Enhanced responsiveness of circulatory neutrophils after cardiopulmonary bypass: increased aggregability and superoxide producing capacity

Cardiac surgery with cardiopulmonary bypass (CPB) induces a whole body inflammatory response that sometimes leads to postoperative organ dysfunction, and neutrophil activation plays an important role in this reaction. Neutrophil priming has been described as a change in neutrophil status such that neutrophils show enhanced responsiveness to a second activating stimulus. We hypothesized that neutrophil priming occurs by cardiac surgery with CPB and is temporally related to the neutrophilia after surgery. To evaluate primed circulatory neutrophil status, we measured aggregation activity stimulated by N-formyl-methyl-leucyl-phenyl-alanine (FMLP) and free radical producing activity by tumor necrosing factor (TNF) alpha in peripheral blood samples. Eleven adult patients undergoing elective cardiac surgery with CPB were studied. Blood samples were taken before surgery, at the end of bypass, 12 h after surgery, and 7 days after surgery. Aggregation activity and superoxide generation were significantly elevated 12 h after surgery when compared to presurgery values, indicating that cardiac surgery is associated with circulatory neutrophil priming. The number of neutrophils markedly increased at the end of cardiopulmonary bypass and reached a peak 12 h after surgery. The circulatory neutrophils of cardiac surgical patients become primed after surgery, coincident with the peak neutrophil count. These results suggest that circulatory neutrophils after cardiac surgery with CPB have enhanced responsiveness and are predisposed to systemic inflammation.     

Neutrophil-mediated secretion and activation of matrix metalloproteinase-9 during cardiac surgery with cardiopulmonary bypass

Cardiopulmonary bypass (CPB) induces neutrophil activation, degranulation, and a systemic inflammatory response. Matrix metalloproteinase (MMP)-9 exists in neutrophils and is released on neutrophil activation. Increased levels of MMP-9 have been observed in patients undergoing CPB. We designed the present study to determine whether MMP-9 is derived from neutrophils during CPB. Twenty-one patients undergoing elective coronary artery bypass grafting with or without CPB were included in this study. Blood was collected and analyzed for MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Neutrophils were also isolated and examined for MMP-9 production and mRNA expression. Plasma levels and activity of MMP-9 increased significantly 2-6 h after beginning CPB, whereas the MMP-9 levels in patients with off-pump cardiac surgery did not increase. The neutrophil content of MMP-9 and mRNA increased significantly 2 h after beginning CPB. The plasma levels of TIMP-1 increased gradually for 6 h, whereas the MMP-9/TIMP-1 ratios were increased 2-4 h after beginning CPB. The present study demonstrated that CPB causes an increase in the concentration and activity of plasma MMP-9. The corresponding increase in neutrophil MMP-9 expression and production suggests that MMP-9 is derived primarily from neutrophils and may contribute to the inflammatory response associated with CPB.     

Prostaglandin E1 infusion fails to inhibit the increase of serum granulocyte elastase and myeloperoxidase and the decrease of plasma angiotensin converting enzyme in patients undergoing open-heart surgery]

We studied whether prostaglandin E1 (PGE1) could inhibit the increase of serum granulocyte elastase (GEL) and myeloperoxidase (MPO), and the decrease of plasma angiotensin converting enzyme (ACE) induced by oxygenator in 19 patients undergoing open-heart surgery. The patients were randomly allocated into 2 groups: one group (PGE1 group, n = 9) received a continuous infusion of PGE1 at a rate of 30 ng.kg-1.min-1 during cardiopulmonary bypass (CPB), and the other group (control group, n = 10) received saline infusion. GEL, MPO and ACE were measured serially at 8 points: before induction of anesthesia (as baseline), immediately before initiation of CPB, 10 min after initiation, 60 min after initiation, immediately after the end of CPB, 60 min after CPB, 120 min after CPB, and on the first postoperative day. Serum levels of GEL and MPO during 120 min after the end of CPB in both groups increased significantly compared with the baseline values. There was no significant difference between the two groups. Plasma levels of ACE in both groups decreased significantly immediately after the end of CPB compared with values taken 10 min after the initiation of CPB. There was no significant difference between the groups. We conclude that the infusion of PGE1 30 ng.kg-1.min-1 failed to inhibit the increase of GEL as well as MPO, and the decrease of ACE.     

Ketamine attenuates neutrophil activation after cardiopulmonary bypass

Surgery is associated with activation of neutrophils and their influx into affected tissue. The pathogenic role of superoxide production generated by activated neutrophils has been documented repeatedly. Ketamine suppresses neutrophil oxygen radical production in vitro. In the present study, we compared the effect of adding small-dose ketamine to opioids during the induction of general anesthesia on superoxide production by neutrophils after coronary artery bypass grafting (CABG). Thirty-five patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blinded manner. The patients received either ketamine 0.25 mg/kg or a similar volume of saline in addition to large-dose fentanyl anesthesia. Blood samples were drawn before the operation, immediately after cardiopulmonary bypass, 24 and 48 postoperative h, and on postoperative Days 3-6. Functional capacity of neutrophils was assessed by superoxide generation after stimulation with phorbol 12-myristate 13-acetate, opsonized zymosan, or formyl-methionyl-leucyl-phenylalanine. The addition of small-dose ketamine to general anesthesia attenuates increased production of the superoxide anion (O2-) by neutrophils without chemical stimulation and after stimulation with phorbol 12-myristate 13-acetate, formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan for 4-6 days after CABG. In addition, ketamine attenuated the percentage of neutrophils on postoperative Days 2-6. In the Control group, superoxide production significantly increased compared with the baseline value. By contrast, in the Ketamine group, this difference was not significant. IMPLICATIONS: In a randomized, double-blinded, prospective clinical study, we compared the effect of adding small-dose ketamine to opioids during general anesthesia on superoxide production and showed that ketamine suppressed the increase of superoxide anion production by neutrophils after coronary artery bypass grafting.     

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.     

Insulin increases neutrophil count and phagocytic capacity after cardiac surgery

We previously reported that a continuous insulin infusion improves neutrophil phagocytic function after cardiac surgery in diabetic patients. These data suggested that hyperglycemia impairs neutrophil function, and because nondiabetic patients also experience hyperglycemia during cardiac surgery, we hypothesized that a continuous insulin infusion would improve glucose control and neutrophil function in nondiabetic cardiac surgical patients. Patients were randomized to receive either no insulin (Control group) or a continuous insulin infusion (Insulin group), with glucose measurements every 10 min during cardiopulmonary bypass (CPB). Blood glucose was significantly lower in the Insulin group immediately after surgery but not during surgery. When assessed as the percentage of phagocytic cells, neutrophil function was similar in the Control and Insulin groups at baseline (55% and 57%, respectively) and after CPB (38% and 43%, respectively). However, a quantitative determination of neutrophil phagocytic activity showed that whole blood neutrophil phagocytic capacity increased significantly in both groups at 60 min after CPB when compared with their respective baseline values and that the increase in total neutrophil phagocytic capacity was significantly more in the Insulin group compared with the Control group (P = 0.036). This observation was primarily due to a larger increase in the peripheral blood neutrophil count and not to increased activation of neutrophils. IMPLICATIONS: IV insulin, as used in this study, had effects on blood glucose only after cardiac surgery, when it was associated with an increased neutrophil count and a greater total capacity of peripheral blood neutrophils to ingest foreign particles.     

Regulation of neutrophil superoxide production in sepsis

Neutrophil superoxide production has been recognized as an important pathway for microbicidal activity and regulation of the local inflammatory environment. To investigate neutrophil superoxide production in sepsis, we studied 22 patients with intra-abdominal infections, and correlated superoxide production with chemotactic response and granular enzyme content. Our results showed that neutrophils from infected patients had specific loss of chemotactic response to C5a, and were deficient in the granular enzymes, lysozyme, and beta-glucuronidase. Superoxide production in response to opsonized zymosan was intact, but response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine was markedly depressed. This could be reversed in vitro by the addition of cytochalasin B. These results suggest that down regulation of exocytosis of superoxide to nonphagocytic stimuli occurs during sepsis, possibly protecting the host from tissue injury due to oxide radical release. Superoxide response to phagocytic stimulation was intact.     

Perioperative alteration of neutrophil functions after open heart and other major surgeries. A comparative study

The prolonged effects of cardiopulmonary bypass on neutrophil functions, as indicated by the capacity to produce superoxide and leukotrienes, were examined on the first postoperative day in ten patients who underwent open heart surgery and ten who underwent other major surgery. The superoxide and leukotriene C4 producing capacities of the neutrophils were significantly decreased postoperatively in both groups. The leukotriene B4 producing capacity, by contrast, was significantly increased postoperatively. However, there was no significant difference in values between the two groups in the pre- and postoperative periods. In both groups, neutrophil functions were significantly altered on the first postoperative day, but no specific alteration due to open heart surgery was observed.     

Increased neutrophil priming and sensitization before commencing cardiopulmonary bypass in cardiac surgical patients

BACKGROUND: Neutrophil activation is implicated in postoperative complications in patients having cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to determine the temporal fluctuations in the primability of neutrophils in the preoperative, intraoperative, and postoperative periods of CPB, and specifically whether CPB was a primary cause leading to increased neutrophil priming and elastase release. METHODS: Twenty patients undergoing multiple coronary bypass grafting, valve replacement, or both of these procedures were included in this study. Blood samples were taken 1 day before the operation and at several time points during and after the operation. For each sample, blood was divided in vitro into four subgroups: control without priming, priming alone with cytochalasin B (CytoB), priming plus stimulation with platelet-activating factor (PAF), and priming plus stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The elastase concentration of all these samples was determined using the enzyme immunoassay. RESULTS: Compared with the controls, CytoB priming increased release of elastase more than 10-fold before CPB, 1.6-fold during CPB, and 1.5-fold at the end of CPB. Further stimulation with PAF or fMLP showed greater increase of elastase than priming alone, with peak values in both found before CPB. This increased neutrophil primability prior to CPB did not differ significantly among patients who had different preoperative disease profiles. CONCLUSIONS: Our data suggest that neutrophil priming occurs early before commencing CPB in cardiac surgical patients, and that CPB is not the primary primer. Anesthesia, surgical trauma, and other events may have been involved in neutrophil priming and sensitization before CPB, which warrants further investigation.     

Sequential patterns of eicosanoid, platelet, and neutrophil interactions in the evolution of the fulminant post-traumatic adult respiratory distress syndrome.

Thirty multiply injured blunt-trauma patients at high risk for development of ARDS (multisystem trauma including more than one organ or extremity, Injury Severity Score of 26 or more, hypotension and need for 1500 mL or more blood within the first hour after admission, and PaO2 less than or equal to 70 torr) were studied sequentially with blood and physiologic evaluations beginning immediately after injury and every eight hours for eight days, or until death, to study the evolution of the ARDS process. Mixed venous blood samples were obtained for eicosanoids PGE2, PGF2 alpha, thromboxane B2, PGI2 (6-KetoPGF1 alpha) and leukotriene B4 (LTB4). Platelet (PLAT), and neutrophil (WBC) counts were also done and plasma elastase was measured. At 7:00 AM each day patient neutrophils were obtained for a study of zymosan-activated superoxide production using a chemiluminescence assay. These data were correlated with physiologic measurements of the Respiratory Index (RI), per cent pulmonary shunt (QS/QT), and respiratory compliance measures. Seven patients developed a fulminant post-traumatic ARDS syndrome within 96 hours after injury. Twelve patients without ARDS developed sepsis (TS) four or more days after injury, and 11 had uncomplicated postinjury courses (TR). Compared to both TR and TS, ARDS had a significant (p less than 0.01) rise in neutrophil superoxide production beginning on day 2 through day 4 after injury. This was preceded by rises in PGE2 and LTB4, which were significantly correlated with subsequent falls in PLAT and WBC and rises in TXB2, PGF1, and superoxide production and followed by increases in RI, QS/QT, and a fall in compliance. The significant difference in the pattern and sequence of events in ARDS compared to TR and TS patients suggests that in ARDS the earliest event may be related to peripheral release of PGE2 and LTB4 due to platelet activation and lung sequestration with release of PGF2 alpha, and by aggregation and leukocyte adherence with release of elastase. However, fulminant ARDS mortality appears to be related to the subsequent amplification of the LTB4 leukocyte activation with superoxide production that does not achieve significance before the second day after injury and rises to a maximum by day 4 after injury. These data suggest that post-trauma ARDS follows a different evolutionary pattern than that reported in animal models and is also different from that seen in human TS or TR patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neutrophil dysfunction after biomaterial contact in an in vitro model of cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) induces neutrophil degranulation and superoxide anion production in vivo. We hypothesized that CPB-associated neutrophil dysregulation alters neutrophil adhesion to vascular endothelial cells and the extracellular matrix. METHODS: We, therefore, recirculated neutrophils in polyvinyl chloride (PVC) tubing using a roller pump model and thereafter measured adhesion to cultured microvascular endothelial cells and gelatin-coated surfaces. Recirculation-induced neutrophil priming or exhaustion was tested by boosting with phorbol myristate-acetate (PMA) or N-formyl-methiolyl-leucyl-phenylalanine (FMLP) before quantification of adhesion. RESULTS AND CONCLUSION: After recirculation, neutrophils retained their adhesive capability to vascular endothelial cells, whereas adhesion to gelatin increased. This increase was not seen when the neutrophils were recirculated with a rotator instead of a roller pump, indicating that not only the pump mode but also foreign surface contact was of significance. The neutrophil PMA response after recirculation was not altered compared to resting neutrophils prestimulated with PMA. Recirculated neutrophils adhered less to cultured vascular endothelial cells after FMLP activation and more to gelatin compared to resting neutrophils prestimulated with FMLP. It is conceivable that dysregulation of neutrophil adhesive capability may play a part in the development of tissue damage after CPB.     

Effects of Hypertonic Peritoneal Dialysis Solutions on Neutrophil Superoxide Production

Superoxide produced by neutrophils plays an important role in the killing of bacterial pathogens. The effects of glucose-containing peritoneal dialysis solutions on superoxide production by canine and human neutrophils were studied. A significant decrement in superoxide generation was noted with the 2.27% and 3.86% glucose solutions. The results suggest that hypertonic peritoneal dialysis solutions curtail neutrophil superoxide generation.     

Biocompatibility of Heparin-Coated Circuits in Pediatric Cardiopulmonary Bypass

Abstract: In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), α2-plasmin plas-minogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), inter-leukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.     

In-vivo enhancement of neutrophil function by administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in cyclophosphamide (CPA) treated mice]

The in-vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and function (phagocytosis and superoxide production) of peripheral neutrophils were studied in time sequence in cyclophosphamide (CPA) treated mice. The neutrophil function was evaluated by the phagocytosis of fluorescent particles, analyzing the number of fluorescence-positive cells and the fluorescence intensity of each neutrophil by flow cytometry and also by the superoxide production, measuring chemiluminescence of the leukocyte suspension by a photometer. In CPA-treated (100 mg/kg) mice, the neutrophil function including both the phagocytosis and the superoxide production declined significantly (p less than 0.01) as the peripheral neutrophil count (PNC) decreased, reached the nadir on the same day as PNC and returned to the normal level 8 days after first CPA treated day (day 0). When rhG-CSF (100 micrograms/kg) was administered subcutaneously daily for 5 consecutive days initiating at day 1, a decrease in PNC and a decline in the neutrophil function were prevented and a significant (p less than 0.05-p less than 0.01) increase of PNC was observed after day 4. In addition, the function of increased neutrophils was significantly (p less than 0.05-p less than 0.01) enhanced after day 4 and even at day 3, when an increase in PNC was not observed yet. The study shows that rhG-CSF appears to enhance neutrophil function by a direct effect on mature neutrophils, which have been impaired by CPA at the phase of progenitor cells in the bone marrow and subsequently have appeared in the peripheral blood and that rhG-CSF is effective on the impaired host defense mechanism in CPA-treated mice, improving not only drug-induced neutropenia but also the deteriorated function of neutrophils.     

Protective effects of anti-neutrophil antibody against myocardial ischemia/reperfusion injury in rats

Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate the in vitro functions of an anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI) in rats. We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. MI was induced in Wistar rats by clamping the left coronary artery for 1 h. Rats received either isotype-negative control IgG(1) (control group, n = 20), 250 microg/kg of Urge-8 before (pre-treatment group, n = 20) or after (post-treatment group, n = 20) MI. The three groups were compared during the first 24 h after reperfusion with respect to changes in mean arterial pressure, heart rate, body temperature, biochemistry, serum cytokines, myocardial neutrophil infiltration, survival rate, and size of MI. Urge-8 effectively suppressed in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. The Urge-8 treated groups showed higher levels of arterial pressure and survival rate, lower values of interleukin-6 and interleukin-8, lower grade of myocardial neutrophil infiltration, and smaller MI size as compared to the control group. In conclusion, Urge-8 is effective against myocardial I/R injury by suppressing certain functions and myocardial infiltration of neutrophils in rats.     

Biocompatibility of heparin-coated cardiopulmonary bypass circuits in coronary patients with left ventricular dysfunction is superior to PMEA-coated circuits

BACKGROUND: Several coating techniques for extracorporeal circulation have been developed to diminish the systemic inflammatory response during cardiopulmonary bypass (CPB). The aim of this study was to evaluate the clinical effectiveness and biocompatibility of heparin-coated and poly-2-methoxyethylacrylate (PMEA)-coated CPB circuits on coronary patients with left ventricular systolic dysfunction. METHODS: Thirty-six patients who underwent elective coronary artery bypass grafting were divided into two equal groups: group H (n = 18), heparin-coated; group P (n = 18), PMEA coated. Clinical outcomes, hematologic variables, cardiac enzymes, malondialdehyde (MDA), and acute phase inflammatory response (including myeloperoxidase (MPO), catalase, hsCRP, and IL-8) were analyzed perioperatively. RESULTS: Demographic, CPB, and clinical outcome data were similar for both groups. Plasma fibrinogen, total protein, albumin, and platelet count decreased, neutrophil count, MDA, IL-8, MPO, and catalase levels increased during CPB. During CPB, MPO and catalase values were significantly higher in group P (p = 0.02 and p = 0.01) and postoperative MDA concentration was lower in group H (p = 0.03). Platelet counts were better preserved in group H during and after CPB but neutrophil count and IL-8 level did not differ between the groups. Postoperative total protein, albumin, and fibrinogen levels were higher in group H (p < 0.05). The postoperative first day levels of troponin-I, CK-MB, and CRP increased in both groups without any significant differences between the groups. CONCLUSIONS: Heparin-coated circuit provided better suppression of perioperative inflammatory markers and exhibited more favorable effects on hematologic variables than PMEA-coated circuit.     

Effects and arterial concentration of prostaglandin E1 during cardiopulmonary bypass

The effects an infusion prostaglandin E1 (PGE1) on both haemodynamics and PGE1 arterial blood concentration during and after cardiopulmonary bypass (CPB) were studied in 15 patients (eight patients received PGE1 30 ng kg-1 min-1; seven served as controls and did not receive PGE1 administration). Mean arterial blood pressure and systemic vascular resistance were significantly lower in the PGE1 group than in the control group during CPB. There were no statistically significant differences between the two groups with regard to mean pulmonary-artery pressure, central venous pressure, and cardiac or perfusion index. The arterial blood concentration of PGE1 in the control group during CPB was about 50 pg ml-1. In the PGE1 group it increased rapidly after the beginning of CPB and reached a level of 1500 pg ml-1 at 60 min of CPB. After weaning off CPB, PGE1 concentration decreased rapidly to 70 pg ml-1 in spite of the continuous PGE1 infusion. It is concluded that the metabolism of PGE1 is strongly inhibited during CPB and the effects of PGE1 may be unexpectedly heightened. Therefore, the infusion rate of PGE1 during CPB should be 30 ng kg-1 min-1 or less in order to avoid severe hypotension.     

Effects of phospholipase D on cardiopulmonary bypassinduced neutrophil priming

To investigate the relationship betweenphospholipase D (PLD) activation and neutrophil priminginduced by cardiopulmonary bypass (CPB), and try toclarify whether CPB-induced systemic inflammatoryresponse can be attenuated by inhibiting neutrophilic PLDactivation.     

Acceleration of superoxide production from leukocytes in trauma patients.

Superoxide (O2-) and granulocyte elastase (GE) from neutrophils mediate host defense and tissue injury in inflammation. To determine alterations in leukocyte function after trauma, O2- production and GE secretion from neutrophils were studied in trauma patients (n = 20) and healthy controls (n = 15). The priming effect of tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha), and lipopolysaccharide (LPS) on O2- or GE release also was evaluated. Superoxide production (nmole/10 minutes) was elevated significantly in trauma patients at days 0 (9.5 +/- 4.8), 1 (14.2 +/- 7.3), and 3 (12.2 +/- 5.9) and returned to control levels (4.2 +/- 1.6) by day 7. There was no difference in GE secretion between trauma patients and healthy controls. Incubation of neutrophils with TNF induced release of both O2- and GE. Superoxide production was induced by TNF at concentrations at or greater than 10(-11) mol/L. Granulocyte elastase secretion was induced in a time- and dose-dependent manner by TNF at concentrations between 10(-10) and 10(-7) mol/L. In contrast IL-1 alpha and LPS did not potentiate O2- or GE release. These results suggest that neutrophil O2- production increases acutely in trauma. Tumor necrosis factor may mediate this O2- and GE production by neutrophils involved in the inflammatory response.     

戊乙奎醚对心肺转流中患者血浆sTM和vWF水平的影响

目的研究戊乙奎醚(长托宁)对心肺转流(CPB)全身性血管内皮细胞(VEC)急性损伤的保护作用。方法30例择期瓣膜置换手术患者随机分为两组,每组15例。观察组术前肌注戊乙奎醚0.02mg/kg和吗啡0.01mg/kg;东莨菪碱组术前肌注东莨菪碱0.3mg和吗啡0.01mg/kg。分别于术前、CPB前、CPB后30min、停CPB、手术结束、术后1d和3d采血测血浆可溶性血栓调节蛋白(sTM)和血管性假血友病因子(vWF)的变化。结果两组血浆sTM和vWF在CPB后30min至术后1d均显著增高(P<0.01),术后3d恢复到术前水平。观察组患者CPB期间至术后3d的所有指标均低于对照组。结论CPB可导致全身性VEC急性损伤,戊乙奎醚可以显著减轻CPB导致的VEC损伤。