Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators

A prospective randomized trial involving 91 patients undergoing cardiopulmonary bypass compared the effects of bubble oxygenators (with and without methylprednisolone sodium succinate) and membrane oxygenators on complement activation and transpulmonary sequestration of leukocytes. Patients were divided as follows: Group I, 30 patients, bubble oxygenator; Group II, 31 patients, bubble oxygenator and methylprednisolone sodium succinate (30 mg/kg); Group III, 30 patients, membrane oxygenator. In Group I, C3a increased from 323 +/- 171 ng/ml during cardiopulmonary bypass to 1,564 +/- 785 ng/ml at 25 minutes after bypass (p less than 0.0001). A significant decrease in C3a was found in Groups II and III compared to Group I (p less than 0.0001). C5a did not change significantly during cardiopulmonary bypass in any group. Reestablishment of pulmonary circulation at the end of bypass produced significant transpulmonary leukocyte sequestration in Group I; the median cell difference was 1,700/microliter. Transpulmonary sequestration was significantly (p less than 0.0001) less in Group II (median cell difference = 200/microliter) and in Group III (median cell difference = 400/microliter) than in Group I. We conclude that cardiopulmonary bypass with a bubble oxygenator alone initiates significantly (p less than 0.0001) more C3a activation and leukocyte sequestration than when methylprednisolone sodium succinate (30 mg/kg) is given 20 minutes before the start of cardiopulmonary bypass with a bubble oxygenator or when a silicone membrane oxygenator is used.     

Evidence for complement activation by protamine-heparin interaction after cardiopulmonary bypass

Complement activation by the alternate pathway has been implicated in the pathophysiology of cardiopulmonary bypass (CPB), and laboratory studies suggest that the complement cascade may be activated by the protamine-heparin complex. To determine if the administration of protamine to patients receiving heparin activates complement, we studied 100 patients undergoing CPB by assaying levels of C3a and C4a (classic pathway) at regular intervals before and after protamine administration. In group I (90 patients), protamine was given at the usual interval (median 5 minutes) after CPB. In group II (10 patients), protamine was withheld until skin closure (median 45 minutes) after CPB. Results demonstrated that C4a was not activated during CPB in either group. After CPB, the C4a level in group I was 459 ng/dl and increased to 1047 ng/dl 10 minutes after protamine administration (p less than 0.001). In group II, the C4a level was 484 ng/dl at the end of CPB and 354 ng/dl 15 minutes later, which corresponds to the value immediately after protamine administration in group I. The delayed administration of protamine in group II caused a significant increase in C4a at the time of skin closure (1090 ng/dl; p less than 0.001). Corresponding results from C3a analysis before and after protamine administration confirmed the activation of complement cascade. Our study provides the first clinical evidence that the protamine-heparin complex activates complement via the classic (C4a) pathway. The hemodynamic effects of protamine after CPB may be related to complement activation.     

The factors effecting complement activation in open heart surgery.

The activation of the complement system was investigated in 10 patients with rheumatic valve disease having heart surgery. The C3c, C4, leukocyte count and polymorphonuclear neutrophil count were determined in the blood samples taken before anaesthesia, after anaesthesia, 10 minutes after protamine administration and after the closure of the skin incision. In addition, atrial blood samples were taken after the release of the cross-clamp and pulmonary neutrophil trapping was investigated. In this study C3c and C4 consumption was found to take place after 30 minutes of CPB (cardiopulmonary bypass) and 10 minutes after protamine administration; the affects of anaesthesia and heparin were not significant.     

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.     

Coagulation defects in neonates during cardiopulmonary bypass.

We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits.     

The effects of cardiopulmonary bypass temperature on inflammatory response following cardiopulmonary bypass.

OBJECTIVES: The inflammatory response to cardiopulmonary bypass is believed to play an important role in end organ dysfunction after open heart surgery and may be more profound after normothermic systemic perfusion. The aim of the present study was to investigate the effects of cardiopulmonary bypass temperature on the production of markers of inflammatory activity after coronary artery surgery. METHODS: Forty-five low risk patients undergoing elective coronary artery surgery were prospectively randomized into three groups: hypothermia (28 degrees C, n = 15), moderate hypothermia (32 degrees C, n = 15), and normothermia (37 degrees C, n = 15). All patients received cold antegrade crystalloid cardioplegia and topical myocardial cooling with saline at 4 degrees C. Serum samples were collected for the estimation of neutrophil elastase, interleukin 8, C3d, and IgG under ice preoperatively, 5 min after heparinisation, 30 min following start of CPB, at the end of CPB, 5 min after protamine administration, and 4, 12 and 24 h postoperatively. RESULTS: Patients were similar with regard to preoperative and intraoperative characteristics (age, sex, severity of symptoms, number of grafts performed, aortic cross clamp time, cardiopulmonary bypass time). Neutrophil elastase concentration increased markedly as early as 30 min after the onset of cardiopulmonary bypass and peaked 5 min after protamine administration. Levels were not significantly different between the three groups. A similar finding was apparent for C3d release. Interleukin 8 concentrations also demonstrated a considerable increase related to cardiopulmonary bypass in all groups, but there was a significantly more rapid decline in interleukin 8 concentrations in the normothermic group in the postoperative period. Eluted IgG fraction showed a much earlier peak concentration than the other markers, occurring within 30 min of the start of cardiopulmonary bypass. Levels reached a plateau, before declining soon after the end of bypass and remained higher than preoperative values at 24 h. There was no difference between the three groups. The cumulative release of all markers was calculated from the concentration-time curves, and was not statistically different between groups. CONCLUSION: Normothermic systemic perfusion was not shown to produce a more profound inflammatory response compared to hypothermic and moderately hypothermic cardiopulmonary bypass.     

Pulmonary hypertension after heparin-protamine: roles of left-sided infusion, histamine, and platelet-activating factor

Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet-activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin.     

Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important

INTRODUCTION: Cardiopulmonary bypass produces an inflammatory response that can cause significant postoperative pulmonary dysfunction and total body edema. This study evaluates the efficacy of preoperative methylprednisolone administration in limiting this injury in neonates and compares the effect of giving methylprednisolone 8 hours before an operation to the common practice of adding methylprednisolone to the cardiopulmonary bypass circuit prime. METHODS: A control group of neonatal pigs (control; n = 6) received no preoperative medication. One experimental group (n = 6) received methylprednisolone sodium succinate (30 mg/kg) both 8 and 1.5 hours before the operation. A second experimental group received no preoperative treatment, but methylprednisolone (30 mg/kg) was added to the cardiopulmonary bypass circuit prime. All animals underwent cardiopulmonary bypass and 45 minutes of deep hypothermic circulatory arrest. Hemodynamic and pulmonary function data were acquired before cardiopulmonary bypass and at 30 and 60 minutes after bypass. RESULTS: In the control group, pulmonary compliance, alveolar-arterial gradient, and pulmonary vascular resistance were significantly impaired after bypass (P <.01 for each by analysis of variance). In the group that received methylprednisolone, compliance (P =.02), alveolar-arterial gradient (P =.0003), pulmonary vascular resistance (P =.007), and extracellular fluid accumulation (P =.003) were significantly better after bypass when compared with the control group. Results for the group that received no preoperative treatment fell between the control group and the group that received methylprednisolone. CONCLUSIONS: When given 8 hours and immediately before the operation, methylprednisolone improves pulmonary compliance after bypass, alveolar-arterial gradient, and pulmonary vascular resistance compared with no treatment. The addition of methylprednisolone to the cardiopulmonary bypass circuit prime is beneficial but inferior to preoperative administration.     

A comparison of washed red blood cells versus packed red blood cells (AS-1) for cardiopulmonary bypass prime and their effects on blood glucose concentration in children

The effects on blood glucose concentrations of packed red blood cells (AS-1) (group I) versus washed red blood cells (group II) for cardiopulmonary bypass prime were compared in 20 infants weighing less than 10 kg undergoing cardiac surgical procedures. All patients were anesthetized with N2O/O2/isoflurane/fentanyl and received lactated Ringer's solution prior to bypass. Blood glucose concentrations prior to bypass were 85 +/- 15 mg/dl (mean +/- SD) in group I and 81 +/- 14 mg/dl in group II. Blood glucose concentrations were 210 +/- 21 mg/dl versus 78 +/- 14 mg/dl (P less than 0.001) 10 min after initiation of bypass, 241 +/- 48 mg/dl versus 107 +/- 28 mg/dl (P less than 0.001) prior to separation from bypass, and 214 +/- 52 mg/dl versus 97 +/- 19 mg/dl (P less than 0.001) after protamine administration in group I and group II, respectively. The use of washed red blood cells for cardiopulmonary bypass priming solution in infants significantly attenuates the increase in blood glucose concentration otherwise observed during cardiopulmonary bypass.     

Comparison of two protocols for heparin neutralization by protamine after cardiopulmonary bypass

Twenty patients undergoing cardiac operations were randomly assigned to two protocols for heparin neutralization by protamine after cardiopulmonary bypass. In all patients protamine chloride was given at a ratio of 1 unit of protamine to 1 unit of injected heparin. In Group I (10 patients) all protamine was infused within 10 minutes after termination of cardiopulmonary bypass. Group II (10 patients) received 75% of the calculated protamine dose within 10 minutes after termination of bypass and the remainder after transfusion of all blood in the heart-lung machine. Plasma heparin levels were significantly lower in Group II 5 minutes after transfusion of all blood in the heart-lung machine and were 0.13 units/ml (standard deviation 0.04) in Group I and 0.06 units/ml (standard deviation 0.05) in Group II (p less than 0.001) 60 minutes after bypass. Activated partial thromboplastin time mirrored the changes in plasma heparin, whereas activated clotting time (Hemochron) was too insensitive to detect these low plasma heparin levels. We conclude that the two-dose protocol resulted in more complete heparin neutralization than the one-dose protocol.     

In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: arterial in-line application in a porcine cardiac surgery model

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass is associated with aberrant neutrophil activation and potentially severe pathogenic sequelae. This experimental study was done to evaluate a leukocyte inhibition module that rapidly inactivates neutrophils through CD95 stimulation. METHODS: German landrace pigs (4 groups, each n = 5) underwent cardiac surgery without cardiopulmonary bypass (group I), with cardiopulmonary bypass (group II), with cardiopulmonary bypass plus a leukocyte filter (group III), and with cardiopulmonary bypass plus a leukocyte inhibition module (group IV). The leukocyte filter or leukocyte inhibition module was introduced into the arterial line of the heart-lung machine. RESULTS: Leukocyte counts were decreased by up to 43% in group IV compared with values in group II (P =.023). In group IV, but not in groups I to III, no delay in spontaneous neutrophil apoptosis was observed after annexin V-propidium iodide staining. Late apoptotic (11.7%) or necrotic neutrophils (9.3%) were detected in 2 animals (group IV). Tumor necrosis factor alpha serum levels increased over time in groups I to III (>2-fold) but remained at baseline levels in group IV (P <.05). Interleukin 8-mediated chemotactic neutrophil transmigration activity increased over time in groups I to III but was totally abrogated in group IV at any time point. The perioperative increase of creatine kinase and creatine kinase MB levels was lower in groups III (1.5-fold and 1.3-fold, respectively) and IV (1.2-fold and 1.5-fold, respectively) compared with values in group II (both 1.9-fold). CONCLUSIONS: The leukocyte inhibition module downregulated cardiopulmonary bypass-related neutrophil activity and thus might be beneficial in cardiac surgery and other clinical settings with unappreciated neutrophil activation.     

Role of paf-acether in protamine-induced thrombocytopenia in rabbits.

The effects of protamine (6 mg kg-1) injected after heparin (5 mg kg-1) have been studied in five groups of five New Zealand white rabbits. Group I was treated with the sequence heparin-protamine and group II with protamine alone. The animals of groups III and IV received respectively intravenous indomethacin (3 mg kg-1) and BN 52021 (3 mg kg-1), a paf receptor antagonist before the sequence heparin-protamine. Group V was pre-treated with indomethacin and BN 52021 before heparin reversal with protamine. In group I, immediate thrombocytopenia (44.1 +/- 4.6% of baseline level, P less than 0.05) and leucopenia (55.5 +/- 2.3% of baseline level, P less than 0.05) were observed 30 s after protamine reversal of heparin, paralleled with an increase in blood paf levels (27.6 +/- 27.6 vs. 148.2 +/- 48.9 pg ml-1, P less than 0.05). In group II, protamine alone induced no change in platelet count nor in blood paf levels (55 +/- 10 vs. 52.5 +/- 20 pg ml-1, P greater than 0.05). Pre-treatment with indomethacin alone (group III) did not protect the animals against the haematological changes induced by the heparin-protamine complexes. Pre-treatment with the paf receptor antagonist, alone or in association with indomethacin, delayed the occurrence of thrombocytopenia 3 min after protamine administration but the leucopenia was the same as in group I. This study demonstrated that paf is implicated in the immediate thrombocytopenia occurring after protamine reversal of heparin in rabbit.     

体外循环中肝素、鱼精蛋白对血小板的激活及抑肽酶的抑制作用

目的研究在体外循环中肝素化及鱼精蛋白中和时血小板的激活以及应用抑肽酶对这种激活的抑制作用。方法２０例心脏瓣膜置换术患者随机等分为两组：对照组和抑肽酶组，分别于肝素化及应用鱼精蛋白前后检测血小板胞浆游离钙浓度，磷脂酶Ａ２活性及血浆血栓素水平。结果上述指标在肝素化及鱼精蛋白中和后均显著升高，其中鱼精蛋白中和时升高幅度更大，应用抑肽酶对肝素及鱼精蛋白所引起的上述改变均有显著抑制作用。结论抑肽酶对肝素和鱼精蛋白所致的血小板激活有显著抑制作用，这可能与抑肽酶在体外循环中的止血作用有关。     

异氟烷预处理对心肺转流术后早期肺损伤的影响

Objective To observe the effects of isoflurane preconditioning against cardiopulmonary bypass (CBP)-induced early injury of lungs.Methods Sixteen patients undergone cardiac valve replacement were randomly divided into control group (group C,n =8) or isoflurane group (group I,n =8).Midazolam,fentanyl and vecuronium were used to maintain anesthesia.Isoflurane was inhaled for at least 30 min before CBP and then eluted out in group I,while only pure oxygen was inhaled in group C.Serum TNF-α,P-selectin,MDA and myeloperoxidase (MPO) were measured and respiratory index (RI,PA-aDO2/PaO2) was calculated according to blood gas analysis 10 min after anesthesia induction (T1),30 min (T2) and 180 min (T3) after vena cava opened,respectively.Before chest closure a bit of lung tissue was taken for detection of gap junction protein 43 (Cx43) and pathological examination.Results Serum TNF-α,P-selectin,MDA,MPO and RI significantly increased after CPB (T2-3) in both groups (P＜0.05-0.01),with less increasing extent in group I than in group C.There were no differences in distribution,colorful gap junction of lungs and CX43 expression in both groups.Pathological examination showed obvious edema in alveolar space,destroyed alveolar structure,severe neutrophil accumulation and erythrocyte infiltration in both groups.Conclusion Isoflurane preconditioning attenuates the oxidative stress response and lung inflammatory reaction,exerting protection of lungs against CBP-induced early injury.     

Limitation of thrombin generation, platelet activation, and inflammation by elimination of cardiotomy suction in patients undergoing coronary artery bypass grafting treated with heparin-bonded circuits

OBJECTIVE: Reports evaluating the efficacy of heparin-bonded circuits to blunt inflammation, platelet dysfunction, and thrombin generation in response to cardiopulmonary bypass have varied. We hypothesized that this variability may in part be related to the use of cardiotomy suction, which has been demonstrated to reintroduce procoagulant and proinflammatory factors into the systemic circulation during cardiopulmonary bypass. A prospective, randomized study was undertaken to evaluate the specific effects of cardiotomy suction. METHODS: Thirty-six patients undergoing first-time, nonemergency coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to one of three treatment groups: group I, non-heparin-bonded circuits with the use of cardiotomy suction (n = 12); group II, Duraflo II (BCR-3500; Jostra Bentley Corp, Irvine, Calif) heparin-bonded circuits with cardiotomy suction (n = 12); and group III, Duraflo II heparin-bonded circuits without cardiotomy suction (n = 12). Thrombin generation, neutrophil activation (polymorphonuclear elastase), platelet activation (beta-thromboglobulin), and neuronal injury (neuron-specific enolase) were analyzed by enzyme-linked immunosorbent assays after cardiopulmonary bypass and compared with prebypass levels. Results are presented as mean +/- SEM. RESULTS: Prebypass levels of all markers were similar among treatment groups. However, postbypass levels were significantly and consistently highest in group I relative to groups II and III. Thrombin generation levels were 5.0 +/- 0.9 nmol/L in group I, 3.0 +/- 0.6 nmol/L in group II, and 1.5 +/- 0.1 nmol/L in group III (P <.05 vs group II and P <.001 vs group I). Polymorphonuclear elastase levels were 307 +/- 64 microg/L in group I, 128 +/- 24 microg/L in group II (P <.05 vs group I), and 75 +/- 14 microg/L in group III (P <.001 vs group I). beta-Thromboglobulin levels were 2692 +/- 401 IU/mL in group I, 912 +/- 99 IU/mL in group II (P =.001 vs group I), and 646 +/- 133 IU/mL in group III (P =.001 vs group I). Neuron-specific enolase levels were 9.8 +/- 0.9 ng/mL in group I, 10.5 +/- 1.6 ng/mL in group II, and 4.2 +/- 0.5 ng/mL in group III (P =.001 vs groups I and II). CONCLUSIONS: Use of cardiotomy suction resulted in significant increases in thrombin, neutrophil, and platelet activation, as well as the release of neuron-specific enolase, after cardiopulmonary bypass. Limiting increases in these markers would be best accomplished by eliminating cardiotomy suction and routinely using heparin-bonded circuits whenever possible.     

Effects of aprotinin on plasma levels of neutrophil elastase and postoperative blood loss in cardiac surgery

This study evaluated the effects of aprotinin on plasma levels of elastase, platelet count, fibrinogen levels and postoperative bleeding. Thirty cardiac surgery patients were randomly chosen for this study. The protease inhibitor aprotinin was given in high doses to 20 patients before and during cardiopulmonary bypass; 10 patients served as the control group. Mean patient age and body weight was similar in both groups. There were no significant inter-group differences in the total cardiopulmonary bypass and cross-clamp times. Mean(s.e.m.) elastase levels were significantly raised in the control group (161.9(2.57)μg/l) compared with the treated group (148.2(3.29)μg/l) at 30 min of cardiopulmonary bypass (P< 0.01) and rose even further at the end of cardiopulmonary bypass, after protamine infusion, and 24h postoperatively (P < 0.001). Platelet counts decreased more in the control group (P < 0.001). Serum fibrinogen levels were significantly lower in the controls during and just after cardiopulmonary bypass (P < 0.01). Postoperative blood loss was significantly less in the aprotinin-treated patients (315(25) ml) compared with the controls (589(154) ml) (P < 0.05). Aprotinin appears to inhibit elastase release and decrease postoperative blood loss. Copyright © 1996 The International Society for Cardiovascular Surgery.     

Insulin-like growth factor 1 improves the relationship between systemic oxygen consumption and delivery in piglets after cardiopulmonary bypass

OBJECTIVE: We sought to assess the effects of insulin-like growth factor 1 on the balance between systemic oxygen consumption and oxygen delivery after cardiopulmonary bypass in piglets. METHODS: Twelve piglets weighing 4.5 to 8.3 kg undergoing hypothermic (28 degrees C) cardiopulmonary bypass for 70 to 120 minutes with 40 minutes of aortic crossclamping were studied before and during the first 6 hours after cardiopulmonary bypass. Oxygen consumption was continuously measured by an indirect calorimeter, Deltatrac II MBM-200 Metabolic Monitor (Datex Division Instrumentarium, Helsinki, Finland). Oxygen delivery and cardiac output were calculated from oxygen consumption and the arterial and mixed venous oxygen contents sampled before and every 30 minutes after cardiopulmonary bypass. Oxygen extraction ratio was derived by the ratio of oxygen consumption to oxygen delivery. Arterial blood lactate was measured before and every 30 minutes after cardiopulmonary bypass. Six animals were randomly assigned to receive an intravenous infusion of insulinlike growth factor 1 at 1.2 mg/h from 1 to 6 hours after cardiopulmonary bypass; the remaining 6 served as a control group. RESULTS: Relative to the control group, intravenous infusion of insulin-like growth factor 1 significantly reduced oxygen consumption (P =.02) and increased cardiac output (P =.016) and oxygen delivery (P =.049) during the first 6 hours after surgery with hypothermic cardiopulmonary bypass. As a result, oxygen extraction was significantly decreased (P =.012). CONCLUSIONS: Intravenous infusion of insulin-like growth factor 1 improved oxygen transport by reducing oxygen consumption as well as increasing cardiac output and oxygen delivery during the first 6 hours after cardiopulmonary bypass in piglets. This may have important clinical implications for the care of critically ill children after surgery with cardiopulmonary bypass.     

Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?

Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20–28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28°C core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 μg/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO₂) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0±5.3 nmol/g of tissue rose to 67.6±5.7 nmol/g of tissue after weaning from CPB in group I (P=0.028). In group II MDA values also increased from 43.1±4.3 to 52.4±5.7 nmol MDA/g of tissue after weaning from CPB (P=0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P=0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1±0.2, significantly lower than in the control group (6.8±0.4), (P=0.01). AaDO₂ increased significantly in group I (P=0.028). There was no statistically significant difference (P=0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P<0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass.     

Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation.

The systemic inflammatory response to cardiopulmonary bypass was assessed in 20 patients who underwent elective coronary artery bypass grafting with flat-sheet membrane oxygenation (group I; n = 10; age, 59 +/- 5 years) or bubble oxygenation (group II; n = 10; age, 62 +/- 8 years). The duration of cardiopulmonary bypass was 46 +/- 12 minutes in group I and 47 +/- 15 minutes in group II. Plasma interleukin-6, plasma interleukin-1 beta, transpulmonary leukocyte counts, pulmonary hemodynamic variables, and respiratory index were determined in all patients perioperatively. The plasma interleukin-6 response (median [range]) was similar in both groups at the end of the operation, peaked 4 hours postoperatively (99 [30 to 320] pg/mL in group I; 123 [21 to 300] pg/mL in group II; p greater than 0.05), and remained elevated 48 hours postoperatively (76 [9 to 140] pg/mL in group I; 65 [25 to 159] pg/mL in group II; p greater than 0.05). No significant interleukin-1 beta response was demonstrated. Pulmonary neutrophil and lymphocyte sequestration was observed on commencement of cardiopulmonary bypass in group II but did not occur in either group on discontinuation of cardiopulmonary bypass. Pulmonary vascular resistance at the end of the operation (82 [48 to 320] dynes.s.cm-5 in group I; 119 [54 to 385] dynes.s.cm-5 in group II; p greater than 0.05) was similar to preoperative values (151 [30 to 327] dynes.s.cm-5 in group I; 185 [62 to 291] dynes.s.cm-5 in group II; p greater than 0.05). The respiratory index at the end of the operation was similarly and significantly increased in both groups (1.26 [0.92 to 4.17] in group I; 1.44 [0.73 to 3.30] in group II).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.