体外循环下冠状动脉旁路移植术中性粒细胞表面黏附分子表达水平的临床观察

目的 以心肌肌钙蛋白Ⅰ（cTnⅠ）作为心肌损伤的标志物,观察心肌缺血-再灌注损伤期中性粒细胞表面黏附分子CD11b冠脉循环和外周循环的表达水平.方法 选取12例择期进行冠状动脉旁路移植手术（CABG）者,分别于CPB开始前、CPB中和主动脉开放后,经冠脉循环和体循环同时取血,测定中性粒细胞表面CD11b平均荧光强度和血清cTnⅠ浓度.结果 冠脉循环和体循环血cTnⅠ浓度在主动脉开放后均明显升高（P＜0.05）;CPB期间和主动脉开放后,体循环血CD11b含量不断升高,而冠脉循环内CD11b含量则呈现下降趋势,二者间差异有统计学意义（P＜0.05）.结论 体外循环期间,存在心肌缺血-再灌注损伤.激活的中性粒细胞有冠脉滞留效应,中性粒细胞表面CD11b表达水平在冠脉循环中下降,在体循环中升高,出现分离现象,此时单纯以冠脉循环内CD11b表达水平判定心肌缺血再灌注损伤并不全面.     

Simvastatin blunts the increase of circulating adhesion molecules after coronary artery bypass surgery with cardiopulmonary bypass

OBJECTIVES: Endothelial dysfunction has been shown to be a critical early component of organ injury after myocardial ischemia and reperfusion. Circulating levels of adhesion molecules have been regarded as a valid index of endothelial activation. Recent reports suggest that statins, widely used in the control of hypercholesterolemia, exert a protective effect on the endothelium reflected by a reduced level of circulating adhesion molecules. In this study, the effects of preoperative simvastatin treatment, at doses equivalent to those used orally for cholesterol control, were studied on plasma levels of VCAM-1, ICAM-1, and ELAM-1. DESIGN: A case-control study. SETTING: University hospital. PARTICIPANTS: Fifteen patients taking simvastatin with good control of cholesterol levels, 15 patients not responsive to the simvastatin treatment, and 15 normocholesterolemic patients (control) undergoing elective coronary artery bypass surgery. MEASUREMENTS AND MAIN RESULTS: The plasma levels of VACM-1, ICAM-1, and ELAM-1 were evaluated at baseline; during cardiopulmonary bypass; and 6 hours, 24 hours, and 48 hours postoperatively. In the late postoperative samples, the plasma levels of ICAM-1 and ELAM-1 were lower in both simvastatin-treated patients compared with the control patients. No significant difference was found between the patients responsive to statin and those not responsive. Finally, no significant difference was found for VCAM-1 plasma levels between the control group and the 2 treatment groups. CONCLUSIONS: Pretreatment with simvastatin significantly reduces the increase of ICAM-1 and ELAM-1 after coronary artery bypass surgery, by a mechanism that seems not related to its efficacy in lowering cholesterol levels.     

Leukocyte depletion attenuates expression of neutrophil adhesion molecules during cardiopulmonary bypass in human beings

BACKGROUND: On the basis of scanty information, the effects of a leukocyte filter during cardiac operations in human beings have been examined from the viewpoint of the expression of neutrophil adhesion molecules. This study was therefore designed to determine whether leukocyte depletion during cardiopulmonary bypass may interfere with neutrophil adhesion properties. METHODS: Twenty-four patients undergoing elective heart operations were randomly allocated to a leukocyte-depletion group or a control group. Blood samples were collected at 7 points: before sternotomy, at 10, 30, and 60 minutes of cardiopulmonary bypass, at termination of cardiopulmonary bypass, 5 minutes after protamine administration, and 2 hours after cardiopulmonary bypass. The expression of the neutrophil surface adhesion molecules L-selectin and beta2-integrins was determined by flow cytometric analysis in whole blood. RESULTS: (1) CD11a expression did not change significantly in either group. There were no significant differences between control and leukocyte-depletion groups (P =.63). (2) There was a significantly higher expression of CD11b on the neutrophils during cardiopulmonary bypass in the control group than in the leukocyte-depletion group (P =.01). (3) CD11c expression was initially up-regulated from the onset of cardiopulmonary bypass, reaching a peak at 60 minutes after bypass in the control group (P =.02). The expression of CD11c did not differ significantly between groups (P =.23). (4) L-selectin expression was significantly lower in the leukocyte-depletion group than in the control group (P =.03). CONCLUSIONS: The major findings of the present study in human subjects undergoing elective cardiac operations with cardiopulmonary bypass are as follows: (1) bypass was associated with an up-regulation of the adhesion molecules L-selectin, CD11b, and CD11c but with no significant change in CD11a expression, and (2) the clinical use of a leukocyte-depleting filter could down-regulate the expression of CD11b and L-selectin.     

Soluble adhesion molecules in coronary surgery and cardiopulmonary bypass with pump prime aprotinin

OBJECTIVE: The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. DESIGN: Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. RESULTS: There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin (p = 0.21) and sICAM-1 (p = 0.91). CONCLUSION: Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.     

Inhibition by dipyridamole of neutrophil adhesion to vascular endothelium during coronary bypass surgery.

BACKGROUND: Release of reactive oxygen radicals by activated neutrophils and neutrophil adhesion to endothelial cells have been observed after cardiopulmonary bypass. The aim of the present study was to evaluate the effects of preoperative dipyridamole treatment on neutrophil superoxide anion generation and endothelial cell-neutrophil interactions. METHODS: Two groups of patients scheduled for elective coronary artery bypass grafting were randomized to receive oral dipyridamole or a placebo. Nitro blue tetrazolium scores of circulating neutrophils, neutrophil CD11b/CD18 expression, and their adhesion to human umbilical vein endothelial cells were assayed before anesthesia, 30 minutes after the beginning of cardiopulmonary bypass, at the end of bypass, and 60 minutes postoperatively. RESULTS: In both groups, cardiopulmonary bypass resulted in a significant increase in nitro blue tetrazolium scores in circulating neutrophils as well as a significant increase in both neutrophil CD11b/CD18 expression and neutrophil adhesion to endothelial cells. The extent of neutrophil superoxide anion generation was higher in the control group; a significant (p < 0.01) reduction in neutrophil adhesion to endothelial cells was observed 1 hour postoperatively in the dipyridamole group. In 5 patients treated with dipyridamole, the incubation of activated polymorphonuclear leukocytes with adenosine deaminase significantly increased their adhesion to endothelial cells (p < 0.05). CONCLUSIONS: Our study demonstrated that preoperative treatment with oral dipyridamole significantly reduces both neutrophil superoxide anion generation and extent of neutrophil adhesion to endothelial cells after coronary bypass grafting procedures with cardiopulmonary bypass. The mechanism is probably mediated by endogenous adenosine.     

Neutrophil adhesion molecule expression and serum concentration of soluble adhesion molecules during and after pediatric cardiovascular surgery with or without cardiopulmonary bypass

BACKGROUND: Increased neutrophil activation by cardiopulmonary bypass (CPB) during cardiovascular surgery is thought to be responsible for postoperative complications. In children, the contribution of cardiovascular surgery alone to this response is not well-characterized. METHODS: Children undergoing surgery with CPB (CPB group, n = 35) and without CPB (control, n = 22) were studied (age, 3-17 yr). Blood was drawn 24 h preoperatively before medication, after anesthesia, after connection to CPB, at reperfusion, 4 h to 2 days after surgery, at discharge, and months after surgery. Neutrophil antigen expression and serum concentration of adhesion molecules, interleukin 8, and C5a (fragment of C5 complement) were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: With and without CPB, anesthesia and surgery induced decreased LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18), CD45, and CD54 (intercellular adhesion molecule 1) surface expression and sICAM-1 serum concentrations (all P < 0.001). sL-selectin serum concentration decreased with CPB (P < 0.001) but was not significantly altered in the control. In contrast, CD62L expression increased during CPB (P < 0.001). The time course of all analyzed markers was not significantly different between CPB and control, with the exception of sL-selectin (P = 0.017). One-day preoperative baseline values were reached days to months after surgery. Interleukin 8 and C5a serum concentrations increased after surgery in both the CPB group and the control group. CONCLUSIONS: Pediatric cardiovascular surgery leads to reduced adhesiveness and activity of circulating neutrophils. This reduction is more pronounced and sustained with CPB. These data may be useful in the assessment of novel therapeutic strategies.     

Effects of cardiopulmonary bypass on glucose homeostasis after coronary artery bypass surgery.

OBJECTIVE: Hyperglycaemia is associated with increased mortality and morbidity after cardiac surgery. While surgical stress results in hyperglycaemia after all operations, it has been suggested that cardiopulmonary bypass is the dominating contributor after cardiac surgery. This study aimed to determine the contribution of cardiopulmonary bypass to hyperglycaemia after coronary artery bypass. METHODS: Patients scheduled for primary coronary artery bypass grafting were randomised to surgery with or without cardiopulmonary bypass. All patients received continuous insulin infusions during the initial 24-h period. Glucose was infused (100mg/kg per h) postoperatively in the intensive care unit but not during surgery. Blood glucose was measured 4 times daily until the third postoperative day. Serum insulin, insulin-like growth factor-1 and its binding protein were determined. RESULTS: Average blood glucose during the day of surgery did not differ between groups, but 30% more insulin (P=0.003) was required when cardiopulmonary bypass was used. Blood glucose 2-3h after meals was higher in patients using cardiopulmonary bypass during the first 3 postoperative days. Fasting blood glucose was still equally elevated 20-30% in both groups on the third postoperative day. Insulin-like growth factor-1 decreased more (P=0.01) and insulin-like growth factor binding protein-1 increased more (P<0.001) with cardiopulmonary bypass than without. The ratio of insulin-like growth factor-1 concentration to the concentration of its binding protein-1 was more negative (indicating greater catabolism) with cardiopulmonary bypass than without both postoperatively (P=0.002) and on the third postoperative day (P=0.02). Insulin-like growth factor-1 standard deviation score, also a measure of catabolism, was greater after surgery with cardiopulmonary bypass than without (P=0.02). CONCLUSIONS: Glucose homeostasis is disturbed preoperatively for many non-diabetic patients undergoing coronary bypass surgery. Cardiopulmonary bypass exacerbates the catabolism and disturbed glucose homeostasis that is induced also to a lesser degree by surgery without cardiopulmonary bypass.     

The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery

BACKGROUND: Acute renal injury is a common serious complication of cardiac surgery. Moderate hemodilution is thought to reduce the risk of kidney injury but the current practice of extreme hemodilution (target hematocrit 22% to 24%) during cardiopulmonary bypass (CPB) has been linked to adverse outcomes after cardiac surgery. Therefore we tested the hypothesis that lowest hematocrit during CPB is independently associated with acute renal injury after cardiac surgery. METHODS: Demographic, perioperative, and laboratory data were gathered for 1,404 primary elective coronary bypass surgery patients. Preoperative and daily postoperative creatinine values were measured until hospital discharge per institutional protocol. Stepwise multivariable linear regression analysis was performed to determine whether lowest hematocrit during CPB was independently associated with peak fractional change in creatinine (defined as the difference between the preoperative and peak postoperative creatinine represented as a percentage of the preoperative value). A p value of less than 0.05 was considered significant. RESULTS: Multivariable analyses including preoperative hematocrit and other perioperative variables revealed that lowest hematocrit during CPB demonstrated a significant interaction with body weight and was highly associated with peak fractional change in serum creatinine (parameter estimate [PE] = 4.5; p = 0.008) and also with highest postoperative creatinine value (PE = 0.06; p = 0.004). Although other renal risk factors were significant covariates in both models, TM50 (an index of hypotension during CPB) was notably absent. CONCLUSIONS: These results add to concerns that current CPB management guidelines accepting extreme hemodilution may contribute to postoperative acute renal and other organ injury after cardiac surgery.     

Perturbations in laboratory values after coronary artery bypass graft surgery with cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to describe the sequential changes in commonly obtained laboratory values after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: The authors examined laboratory data from 375 patients who underwent uncomplicated CABG with CPB in a multicenter clinical trial of a medication for postoperative pain. Data were obtained preoperatively, at the time of postoperative extubation, and at 4 subsequent intervals ending 14 days after extubation. Data obtained before study drug administration are reported for all patients; thereafter, only data from placebo patients without perioperative complications (n=123) are reported. RESULTS: Mean postoperative coagulation values remained within their reference ranges at the time of extubation. However, platelet counts increased to a peak value well above the reference range by the end of the study. Postoperative white blood cell counts rose above the reference range, mainly because of increased neutrophils. Serum chemistries were also altered; most patients showed a persistent postoperative hyperglycemia. Creatine kinase levels rose to nearly 4 times the upper limit of the reference range in the early postoperative period. Lactate dehydrogenase, serum aspartate aminotransferase, and alanine aminotransferase levels also increased above the reference range. Total protein and albumin values were below the reference range throughout the postoperative period. CONCLUSIONS: Laboratory values for hematology, blood coagulation, and serum chemistry change substantially after uncomplicated CABG with CPB. Recognition of these changes will facilitate the conduct of clinical research and may prevent inappropriate treatment based on abnormal laboratory findings that have no clinical significance.     

Predictors of inotropic support during weaning from cardiopulmonary bypass in coronary artery bypass grafting surgery

Early or prophylactic inotropic drug administration is occasionally required to facilitate separation from cardiopulmonary bypass (CPB) in cardiac surgery. However, it is not without untoward effects and should be conducted on the basis of rational criteria. The purpose of our study was to clarify variables associated with the requirement for inotropic support during separation from CPB and to testify whether pre-CPB left ventricular (LV) function, as evaluated by transesophageal echocardiography (TEE), is one of the significant variables. Clinical profile data and TEE findings were retrospectively analyzed for 91 patients who had received elective primary isolated coronary artery bypass grafting (CABG) surgery. Post-CPB inotropic drug administration initiated prior to aortic decannulation was considered inotropic support for terminating CPB. Stepwise multiple logistic regression analysis identified pre-CPB LV regional wall motion abnormalities (RWMA), NYHA class, age, and duration of CPB (in order of significance) as factors associated with inotropic support for discontinuing CPB. Pre-CPB LV enddiastolic area or fractional area change was not a significant variable in the multivariate model. Our result suggests that evaluation of pre-CPB LV RWMA is useful in predicting the need of inotropic intervention during separation from CPB in patients undergoing CABG surgery. This study was performed at The Weiler Hospital of The Albert Einstein College of Medicine, and was presented in part at the 17th annual meeting of The Society of Cardiovascular Anesthesiologists, Philadelphia, Pennsylvania, May 8–10, 1995     

Inhibition of neutrophil apoptosis after coronary bypass operation with cardiopulmonary bypass

BACKGROUND: Granulocyte apoptosis is a key control process in the clearance of neutrophils from inflammatory sites, and its rate is modulated both in vitro and in vivo by a number of inflammatory mediators. In this study, we investigated the influence of cardiopulmonary bypass (CPB) on neutrophil apoptosis. METHODS: Twenty patients undergoing coronary operation with CPB were studied. Patients undergoing off-pump (OP) coronary bypass and healthy subjects served respectively as stressed and normal groups. Interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha were assessed on plasma collected preoperatively, at the end of CPB, and after intervals of 4, 8, 12, and 24 hours. Neutrophil apoptosis was detected by light microscopy as well as by the annexin-V assay on postoperative samples. The polymorphonuclear leukocyte (PMN) apoptotic receptors, Fas and FasL, were studied together with the activity of caspase 3 in postoperative neutrophils. RESULTS: Spontaneous apoptosis was significantly delayed in PMNs from CPB patients when compared with either the stressed or control patients. Neutrophils were activated, as indicated by increased surface expression of CD11b. Western blot analysis showed a normal expression of the apoptotic receptors Fas and FasL. Caspase 3 activity was found to be significantly reduced in neutrophils from CPB patients after 18 and 24 hours of culture. When control neutrophils were cultured in the presence of postoperative plasma from OP and CPB patients, apoptosis was significantly delayed. Depleting surgical plasma of IL-6 and IL-8 completely abolished this antiapoptotic effect. CONCLUSIONS: Inflammatory mediators during CPB prolong the functional lifespan of neutrophils through modulation of apoptosis, and potentiate the inflammatory response observed after coronary bypass operation.     

Myocardial preservation during coronary surgery with and without cardiopulmonary bypass

BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), although the preservation of the myocardium under such circumstances has not been properly investigated. The aim of this randomized study was to compare the changes in myocardial metabolism during CABG with and without CPB. METHODS: Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients (11 with and 11 without CPB). RESULTS: The maximum myocardial lactate production was significantly higher (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17 mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085 and 0.034 with and without CPB, p = 0.007). The postoperative peak values of creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2 microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent antegrade mild hypothermic blood cardioplegia.     

Reoperative coronary surgery with and without cardiopulmonary bypass.

BACKGROUND: Reoperative coronary surgery without cardiopulmonary bypass (CPB) was analyzed to evaluate the technical profile of the patients studied and the benefit from this technique. MATERIAL AND METHODS: From November 21, 1994 to May 20, 1999, 166 patients had reoperative coronary surgery, 112 patients (Group A) with and 54 patients (Group B) without CPB. Median sternotomy was used in all the patients in Group A and in 13 patients in Group B. The remaining had a LAST (37 patients) or a posterolateral thoracotomy (4 patients). RESULTS: Anastomoses per patient were 2.4 +/- 0.8 in Group A and 1.1 +/- 0.4 in Group B (p < 0.001). When a single graft was needed, CPB was not used in 82.8% of the cases. However, when more than one graft was required, CPB was not used in only 5.6% of the cases. When a single territory had to be grafted, CPB was not used in 76.6% of the patients. If two territories were grafted, only 6.8% of the patients were in Group B, whereas no patient who needed a graft in all the three territories was in Group B. Overall mortality was 3.6% cerebrovascular accident (CVA) and acute myocardial infarction (AMI) incidence were 0.6% and 1.8%, respectively, and were similar in both groups. Incidence of early major events (overall 8.4%) was not different between groups. CONCLUSIONS: The primary endpoints (mortality, CVA rate, and AMI) were similar in both groups, but patients in Group B were less complicated. However, patients in the two groups were not the same, as the technical profile was quite different. As our results were similar to those obtained in the first operation, we think that consideration of different surgical possibilities, depending on territory to be grafted, will improve the results of redo coronary surgery, making them similar to those obtained in the first operation.