自体肺氧合体外循环防止炎症反应性肺损伤

目的 探讨采用自体肺代替人工氧合器的体外循环技术是否比常规体外循环对肺组织有更好的保护作用。方法12只小猪随机分为实验组和对照组。实验组用自体肺代替人工氧合器，对照组按常规体外循环方法，分别转流135min，主动脉阻断60min，测定实验前、后肺静态顺应性、肺动-静脉氧差，检测灌注液中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6变化，测定肺组织湿，干比和观察肺病理学改变。结果两组体外循环后的肺静态顺应性均下降、肺动-静脉氧分压差增大，灌注液中TNF-α和IL-6含量增加，但两组相比，实验组的改变显著轻于对照组。肺组织标本显示，实验组的肺湿，干比明显低于对照组，光镜和电镜观察肺损伤程度也较轻。结论自体肺能够耐受非搏动性灌注而代替人工氧合器进行体外循环且可显著减轻因肺的缺血再灌注以及因采用人工氧合器所引起的炎症反应性肺损伤，对肺组织有较好的保护作用。     

Continuous pulmonary perfusion during cardiopulmonary bypass prevents lung injury in infants

BACKGROUND: Lung injury after cardiopulmonary bypass is a serious complication for infants with congenital heart disease and pulmonary hypertension. Excessive neutrophil sequestration in the lung occurring after reestablishment of pulmonary circulation implies that interaction between neutrophils and pulmonary endothelium is the major cause of lung injury. METHODS: Thirty infants with either ventricular septal defect or atrioventricular septal defect and with pulmonary hypertension were enrolled in this study. We performed continuous pulmonary perfusion during total cardiopulmonary bypass on 16 patients (perfused group) and conventional cardiopulmonary bypass on 14 patients (control group). PaO2/FiO2 and neutrophil counts were assessed from immediately before surgery to 24 hours after termination of cardiopulmonary bypass. RESULTS: PaO2/FiO2 was higher in the perfused group than in the control group, and the difference was significant throughout the study period. Neutrophil counts decreased below prebypass values in both groups at 30 minutes after aortic unclamping, and the difference was significant in the control group but was not in the perfused group. Duration of postoperative ventilatory support was significantly less in the perfused group. CONCLUSIONS: Our study demonstrates that arrested pulmonary circulation during cardiopulmonary bypass is the major risk factor of lung injury and that continuous pulmonary perfusion is effective in preventing lung injury.     

肝素化膜肺和甲基强的松龙预处理对心肺转流后肺损伤的防治作用

目的观察肝素化膜肺和甲基强的松龙预处理对炎性细胞因子的影响和对心肺转流(CPB)后肺损伤的防治作用。方法30例择期行双瓣膜置换的病人,随机均分为三组:肝素化膜肺组(H组)、甲基强的松龙组(M组)和对照组(C组)。术中持续监测ECG、HR、SpO2、MAP、CVP、心输出量(CO);术前、CPB前、主动脉开放前、开放后0·5、1、2、6h采取动脉血测定细胞因子如肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的变化;术前、CPB前、主动脉开放后1·5、2、6h采血测定动脉血气,氧合指数(PaO2/FiO2),同期监测气道压并计算肺的顺应性。结果三组病人在主动脉开放前、开放后0·5、1、2、6h时TNF-α、IL-1β、IL-6均较术前显著升高(P<0·05,P<0·01)。主动脉开放前、开放后0·5、1、2、6h时M组TNF-α、IL-1β、IL-6均较C组显著降低(P<0·05,P<0·01);主动脉开放后0·5、1hH组TNF-α、IL-1β、IL-6较C组明显降低(P<0·05),且M组在开放后各时点TNF-α、IL-1β、IL-6较H组降低更明显(P<0·01)。三组开放后各时点较CPB前气道阻力轻度升高,但三组间差异无显著意义。主动脉开放后1·5、2、6h三组病人和术前相比PaO2/FiO2显著降低(P<0·05,P<0·01);与H组、C组相比,M组在主动脉开放后1·5、2、6h时PaO2/FiO2显著增加(P<0·01)。结论CPB可引起以炎性细胞因子升高为特征的全身性炎症反应,产生肺损伤;单纯肝素涂抹膜肺轻度降低细胞因子变化,但对肺功能无明显保护作用;小剂量甲基强的松龙(5mg/kg)可有效抑制细胞因子的升高,促进肺功能的恢复。     

Biocompatibility of silicone-coated oxygenator in cardiopulmonary bypass

BACKGROUND: This study was designed to analyze the biocompatibility of silicone-coated oxygenators using inflammatory response as the outcome measure, and to investigate whether the silicone-coated oxygenators perform better in terms of postoperative organ dysfunction. METHODS: The 32 patients who underwent cardiopulmonary bypass (CPB) were divided into 3 groups: group A (n = 10), heparin-coated circuit with silicone-coated oxygenator; group B (n = 11), whole heparin-coated circuit; and group C (n = 11), whole untreated circuit. The plasma concentrations of the proinflammatory markers, made of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8), terminal complement complex (C5b-9), and polymorphonuclear elastase (PMN-E), were measured by enzyme-linked immunosorbant assay. RESULTS: All proinflammatory markers were significantly lower in groups A and B than in group C, especially C5b-9 and PMN-E concentrations, which were significantly lower in group A than in group B. The alveolar-arterial oxygen gradients (A-aDO2) and the respiratory index were significantly better in group A than in group C. In group B, however, only the A-aDO2 was significantly better than in group C. The duration of intubation and the length of stay in the intensive care unit stay were significantly shorter in groups A and B than in group C. CONCLUSIONS: Silicone-coated oxygenators are biocompatible and prevent postoperative organ dysfunction.     

Effects of inosine on reperfusion injury after cardiopulmonary bypass

Objective  

Inosine, a break-down product of adenosine has been recently shown to exert inodilatory and anti-inflammatory properties. Furthermore inosine might be a key substrate of pharmacological post-conditioning. In the present pre-clinical study, we investigated the effects of inosine on cardiac function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation.     

An oxygenator for cardiopulmonary bypass in the rat

A minature bubble oxygenator with integral heat exchange has been developed for high flow, normothermic, total cardiopulmonary bypass in rats: priming volume, 25 ml; flow rate, up to 260 ml/kg/min; survival after a 2-hr total bypass. It is thus possible to use rats for cardiothoracic surgical research and to make use of the many advantages of a standardized small-animal model, in particular for large-series work, in a field previously limited to large animals such as dogs, pigs, and calves.     

Membrane oxygenator exhaust capnography for continuously estimating arterial carbon dioxide tension during cardiopulmonary bypass

Typically, the standard practice for measuring the arterial blood carbon dioxide tension (PaCO2) during cardiopulmonary bypass (CPB) is to take intermittent blood samples for analysis by a bench blood gas analyzer. Continuous inline blood gas monitors are available but are expensive. A potential solution is the capnograph, which was evaluated by determining how accurately the carbon dioxide tension in the oxygenator exhaust gases (PECO2) predicts PaCO2. A standard capnograph monitoring line was attached to the exhaust port of the membrane oxygenator. During CPB, the capnograph reading and arterial blood temperature were recorded at the same time as routine arterial blood gases were taken. One hundred fifty-seven blood samples were collected from 78 patients. A good correlation was found between the PECO2 and the temperature corrected PaCO2 (r2 = 0.833, P < .001). There was also a reasonable degree of agreement between the PECO2 and the temperature corrected PaCO2 during all phases of CPB: accuracy (bias or mean difference between PaCO2 and PECO2) of -1.2 mmHg; precision (95% limits of agreement) of +/- 4.7 mmHg. These results suggest that oxygenator exhaust capnography may be a simple and inexpensive adjunct to the bench blood gas analyzer in continuously estimating PaCO2 of a clinically useful degree of accuracy during CPB.     

黏附分子与心肺转流术肺损伤

急性肺损伤是心肺转流术(cardiopulmonary by-pass,CPB)后最常见的并发症,其中白细胞在肺内的“扣留”起到了主要作用,而细胞黏附分子参与了白细胞渗出及活化的各个环节。现就有关黏附分子与CPB肺损伤关系的研究作以下综述,并探讨目前抗黏附分子在这领域的应用,旨在进一步揭示C     

Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model.

OBJECTIVES: Cardiopulmonary bypass (CPB) induces systemic inflammatory response with neutrophil activation and subsequent lung dysfunction. Rolipram, a selective phosphodiesterase type 4 inhibitor, blocks the decrease in levels of cyclic adenosine monophosphate associated with neutrophil activation. Here, we tested the protective effect of rolipram on CPB-induced lung injury in the rat. METHODS: Rats were divided into three groups: control (C), rolipram (R) and sham (S). In the C and R groups, animals underwent CPB at a flow rate of 60 ml/kg per min for 60 min followed by another 60-min observation, whereas the S group rats were sustained for 120 min only with median sternotomy and the placement of cannulae for CPB. Rolipram (40 microg/kg per min) was administered to the R group rats by continuous intravenous infusion from 10 min before the establishment of CPB to the end of the experiment. RESULTS: The R and S groups showed significantly higher mean arterial oxygen pressure and lower mean lung wet-to-dry weight ratio compared with those observed in the C group (R: 489+/-44 or S: 527+/-55 vs. C: 287+/-185, and R: 5.0+/-0.4 or S: 4.7+/-0.3 vs. C: 5.9+/-0.5, respectively; (P < 0.01). Although CD11b expression levels on circulating neutrophils in the C group doubled after CPB, those in the R and S groups remained almost the same (P = 0.0008). Intrapulmonary tumor necrosis factor-alpha concentrations (pg/microg protein) in the C group tended to be higher than those observed in the R and S groups (R: 5.2+/-2.1, S: 5.0+/-2.1 and C: 8.9+/-5.4; R vs. C: P = 0.09 and S vs. C: P = 0.08). Pathological study of lungs revealed that more alveolar hemorrhage and neutrophil accumulation were observed in the C group compared to the R and S groups. CONCLUSIONS: These results suggest that rolipram prevents acute lung injury via the inhibition of neutrophil activation during and after CPB in this setting of a rat model.     

Does aprotinin reduce lung reperfusion damage after cardiopulmonary bypass?

OBJECTIVE: The role of aprotinin in the prevention of lung reperfusion injury was investigated in the patients undergoing cardio-pulmonary bypass (CPB) for coronary artery bypass grafting (CABG) operations. METHODS: The study was planned randomly and prospectively. Two hundred milliliters of physiological saline solution was added to the prime solution of patients in group I (n=10) whereas, 200 ml aprotinin (Trasylol, Bayer AG) was given to patients in group II (n=10). In order to measure lung tissue malondialdehyde (MDA) levels, glutathion peroxidase (GSH-Px) activity levels and polymorphonuclear leukocytes (PMNs) numbers, lung tissue samples were taken before CPB and 5 min after removing the cross clamp. In addition, alveolo-arterial oxygen difference (AaDO(2)) for tissue oxygenation was calculated by obtaining arterial blood gas samples. RESULTS: MDA levels before CPB increased from 41.72+/-21.00 nmol/g tissue to 66.71+/-13.44 nmol/g tissue in group I and from 43.44+/-5.16 nmol MDA/g tissue to 53.22+/-10.95 nmol MDA/g tissue in group II after cross clamp removal (P=0.001 and P=0.021, respectively). The increase in group II was found to be significantly lower than group I (P=0.048). With the initiation of reperfusion, GSH-Px activity decreased in group I from 3.05+/-0.97 to 2.31+/-0.46 U/mg protein (P=0.015) whereas GSH-Px activity in group II decreased from 3.18+/-1.01 to 2.74+/-0.81 U/mg protein (P=0. 055). This decrease in the group II was less than group I (P=0.049). AaDO(2) significantly increased in the group I and II (P=0.012 and P=0.020, respectively), but elevation in the group I was significant than in the Group II (P=0.049). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly following removal of cross clamp in both groups (P=0. 001). The increase in group I was significantly larger than in group II (P=0.050). CONCLUSION: Results represented in our study indicate that addition of aprotinin (2 million units) into the prime solution during CPB can reduce lung reperfusion injury.     

Asanguineous reperfusion in a canine model of cardiopulmonary bypass and controlled postischemic work

This study was designed to test the hypothesis that asanguineous reperfusion with a standard crystalloid cardioplegic solution results in improved myocardial salvage after a period of global ischemia. Four groups of 6 dogs each were placed on cardiopulmonary bypass. Control group A (work only) performed two hours of controlled work by contracting against a saline-filled left intraventricular balloon. Control group B (ischemia only) underwent 45 minutes of global normothermic ischemia before simple blood reperfusion while supported on bypass. Groups C and D were subjected to ischemia and reperfusion as in group B, followed by controlled work stress as in group A. Group D, however, received 500 mL of St. Thomas' Hospital solution immediately before blood reperfusion. Morphological analysis showed no significant injury in groups A and B, whereas group C had 11.4% +/- 2.4% necrosis of heart mass versus 2.5% +/- 1.1% in group D (p less than 0.001). Biochemical data from left ventricular biopsies showed no significant differences between groups B, C, and D. Functional analyses showed deterioration of diastolic compliance in group C (p less than 0.05), although a significant difference in systolic functional indexes could not be detected. Myocardial protection and salvage was improved by initial reperfusion with an asanguineous cardioplegic solution versus reperfusion with blood alone.     

抗ICAM-1单抗对体外循环下犬心肌的保护作用

目的 探讨抗ICAN-1单抗对体外循环下心肌的保护作用及可能机制.方法 应用犬体外循环心肌再灌注损伤模型,比较含抗ICAM-1单抗的灌注液干预前后心功能以及心肌组织或血浆中SOD、NDA、CPK、ATP、LA等的变化.结果 体外循环再灌注后,心功能减退,心肌组织中NDA、LA增加,SOD及ATP减少,而血浆CPK增加,发生再灌注损伤.抗ICAN-1单抗干预后心功能显著改善,心肌或血浆中原本升高的MDA、CPK、LA下降,而下降的SOD及ATP增加.结论 抗ICAN-1单抗可减少体外循环再灌注时的白细胞黏附,降低心肌自由基水平,减轻心肌损伤,产生心肌保护作用.     

Biocompatibility of Trillium Biopassive Surface-coated oxygenator versus uncoated oxygenator during cardiopulmonary bypass.

OBJECTIVE: To determine if the Trillium Biopassive Surface (Medtronic Cardiopulmonary, Minneapolis, MN) coating added to the cardiopulmonary bypass oxygenator reduces inflammatory mediators, blood loss, and transfusion requirements. DESIGN: Prospective, randomized, and blinded human trial. SETTING: Tertiary care academic medical center. PARTICIPANTS: Thirty adult patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Patients received visually identical coated or uncoated oxygenators. MEASUREMENTS AND MAIN RESULTS: Hemoglobin, hematocrit, leukocyte count, platelet count, terminal complement complex, complement activation, myeloperoxidase, beta-thromboglobulin, prothrombin fragment 1.2, plasmin-antiplasmin, heparin concentration, activated coagulation time, and fibrinogen concentration were measured. Blood loss and blood product usage were recorded. In both groups, there were significant inflammatory alterations with the initiation of cardiopulmonary bypass. In the postprotamine samples, the coated oxygenator group had small but significant increases in hemoglobin, hematocrit, and leukocyte count. There were no differences in inflammatory mediators, blood loss, or transfusion requirements between the coated and uncoated groups. CONCLUSION: This human trial of Trillium Biopassive Surface-coated oxygenators did not show clinical benefits or clinically important biochemical results.     

Strategies to prevent intraoperative lung injury during cardiopulmonary bypass

During open heart surgery the influence of a series of factors such as cardiopulmonary bypass (CPB), hypothermia, operation and anaesthesia, as well as medication and transfusion can cause a diffuse trauma in the lungs. This injury leads mostly to a postoperative interstitial pulmonary oedema and abnormal gas exchange. Substantial improvements in all of the above mentioned factors may lead to a better lung function postoperatively. By avoiding CPB, reducing its time, or by minimizing the extracorporeal surface area with the use of miniaturized circuits of CPB, beneficial effects on lung function are reported. In addition, replacement of circuit surface with biocompatible surfaces like heparin-coated, and material-independent sources of blood activation, a better postoperative lung function is observed. Meticulous myocardial protection by using hypothermia and cardioplegia methods during ischemia and reperfusion remain one of the cornerstones of postoperative lung function. The partial restoration of pulmonary artery perfusion during CPB possibly contributes to prevent pulmonary ischemia and lung dysfunction. Using medication such as corticosteroids and aprotinin, which protect the lungs during CPB, and leukocyte depletion filters for operations expected to exceed 90 minutes in CPB-time appear to be protective against the toxic impact of CPB in the lungs. The newer methods of ultrafiltration used to scavenge pro-inflammatory factors seem to be protective for the lung function. In a similar way, reducing the use of cardiotomy suction device, as well as the contact-time between free blood and pericardium, it is expected that the postoperative lung function will be improved.     

Partial cardiopulmonary bypass in rats using a hollow fibre oxygenator

Despite new minimally invasive techniques, cardiopulmonary bypass (CPB) is still necessary for many major operations in the field of cardiac surgery. Unwanted side effects of CPB are well known but poorly understood. We therefore developed a rodent model to study the pathophysiology of these potential complications. Male Fischer rats were anaesthetized, intubated and ventilated. The carotid artery and jugular vein were cannulated. The blood was actively drained from the venous circulation and further transferred by a miniaturized roller pump to a hollow fibre oxygenator and back to the animal via the carotid artery. The roller pump produces a pulsatile blood flow between 5 and 40 ml/min. The surface of the hollow fibre oxygenator is 0.025 m2. The priming volume (Ringer solution) of the whole system is 12 ml. Animals were catheterized and brought in partial bypass for a mean of 50+/-15 min. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. This technical study demonstrates the feasibility of a small animal model of CPB. The main improvement over existing techniques is the use of a highly effective hollow fibre oxygenator with a minimized priming volume. Therefore, no additional animals are needed as blood donors.     

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.     

Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass. To determine whether leukocyte depletion could prevent this injury, we used a dog model simulating routine cardiac operations. Mongrel dogs (11 to 17 kg) were subjected to cardiopulmonary bypass with a bubble oxygenator and cooled to 27 degrees C. After aortic crossclamping and cardioplegic arrest for 90 minutes, control animals (n = 5) were rewarmed and weaned from bypass, and their condition was then stabilized for 90 minutes. Leukocyte-depleted animals (n = 5) had a leukocyte filter incorporated in the bypass circuit. During bypass, circulating leukocyte counts decreased by 60% in control dogs, and by 97% in leukocyte-depleted animals. Free radical generation (estimated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by leukocyte depletion during and after bypass. Total hemolytic complement activity and the titer of C5 decreased markedly immediately after the onset of bypass in both the control and leukocyte-depleted animals. Pulmonary function after bypass was better preserved in leukocyte-depleted animals. These data suggest that depletion of circulating leukocytes contributes to lung injury during cardiopulmonary bypass and is associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduced the pulmonary injury seen after cardiopulmonary bypass.