (117±31 g versus 155±35 g, p<0.001), leading to an increase in the pressure that was exerted on the lungs by the right (2.2±0.6 g.cm⁻² versus 3.2±1.2 g.cm⁻², p<0.05) and left heart (2.4±0.7 g.cm⁻² versus 4.2±1.8 g.cm⁻², p<0.001). The proportion of collapsed lung segments beneath the heart markedly increased [from 6.7% to 32.9% on the right side (p<0.001) and from 6.2% to 29% on the left side (p<0.001)], whereas the proportion of collapsed lung segments outside of the heart limits slightly increased [from 0.7% to 10.8% on the right side (p<0.001) and from 1.5% to 12.6% on the left side (p<0.001)].

Conclusion

The pressure that is exerted by the heart on the lungs increased postoperatively and contributed to the collapse of subjacent pulmonary segments.     

Growth Differentiation Factor-15 (GDF-15) Levels Are Associated with Cardiac and Renal Injury in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass

Objective

Growth differentiation factor-15 (GDF-15) has been identified as a strong marker of cardiovascular disease; however, no data are available concerning the role of GDF-15 in the occurrence of organ dysfunction during coronary artery bypass grafting (CABG) associated with cardiopulmonary bypass (CPB).

Methods

Five arterial blood samples were taken sequentially in 34 patients from anesthesia induction (IND) until 24 h after arrival at the intensive care unit (ICU). Plasma levels of GDF-15, follistatin-like 1 (FLST1), myeloperoxidases (MPO), hydroperoxides and plasma antioxidant status (PAS) were measured at each time-point. Markers of cardiac (cardiac-troponin I, cTnI) and renal dysfunction (neutrophil gelatinase-associated lipocalin, NGAL) and other classical biological factors and clinical data were measured.

Results

Plasma GDF-15 levels increased gradually during and after surgery, reaching nearly three times the IND levels in the ICU (3,075±284 ng/L vs. 1,061±90 ng/L, p<0.001). Plasma MPO levels increased dramatically during surgery, attaining their highest level after unclamping (UNCLAMP) (49±11 ng/mL vs. 1,679±153 ng/mL, p<0.001) while PAS significantly decreased between IND and UNCLAMP (p<0.05), confirming the high oxidative status induced by this surgical procedure. ICU levels of GDF-15 correlated positively with cTnI and NGAL (p = 0.006 and p = 0.036, respectively), and also with hemoglobin and estimated glomerular filtration rate (eGFR). Among all the post-operative biomarkers available, only eGFR, NGAL and GDF-15 measured at ICU arrival were significantly associated with the onset of acute kidney injury (AKI). Patients with a EuroSCORE >3 were shown to have higher GDF-15 levels.

Conclusions

During cardiac surgery associated with CPB, GDF-15 levels increased substantially and were associated with markers of cardiac injury and renal dysfunction.     

Urinary Biomarkers TIMP-2 and IGFBP7 Early Predict Acute Kidney Injury after Major Surgery

Objective

To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients.

Introduction

Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.

Methods

In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.

Results

107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001).

Conclusions

Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.     

患儿体外循环直视心脏术后高尿酸血症分析

目的：探讨体外循环心脏术后24h患儿高尿酸血症发生的原因、影响因素和预后。方法：以2006年9～12月我院心脏外科收治的106例体外循环心脏手术患儿为研究对象,收集其年龄、体外循环时间、尿量、预后资料和心脏术后24h血尿酸、尿素氮、肌酐、胱抑素、血糖、总胆红素、直接胆红素等生化指标数据;以空腹血尿酸为标准,将患儿分为无高尿酸血症组和高尿酸血症组,用SPSS11．0软件分析两组之间临床资料的差异、高尿酸血症组血尿酸与其他指标的相关性及影响患者预后的因素。结果：患儿术后高尿酸血症组患者53例（50％）,与无高尿酸血症组相比P〈0．01,除年龄因素外,其他临床指标均有统计学意义;高尿酸血症组的血尿酸与血糖、总胆红素无相关性,与年龄、尿量呈显著负相关,与转流时间、尿素氮、肌酐、胱抑素、直接胆红素含量呈极显著正相关;在预后良好组与死亡组的比较中,转流时间、血尿酸、尿素氮、肌酐含量有统计学意义。结论：患儿体外循环心脏术后高尿酸血症的发生较常见,血尿酸水平对患者术后肾功能状态及预后具有重要临床意义,连续监测术后血尿酸、尿素氮、肌酐水平是及时判断患者临床状况以采取相应措施改善预后的重要方法;低心排血量综合征是引起患者死亡的危险因素之一,通过提高体外循环心脏手术水平,尽量缩短转流时间,加强围手术期监护,可有效减少术后并发症,降低死亡率。     

Nitrotyrosine Level Was Associated with Mortality in Patients with Acute Kidney Injury

Background

To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI.

Methodology/Principal Findings

158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score.

Conclusions/Significance

There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness.     

Prognostic Value of Acute Kidney Injury after Cardiac Surgery according to Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) Criteria

Objectives

The definition of acute renal failure has been recently reviewed, and the term acute kidney injury (AKI) was proposed to cover the entire spectrum of the syndrome, ranging from small changes in renal function markers to dialysis needs. This study was aimed to evaluate the incidence, morbidity and mortality associated with AKI (based on KDIGO criteria) in patients after cardiac surgery (coronary artery bypass grafting or cardiac valve surgery) and to determine the value of this feature as a predictor of hospital mortality (30 days).

Methods

From January 2003 to June 2013, a total of 2,804 patients underwent cardiac surgery in our service. Cox proportional hazard models were used to determine the association between the development of AKI and 30-day mortality.

Results

A total of 1,175 (42%) patients met the diagnostic criteria for AKI based on KDIGO classification during the first 7 postoperative days: 978 (35%) patients met the diagnostic criteria for stage 1 while 100 (4%) patients met the diagnostic criteria for stage 2 and 97 (3%) patients met the diagnostic criteria for stage 3. A total of 63 (2%) patients required dialysis treatment. Overall, the 30-day mortality was 7.1% (2.2%) for patients without AKI and 8.2%, 31% and 55% for patients with AKI at stages 1, 2 and 3, respectively. The KDIGO stage 3 patients who did not require dialysis had a mortality rate of 41%, while the mortality of dialysis patients was 62%. The adjusted Cox regression analysis revealed that AKI based on KDIGO criteria (stages 1–3) was an independent predictor of 30-day mortality (P<0.001 for all. Hazard ratio = 3.35, 11.94 and 24.85).

Conclusion

In the population evaluated in the present study, even slight changes in the renal function based on KDIGO criteria were considered as independent predictors of 30-day mortality after cardiac surgery.     

体外循环心脏手术患者肝功能的表达水平及腺苷蛋氨酸的干预机制研究

目的:探讨体外循环心脏手术患者肝功能的表达水平及腺苷蛋氨酸的干预机制。方法:选取2017年5月至2018年6月在海南医学院第二附属医院接受体外循环心脏手术的患者184例,根据随机数字表法分为观察组及对照组各92例,分别比较术前、术后所有患者肝功能指标水平。术后对照组患者给予生理盐水干预7d,观察组患者给予腺苷蛋氨酸干预7d,比较两组患者干预7d后肝功能指标、炎症反应指标以及心肌损伤指标水平。结果:术前患者的总胆红素(TBI)、直接胆红素(DBI)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平均显著低于术后,差异均有统计学意义(P0.05)。干预7d后观察组患者的TBI、DBI、ALT、AST、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、肌酸激酶同工酶(CK-MB)、肌钙蛋白(cTnT)水平均显著低于对照组,而白细胞介素-10(IL-10)水平显著高于对照组,差异均有统计学意义(P0.05)。观察组不良反应发生率为7.61%(7/92),与对照组的2.17%(2/92)相比,差异无统计学意义(P0.05)。结论:体外循环心脏手术会对患者肝功能造成一定程度的损害,而腺苷蛋氨酸对患者的肝功能以及心肌组织均有一定的保护作用,同时能减轻炎症反应程度,无严重药物不良反应发生。     

Cardiopulmonary Bypass during Cardiac Surgery Modulates Systemic Inflammation by Affecting Different Steps of the Leukocyte Recruitment Cascade

Background

It is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB.

Methods

We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis.

Results

CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils.

Conclusion

These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.