The effect of body temperature on leukocyte kinetics during cardiopulmonary bypass

Leukocyte kinetics were investigated in 22 patients undergoing cardiopulmonary bypass to determine the nature of the changes in the white blood cell count associated with this procedure. Both polymorphonuclear leukocytes and lymphocytes were taken up by the lung as pulmonary blood flow was lowered, but only polymorphonuclear leukocytes were taken up as blood flow was restored. The complement 3a level was increased approximately twice the control value within 2 minutes of going on bypass and remained elevated throughout the procedure. The peripheral white blood cell count doubled during the bypass procedure owing to a release of polymorphonuclear leukocytes and their precursors from the bone marrow. The increase in polymorphonuclear leukocytes was prevented by hyperthermia but reappeared quickly when the body temperature was restored to 36 degrees to 37 degrees C.     

Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans.

To assess leukocyte activation during cardiopulmonary bypass, we measured white blood cell and neutrophil counts and lysosomal enzyme release, especially myeloperoxidase and elastase, throughout the operation and for 5 days postoperatively. A newly developed double antibody radioimmunoassay of myeloperoxidase and an enzyme-linked immunosorbent assay for detection of the polymorphonuclear elastase-alpha 1-proteinase inhibitor complex were used to determine their plasma levels in 15 patients undergoing elective aorta-coronary bypass grafting. Preoperatively white blood cell counts and plasmatic levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor were normal. Because no correlation has yet been established between levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor, the aim of this prospective study was to evaluate the use of these enzyme levels as markers for leukocyte activation in vivo. We addressed the clinical situation of cardiopulmonary bypass because it offered the possibility of monitoring the comparative evolution of blood levels of these enzymes in parallel to white blood cell counts through well-defined steps corresponding to known events. We document the advantages of myeloperoxidase blood levels over elastase measurement as reflecting more rapidly the in vivo activation of leukocytes. The time course kinetics of these three measurements were not parallel. White blood cell counts remained stable at the beginning of bypass, whereas myeloperoxidase levels increased sharply and continuously as soon as bypass was instituted until the end of bypass. Elastase levels also increased, but later than myeloperoxidase, beginning when the patients was rewarmed. High elastase plasma levels persisted later than myeloperoxidase after bypass, in parallel with white blood cell counts. It thus clearly appears that changes in myeloperoxidase levels more rapidly reflect the activation state of leukocytes induced by cardiopulmonary bypass and surgery, whereas peak levels of elastase were delayed and parallel to white blood cell counts. From this model, in which the evolution of leukocyte numbers could be followed in relation with known steps of stimulation, it appears that myeloperoxidase is a sensitive marker for monitoring in vivo activation of white blood cells.     

Efficacy of haemofiltration during cardiopulmonary bypass in paediatric open heart surgery

Purpose Haemofiltration is a useful method for removing fluid overload in paediatric patients undergoing open heart surgery. However, its role in reducing the inflammatory response to cardiopulmonary bypass (CPB) is still controversial. This study was undertaken to examine the efficacy of haemofilter in reducing the inflammatory response to CPB in paediatric patients undergoing open heart surgery. Methods We studied 20 paediatric patients undergoing open heart surgery with long duration CPB. In ten patients conventional methods of suppressing inflammation, like aprotinin and methylprednisolone were used and in the other ten patients, haemofiltration was added to the conventional methods. Inflammatory response was assessed by increase in total white blood cell counts and decrease in complement factor 3 (C3) levels. Patients were followed up in the intensive care unit. Result The fall in C3 concentration and increase in WBC counts was significantly more in conventional group (29.1% and 81% respectively) as compared to the haemofilter group (11.4% and 37% respectively). However, it did not reflect on any significant increase in postoperative PaO2, decrease in mechanical ventilation or ICU stay. Conclusion Use of haemofilter decreases the inflammatory response, but its clinical implication in postoperative period is still not clear.     

Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man

We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10(-7) mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F1 alpha, the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 +/- 0.3 versus 3.7 +/- 0.2 nmol/10(6) polymorphonuclear neutrophils per minute, p less than 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 +/- 2.5 nmol/10(6)/min in control patients and 7.1 +/- 0.9 nmol/10(6)/min in those receiving deferoxamine (p less than 0.05). In contrast, plasma levels of 6-keto-prostaglandin F1 alpha were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less "primed" by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.     

A prospective, randomized study of the effects of prostacyclin on platelets and blood loss during coronary bypass operations

A randomized, double-blind study was designed to evaluate the therapeutic effect and safety of prostacyclin (epoprostenol) in patients undergoing cardiopulmonary bypass. One hundred patients having isolated coronary bypass grafting received 300 units/kg of heparin and then either prostacyclin (12.5 ng/kg/min from heparinization until cardiopulmonary bypass, 25 ng/kg/min during bypass) or buffer/diluent in a similar manner. Standardized anesthetic, perfusion, and surgical techniques were used. Drug and placebo groups were similar in demographic data and bypass times, and there were no deaths. Activated coagulation time and platelet count were significantly higher during cardiopulmonary bypass in patients receiving prostacyclin. Platelet count remained significantly higher 24 hours after bypass in the active drug group. Immediately after operation, there was significantly less prolongation of bleeding time (1.3 versus 2.9 minutes; p = 0.009) in the patients receiving prostacyclin. Blood loss was significantly reduced during the first 4 hours postoperatively in the prostacyclin group (261 +/- 159 versus 347 +/- 197 ml; p = 0.02). There was no significant difference between the groups when total blood loss was compared (710 +/- 351 versus 869 +/- 498 ml; p = 0.07). Patients receiving prostacyclin required an average of 257 ml less blood transfused in the intensive care unit (p = 0.02). We conclude that the clinical impact of prostacyclin in patients undergoing coronary artery operations was demonstrable, but small. Prostacyclin may provide clinical benefits in patients undergoing cardiopulmonary bypass when there are contraindications to or other difficulties with blood transfusion. With prostacyclin, reduced heparin dose is possible and therefore reduced protamine requirement would offer a potential benefit of less cardiovascular depression immediately after bypass. However, the advantages offered by prostacyclin are not sufficient to recommend its routine use during cardiopulmonary bypass.     

Complement activation and lung permeability during cardiopulmonary bypass

Pulmonary dysfunction after cardiopulmonary bypass has been attributed to the damaging effects of complement activation on the lung. To further explore this phenomenon, we measured plasma levels of activated complement components (radioimmunoassay), assessed neutrophil n-formyl-methionyl-leucyl-phenylalanine (FMLP) receptor status (radioligand saturation binding assay), and quantified pulmonary epithelial permeability as radioaerosol lung clearance of technetium 99m-labeled diethylenetriamine pentaacetic acid in a series of 8 patients undergoing cardiopulmonary bypass. Significant elevations of plasma C3adesArg, C4adesArg, and C5adesArg levels were seen just after CPB, indicating activation of both the classic and alternate complement pathways. Neutrophil activation was evident as increased expression of neutrophil FMLP surface receptors after bypass. Despite the presence of complement and neutrophil activation, increased pulmonary epithelial permeability was not seen. These data support the hypothesis that complement and neutrophil activation during cardiopulmonary bypass is not associated with acute lung injury, at least not pulmonary epithelial injury. One can therefore infer that increased pulmonary epithelial permeability in patients at high risk for and experiencing sepsis-induced and trauma-induced adult respiratory distress syndrome may be due to factors other than complement and neutrophil activation.     

Biocompatibility of extracorporeal circulation with autooxygenation.

Platelet damage, complement activation and neutropenia during cardiopulmonary bypass are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate biocompatibility of this kind of bypass we compared two techniques of extracorporeal circulation in 40 patients undergoing elective coronary bypass operations. In 20, a standard technique with a bubble oxygenator was used (group 1), and in the remaining 20 patients with autooxygenation, the patients' own lungs were included in the perfusion circuit (group 2). Several blood samples were taken before, during and after perfusion to estimate the corrected platelet numbers and pulmonary leucocyte sequestration in all patients, and additionally in 6 patients from each group, complement C3a and C5a anaphylatoxins were measured (radioimmunoassay). At the end of cardiopulmonary bypass, the decline of platelet number corrected to haematocrit platelet number in group 1 was significantly higher than in group 2 (P less than 0.01). There was a significant increase in circulating white blood cells when compared to pre-bypass time in both groups (P less than 0.05). However, comparison of differences between leucocyte counts in the blood of the patients' right and left atria showed enhanced leucocyte sequestration in group 1, 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group 2. The C3a rose progressively during extracorporeal circulation: in group 1 from 268 +/- 46 ng/l to 521 +/- 65 ng/l, and in group 2 from 244 +/- 46 ng/l to 418 +/- 34 ng/l (P less than 0.05). No characteristic changes in C5a activation were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of operations with cardiopulmonary bypass on polymorphonuclear leukocyte function in infants

To determine the effect of operations with cardiopulmonary bypass on the immunologic function of polymorphonuclear leukocytes in infants, we studied polymorphonuclear leukocyte function and immunologic profile in 16 infants undergoing repair of congenital heart lesions. An oxygen/air/high-dose fentanyl anesthetic was used for all patients. Absolute neutrophil count increased significantly (p less than 0.05) after bypass and remained increased 48 hours afterward. Chemotaxis, random migration of polymorphonuclear leukocytes, and phagocytic index were unaffected, but bactericidal capacity decreased significantly immediately after cardiopulmonary bypass and remained decreased 48 hours later. Serum opsonizing capacity to bacterial and fungal antigens was variably altered, and complement factors 3 and 4 decreased significantly after cardiopulmonary bypass. Total hemolytic complement decreased significantly immediately after cardiopulmonary bypass and returned to normal by 48 hours. These data suggest that operations with cardiopulmonary bypass in infants significantly affect the immunologic function of polymorphonuclear leukocytes and result in consumption of complement.     

Complement (C3, C4) Consumption in Cardiopulmonary Bypass,Cardioplegia, and Protamine Administration

Anaphylatoxins produced by complement activation have been postulated to be responsible for postperfusion syndrome and protamine hypotension in patients undergoing cardiac surgical procedures. The consumption of serum complement components C3 and C4, which reflects the classic and alternate pathway activations of the complement system, was studied in 22 patients undergoing cardiac operations. Prior to the onset of cardiopulmonary bypass, the complement levels were within normal range. Rapid reduction in both C3 and C4 within minutes of cardiopulmonary bypass indicated rapid complement activation. Such a reduction in complement levels could not be accounted for by either hemodilution or transfusion of complement-poor blood. Aortic cross-clamping and cold potassium cardioplegia followed by myocardial reperfusion did not lead to further consumption of C3 and C4. Slow intravenous infusion of protamine sulfate after cardiopulmonary bypass did not change C3 and C4 levels significantly in our patients, although protamine and heparin-protamine complex have been shown to activate complement components in vitro.In another group of 9 similar cardiac surgical patients, C3 and C4 were found to return to normal levels within 24 hours after operation. This study thus confirms the rapid activation of the complement system by cardiopulmonary bypass but fails to demonstrate further activation of the complement system by cardioplegia or protamine administration.     

Activation of complement and leukocyte receptors during on- and off pump coronary artery bypass surgery.

OBJECTIVE: The aim of this prospective, randomised study was to investigate the influence of extracorporeal circulation on the inflammatory response, our hypothesis being that off pump coronary artery bypass grafting (OFFCAB) procedures would generate less activation than on pump procedures (ONCAB). METHODS: Patients admitted for elective CABG were randomised to either ONCAB or OFFCAB surgery and blood samples were taken during and up to 24 h after the operation. We measured complement factors C5a and the terminal complement complex (TCC, C59-b), and the interleukins IL-6 and IL-8. Leukocytes were studied for cellular counts and adhesion molecules (CD11b, CD35 and CD62L) by flow cytometry. We included a combination of activity markers with different aspects of neutrophil function and combined these with in vitro activation. RESULTS: The complement factors C5a and TCC showed a more rapid (P=0.02, P<0.001) and TCC a more profound (P<0.001) increase in the ONCAB group than in the OFFCAB group during the operation, after that there were no inter-group differences. Cellular markers, cell counts and interleukin levels were activated by surgery but with no difference between groups. CONCLUSION: This prospective, randomised study showed less complement activation in low risk OFFCAB, compared to ONCAB patients.     

Postischemia Myocardial Injury in Coronary Artery Bypass Patients (PP6)

Purpose

To investigate the reperfusion injury of the myocardium in patients undergoing elective coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB), we monitored the blood levels of troponin I (TNI), white blood cells, oxygen radicals, malondialdehyde, and myeloperoxidase seeking to define the relationship between the CABG-induced systemic inflammation and myocardial injury.

Materials and methods

We selected 10 patients undergoing primary CABG with CPB at moderate hypothermia and cardioplegic arrest concomitant with intermittent warm blood cardioplegia. We compared all data with their own baseline values to study the reperfusion injury. After release of the aortic clamp, blood was drawn from the coronary sinus, via a catheter placed through the right atrium. We measured plasma levels of inflammatory mediators, such as malondialdehyde, myeloperoxidase, oxygen radicals, and the myocardium injury parameter of TNI.

Results

Patients showed no difference concerning aortic clamp time. TNI increased significantly at 1, 15, and 30 minutes after the onset of reperfusion. Blood levels of white blood cells, oxygen radicals, malondialdehyde, and myeloperoxidase also increased significantly with reperfusion time.

Conclusions

Reperfusion of ischemic myocardium induced increased TNI, which may be related to the systemic inflammatory responses induced by ischemia and reperfusion of the myocardium among patients undergoing elective coronary bypass surgery.     

Plasma levels of main granulocyte components during cardiopulmonary bypass

Plasma levels of granulocyte lactoferrin, myeloperoxidase, and elastase in alpha 1-proteinase inhibitor complex were compared with C3a and C5a levels in 10 patients undergoing cardiopulmonary bypass. At the end of the operation, plasma levels of lactoferrin increased from 97.0 +/- 22.8 to 1257 +/- 139.8 ng/ml, myeloperoxidase increased from 37.1 +/- 4.3 to 170.9 +/- 34.9 ng/ml, and elastase in alpha-proteinase inhibitor complex rose from 89.4 +/- 7.4 to 437.8 +/- 97.3 ng/ml. There was also a significant anaphylatoxin formation. To investigate the relationship between complement and granulocyte activation, patients undergoing cardiopulmonary bypass received the calcium channel blocker nifedipine (orally and intravenously) and the antiplatelet drug dipyridamole. The continuous infusion of nifedipine (5.91 +/- 0.53 micrograms/kg body weight per hour) caused significantly lower levels of elastase in alpha-proteinase inhibitor complex and lactoferrin but not anaphylatoxin. Dipyridamole was without effect on complement and granulocyte activation during cardiopulmonary bypass. Our data demonstrate inhibition of granulocyte activation during cardiopulmonary bypass by continuous infusion of nifedipine, even in the presence of complement activation.     

Variations in blood platelet-activating-factor levels after protamine reversal of heparin in humans

The potent inflammatory mediator PAF-acether (PAF = platelet-activating factor) can produce the same hemodynamic and hematological effects as protamine infusion. In 10 patients, blood PAF and precursor levels were measured in the left atrium, the pulmonary and the radial artery before and after protamine reversal of heparin during coronary artery bypass graft. Blood PAF level in the left atrium increased 6-fold (17 +/- 12 pg.ml-1 vs 98 +/- 46 pg.ml-1, P = 0.03) after protamine infusion. By contrast, a 4-fold decrease was observed in the pulmonary artery blood (130 +/- 48 pg.ml-1 vs 31 +/- 23 pg.ml-1, P = 0.03) and a 9-fold decrease was noted in the radial artery blood (285 +/- 104 pg.ml-1 vs 31 +/- 15 pg.ml-1, P = 0.01). No cardiovascular impairment was observed but all patients exhibited thrombocytopenia. After protamine, PAF in the left atrium reached lower levels than those observed in the pulmonary and radial artery before protamine infusion. Moreover, no significant correlation was observed between platelet counts and PAF levels. Thus PAF seems not to mediate the platelet drop induced by heparin-protamine complexes. A positive correlation was obtained between leukocyte counts in the pulmonary artery and PAF levels in the left atrium (r = 0.78, P = 0.02). Protamine infusion may stimulate PAF biosynthesis by leukocytes in the lung, on the one hand, and accelerate the disappearance of PAF in the arterial bed, on the other hand.     

A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation

This randomized, double-blind study was designed to evaluate the effect of prostacyclin (epoprostenol) on the incidence and severity of postoperative neuropsychologic dysfunction in patients undergoing coronary artery operation. Four days before operation and 1 week after operation, 100 patients having coronary artery bypass grafting underwent detailed neurologic and psychologic examinations and computed tomographic scans of the brain. The psychologic examination was repeated 2 months after operation. During cardiopulmonary bypass, all patients received 300 U/kg of heparin and then either buffer-diluent or prostacyclin (12.5 ng/kg/min from the time of heparinization until onset of cardiopulmonary bypass and 25 ng/kg/min during cardiopulmonary bypass). No deaths or major neurologic complications occurred in this series. Ninety-six patients completed the psychologic and neurologic evaluations 1 week after operation; 74 of these patients were evaluated psychologically 2 months after operation. Psychologic testing demonstrated similar declines in postoperative performance in both the prostacyclin-treated and the control groups; these changes were no longer present in either group 2 months after operation. Results of neurologic examinations and computed tomographic scans of the brain were unchanged. We conclude that the administration of prostacyclin during cardiopulmonary bypass in patients undergoing routine coronary artery operation has no effect on perioperative cognitive changes.     

Hemodynamic effects of methylprednisolone in patients undergoing cardiac operation and early extubation.

BACKGROUND: Whether or not methylprednisolone is beneficial during cardiac operation remains controversial. This study examines the effects of the drug on complement activation and hemodynamics in patients undergoing cardiac operation and early extubation. METHODS: Patients undergoing cardiac operation were randomized to receive either intravenous methylprednisolone (group MP) or intravenous placebo (group NS). Complement 3a (C3a) levels and hemodynamic parameters were obtained perioperatively. Extubation was accomplished at the earliest clinically appropriate time. RESULTS: Both groups exhibited equivalent increases in C3a levels after exposure to bypass. Group MP exhibited increased cardiac index, decreased systemic vascular resistance, and increased shunt flow when compared to group NS. More group MP patients required hemodynamic support and group MP patients had prolonged extubation times. CONCLUSIONS: Methylprednisolone was unable to attenuate complement activation and led to hemodynamic alterations (primarily vasodilation) that may hinder early extubation in patients after cardiac operations.     

Fibrinolysis and complement-system profiles during aorto-femoral bypass implantation

In 51 patients undergoing either implantation of an aortofemoral bypass (38 patients) or of an saphenous bypass (13 patients) the fibrinolytic and complement system profiles were determined. During the course of an aortofemoral bypass the plasminogen concentration decreased by 40%, alpha 2-macroglobulin by 25%, the complement factor C3c by 20% and the complement factor C4 by 40%. Antithrombin III concentration remained stable until the third postoperative day. The alpha 1-antitrypsin concentration increased postoperatively by 40% compared to the preoperative control. The concentrations of plasminogen, antithrombin III, alpha 2-macroglobulin and complement factor C4 did not change in the patients undergoing saphenous bypass operation. Intraoperatively the complement factor C3c decreased by 20%, while alpha 1-antitrypsin showed postoperatively an increase by 30%. Anaesthesia (neuroleptanaesthesia, halothane- or continuous thoracal epidural anaesthesia) had no influence on the fibrinolytic and complement system profiles. Neither could a correlation be shown between the intraoperative haemodynamic changes and the concentrations of the factors of the fibrinolytic and complement system.     

Reduction of pro-inflammatory cytokine levels and cellular adhesion in CABG procedures with separated pulmonary and systemic extracorporeal circulation without an oxygenator

Objective: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. Methods: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. Results: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44±15% and +43±28% of the respective right atrial values. The respective values in bilateral circulation were −3±4% and −6±7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet–monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (−21±6%), but washed out in bilateral circulation (+5±8%, P=0.007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (−16±9%) but washed out in bilateral circulation (+19±29%, P=0.05; all data given as mean±SEM). Conclusions: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.     

Ventilation during Cardiopulmonary Bypass: Impact on Neutrophil Activation and Pulmonary Sequestration

Background: Cardiopulmonary bypass (CPB) is associated with neutrophil activation, pulmonary sequestration, and release of inflammatory mediators leading to pulmonary dysfunction. We investigate the effect of continuous ventilation during cardiopulmonary bypass on neutrophil activation and pulmonary sequestration. Methods: Forty-six patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively randomized to continuous ventilation and nonventilation groups. Blood samples were collected, and bronchoalveolar lavage (BAL) was performed following induction of anesthesia and at 4 hr after aortic declamping. Differential white cell count was measured, and flow cytometry to determine cell count numbers and quantify CD45 and CD11b leukocyte cell surface adhesion molecule expression was performed on the blood and BAL samples. Results: Twenty-three patients were randomized to standard nonventilated CPB and 23 patients to ventilation throughout CPB. Significant increases in blood and BAL neutrophil numbers were detected at 4 hr following aortic declamping in both groups (Blood: NV p <. 0001, V p <. 0001; BAL: NV p =. 017, V p =. 0007). No significant inter-group differences in BAL and blood neutrophil numbers were found. Significantly higher blood neutrophil CD11b mean fluorescent intensity levels were present 4 hr following declamping compared with baseline in both groups (NV Blood, p =. 021; V Blood p <. 0001). No significant inter- or intragroup differences in BAL neutrophil CD11b mean fluorescent intensity levels were found. There was no death or major complication. Conclusions: Cardiopulmonary bypass during coronary artery bypass grafting is associated with increased neutrophil pulmonary sequestration, and blood neutrophil CD11b activation. Continuous ventilation during cardiopulmonary bypass does not significantly reduce neutrophil pulmonary sequestration or activation.     

Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.     

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function

BACKGROUND: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. METHODS: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the PaO2/FIO2 ratio. RESULTS: Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. CONCLUSIONS: Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively (p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bondingtf the circuits has minor effects on the pattern of evolution of this inflammatory response.