Bacterial translocation secondary to small intestinal mucosal ischemia during cardiopulmonary bypass. Measurement by diamine oxidase and peptidoglycan.

OBJECTIVES: To demonstrate that small intestinal mucosal ischemia occurs during cardiopulmonary bypass by measuring serum diamine oxidase activity, an index of small intestinal mucosal ischemia, in perioerative patients undergoing cardiovascular surgery with and without cardiopulmonary bypass. METHODS: Twelve successive patients who underwent coronary artery bypass grafting with cardiopulmonary bypass (Group I) were compared to 10 patients who underwent off-pump coronary artery bypass grafting (Group II). Serum diamine oxidase activity, blood lactate concentration, and serum peptidoglycan concentration were measured perioperatively. RESULTS: Serum diamine oxidase activity rose after the start of cardiopulmonary bypass and continued to rise throughout cardiopulmonary bypass in Group I, while activity was unchanged in Group II. The serum lactate concentration mirrored the change in the diamine oxidase activity in both groups. The peptidoglycan concentration in Group I rose after the start of cardiopulmonary bypass and returned to near normal concentrations after surgery. CONCLUSIONS: The parallel rise in diamine oxidase activity and the serum lactate concentration in Group I implies that ischemic injury to the mucosa of the small intestine occurs during cardiopulmonary bypass, and the rise in the serum peptidoglycan concentration indicates that bacteremia did occur. Thus, cardiopulmonary bypass causes hypoperfusion of small intestinal mucosa and consequently bacterial translocation.     

双歧三联活菌预处理对体外循环后大鼠肠黏膜屏障功能的影响

目的 探讨双歧三联活菌预处理对体外循环(CPB)后大鼠小肠黏膜屏障功能的影响.方法 成年雄性SD大鼠24只,体重350～450 g,随机分为3组(n=8):假手术组(S组)、CPB组和双歧三联活菌预处理组(P组).CPB开始前7 d,P组每天用双歧三联活菌2 ml(含活菌数1×10~7 CFO)灌胃,S组和CPB组用生理盐水2 ml灌胃.第8天进行CPB 60 min.CPB结束后2 h时处死大鼠,抽取门静脉血,采用分光光度法测定血浆二胺氧化酶活性和D-乳酸浓度,鲎试验偶氮显色法测定内毒素浓度,放免法测定血浆TNF-α和IL-6的浓度.取腔静脉血,肝、肺、肾组织及肠系膜淋巴结,分别接种于血平皿上培养,24 h后鉴定细菌生长情况及细菌种类,光镜下观察小肠上皮组织病理学.结果 与S组相比,CPB组和P组血浆D-乳酸、内毒素、TNF-α和IL-6的浓度、二胺氧化酶活性及细菌易位率升高(P<0.05);与CPB组相比,P组上述各指标降低(P<0.05).病理结果显示P组小肠上皮组织损伤程度较CPB组明显减轻.结论 双歧三联活菌预处理可在一定程度上抑制炎性反应,保护CPB后大鼠小肠黏膜屏障功能.     

双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响

目的 探讨双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响.方法 择期拟行体外循环下瓣膜置换术患者40例,年龄30～64岁,体重40～80 Kg,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为对照组(C组)和双歧三联活菌组(Y组),每组20例.Y组于术前7d开始,每日口服双歧三联活菌制剂(每片含活菌数0.5×107 CFU)4片,每日3次,连服7 d.分别于体外循环前(T1)、主动脉开放10 min(T2)、停体外循环即刻(T3)、术后2、6和18 h(T4～6)时采集中心静脉血样5 ml,采用紫外分光光度法测定血浆二胺氧化酶(DAO)活性和D-乳酸浓度,酶联免疫吸附法测定血浆IL-6和IL-10的浓度.结果 与T1时比较,两组其余时点血浆DAO活性和D-乳酸IL-6和IL-10浓度均升高(P＜0.05);与C组比较,Y组T2～5时血浆DAO活性和D-乳酸浓度降低,T4,5时血浆IL-6和IL-10浓度降低(P＜0.05).结论 双歧三联活菌可在一定程度上抑制炎性反应,改善体外循环心脏直视手术患者的肠黏膜屏障功能.

Abstract：

Objective To investigate the effects of probiotics on the plasma diamine oxidase (DAO) activity and D-lactate, IL-6 and IL-10 levels in patients undergoing open heart surgery under cardiopulmonary bypass (CPB) , trying to elucidate the mechanism of protective effect of probiotics against CPB- induced injury to intestinal mucosal barrier. Methods Forty ASA Ⅱ - Ⅲ patients of both sexes aged 30-64 yr weighing 40-80 kg undergoing open heart operation under CPB were randomized into 2 groups ( n = 20 each) : control group (group C) and probiotics group (group Y) . Group Y received Jinshuangqi (Bifid Triple Viable containing bifido-bacterium, lacto-bacillus, streptococcus thermophiles) 4 pills 3 times a day for 7 days before operation. Venous blood samples were taken from CVP line before operation (T1 ), at 10 min after aortic unclamping (T2 ) and at the end of CPB (T3 ) and at 2, 6, 18 h (T4,5,6) after operation for determination of plasma DAO activity and D-lactate, IL-6 and IL-10 levels.Results Plasma DAO activity, D-lactate, IL-6 and IL-10 levels were significantly increased after CPB was started at T2-6 as compared with the baseline values at T1 in both groups. Plasma DAO activity and D-lactate level were significantly lower at T2-5 , the plasma IL-6 level was significantly lower and plasma IL-10 level higher at T4,5 in group Y than in group C. Conclusion Probiotics can protect intestinal mucosal barrier in patients undergoing open heart surgery under CPB and attenuate inflammatory response.     

Ginsenosides compound (shen-fu) attenuates gastrointestinal injury and inhibits inflammatory response after cardiopulmonary bypass in patients with congenital heart disease

OBJECTIVE: This study was undertaken to demonstrate that gastrointestinal mucosal injury occurs during cardiopulmonary bypass in children, increasing systemic inflammatory responses, and to determine whether shen-fu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) could attenuate gastrointestinal mucosal injury and subsequent inflammatory responses. METHODS: Twenty-four children undergoing heart surgery for congenital heart defects were randomly assigned to groups C (placebo control, n = 12) and G (1.35 mg/kg ginsenosides compound intravenously before and throughout the course of cardiopulmonary bypass, n = 12). Central venous blood samples were taken before cardiopulmonary bypass and at 60 and 120 minutes after aortic declamping (reperfusion). Gastric intramucosal pH was measured by perioperative tonometry. Plasma lipid peroxidation product malondialdehyde, myocardium-specific creatine kinase isoenzyme MB activity, diamine oxidase, lipopolysaccharide, and interleukin 6 were all measured. RESULTS: Significant decrease in gastric intramucosal pH and increase in plasma diamine oxidase were seen during reperfusion in group C, accompanied by increases in plasma levels of malondialdehyde, lipopolysaccharide, interleukin 6, and creatine kinase isoenzyme MB (P < .01 vs before cardiopulmonary bypass). Shen-fu injection significantly attenuated these changes (P < .05). Consequently, fewer patients in group G (2/12) than in group C (7/12) needed postoperative inotropic support. Postoperative intensive care unit stay was shorter in group G than in group C. A tight positive correlation was seen between diamine oxidase and interleukin 6 at 60 minutes after aortic declamping and between diamine oxidase and lipopolysaccharide at 120 minutes after aortic declamping (r = 0.79, P < .0001). CONCLUSION: Ginsenosides compound may attenuate gastrointestinal injury and inhibit inflammatory response after cardiopulmonary bypass in patients with congenital heart disease.     

Cardiopulmonary bypass in humans--jejunal mucosal perfusion increases in parallel with well-maintained microvascular hematocrit

BACKGROUND: An imbalance between splanchnic oxygen supply and demand occurs during cardiopulmonary bypass (CPB) in man, which might disrupt the intestinal mucosal barrier function. The aim of the present study was to evaluate the effects of mild hypothermic CPB on intestinal mucosal perfusion in man undergoing cardiac surgery. Additionally we aimed to identify variables, which independently could predict changes of intestinal mucosal microcirculatory variables during CPB. METHODS: Jejunal mucosal perfusion (JMP), jejunal mucosal hematocrit (JMHt), red blood cell (RBC) velocity and arteriolar vasomotion using endoluminal jejunal laser Doppler flow metry were studied in eight cardiac surgical patients before and during CPB at a temperature of 34 degrees C. RESULTS: Cardiopulmonary bypass and the accompanied hemodilution (25-30%) induced a 44% increase in JMP (P < 0.05) and a 42% increase in RBC velocity (P < 0.01), with no change in JMHt. The oscillation amplitude of JMP, at a fundamental frequency of 2.8 cycles min(-1), increased with 175% (P < 0.05) during CPB. Splanchnic oxygen extraction increased by 64% during CPB (P < 0.05). Stepwise multiple regression analysis identified systemic hematocrit, arterial O2 and CO2 tension and splanchnic oxygen extraction as independent predictors of RBC velocity during CPB (R2=0.63, P < 0.001). The oscillation amplitude of JMP was predicted by RBC velocity and splanchnic oxygen extraction (R2= 0.68, P <0.0001). CONCLUSIONS: The increase in RBC velocity and enhanced arteriolar vasomotion, as well as maintained jejunal mucosal hematocrit, are microcirculatory, compensatory mechanisms for the splanchic oxygen supply/demand mismatch seen during cardiopulmonary bypass in humans.     

The effect of intestinal autotransplantation on serum diamine oxidase activity

Circulating levels of diamine oxidase (DAO), a mucosal enzyme found primarily in the small intestine, have been shown to reflect intestinal mucosal damage in a variety of disease states. Our aim was to assess the usefulness of both basal and postheparin DAO activity as a marker of intestinal allograft rejection by studying the influence of the nonrejection effects of intestinal transplantation on these activities. This separation of the immunological from all other effects of transplantation was achieved by studying 11 dogs who had undergone autotransplantation of the small intestine and 11 unoperated controls. Basal serum DAO activity increased during the first 3 postoperative days following autotransplantation (20.5 +/- 0.7 units/ml on Day 3 versus 6.9 +/- 4.1 units/ml preoperatively, P less than 0.05) but thereafter returned to control levels at 1 month and remained so for more than 18 months. Postheparin DAO activity was similar in both groups with a maximum increase between 15 and 60 min following heparin administration. There was no correlation between maximal DAO activity and time since operation in the transplant group. Intestinal DAO activity was similar to unoperated animals 18 months after autotransplantation. These findings suggest that postheparin serum diamine oxidase activity is not influenced by autotransplantation and thus, is a potential marker of graft rejection following intestinal allotransplantation.     

Neuronal and astroglial injuries in patients undergoing coronary artery bypass grafting and aortic arch replacement during hypothermic cardiopulmonary bypass

More than 50% of patients suffer neuropsychologic impairment after cardiac surgery. We measured neuron-specific enolase (NSE) and S-100 protein (S-100) in patients' serum as putative markers of neuronal and astroglial cell injury, respectively. Group I (n = 13) underwent coronary artery bypass grafting (CABG) with mild hypothermic cardiopulmonary bypass (CPB); Group II (n = 6) underwent aortic arch replacement with deep hypothermic CPB; Group III (n = 8) underwent CABG under normothermia without CPB. During and after the operation, serum levels of NSE and S-100 were significantly increased only in Groups I and II (during CPB), NSE still being increased 12 h after surgery in Group II. This suggests that neuronal and astroglial cell injuries are more likely in patients undergoing CABG with mild hypothermic CPB or aortic arch replacement with deep hypothermic CPB than in those undergoing CABG under normothermia without CPB. However, these increases of NSE and S-100 failed to reflect clinical brain damage. Rather, an electroencephalogram, was only capable of detecting neurologic complications after surgery. Implications: Neuronal and astroglial cell injuries are likely to occur during coronary artery bypass grafting with mild hypothermic cardiopulmonary bypass (CPB) or aortic arch replacement with deep hypothermic CPB. Conversely, patients undergoing coronary artery bypass grafting without CPB under normothermic conditions may be less likely to suffer brain cell injury.     

Serum enzyme levels during intestinal ischemia.

Because the intestinal mucosa is most sensitive to ischemia, serum levels of mucosal enzymes, such as diamine oxidase, may be most likely to indicate intestinal ischemia. Our aim was to compare serum levels of mucosal (diamine oxidase, alkaline phosphatase) and seromuscular (creatinine phosphokinase, lactic dehydrogenase, serum glutamic oxaloacetic transminase) enzymes during intestinal ischemia of varying extent and duration in dogs. Group 1 (n = 6) underwent sham laparotomy. Group 2 (n = 8) had 50% of the small intestine devascularized. Group 3 (n = 8) had the superior mesenteric artery occluded for 2 hours and released. Group 4 (n = 8) had the superior mesenteric artery ligated. Serum samples were obtained before and 2, 4, 8, and 24 hours after operation, and histologic specimens were examined at 4 hours. Creatinine phosphokinase levels became elevated within 4 hours of ischemic injury in group 2 (223 +/- 197 vs. 68 +/- 26, p less than 0.05) and group 4 (212 +/- 136 vs. 76 +/- 29, p less than 0.05). Significant elevation of serum enzymes levels, except diamine oxidase, occurred in groups 2, 3, and 4 at 24 hours, including those with normal histology after temporary superior mesenteric artery occlusion. Thus seromuscular enzymes, particularly creatinine phosphokinase, were more likely to be elevated during intestinal ischemia. Enzyme levels were not influenced by the extent and reversibility of the ischemic injury.     

Continuous ultrafiltration attenuates the pulmonary injury that follows open heart surgery with cardiopulmonary bypass

BACKGROUND: Pulmonary injury after cardiac surgery is one of the complications of cardiopulmonary bypass. We evaluated the ultrafiltration technique in preventing and relieving the pulmonary injury that can follow open heart surgery with cardiopulmonary bypass (CPB). METHODS: Thirty patients with congenital heart defects were divided into two groups. In the control group conventional cardiopulmonary bypass was used without ultrafiltration. In the treated group, in addition to the same cardiopulmonary bypass procedure, balanced ultrafiltration plus modified ultrafiltration was used throughout cardiopulmonary bypass. Pulmonary function, hematocrit, serum albumin, and some inflammatory mediators were measured. RESULTS: Compared with measurements before anesthesia the pulmonary static compliance at 15 minutes and 6 hours post bypass had decreased by 27.8% and 34.0% in the control group versus 12.6% and 15.4% in the treated group, the airway resistance had increased by 38.0% and 45.2% in the control group versus 9.5% and 4.7% in the treated group, and the alveolar-arterial oxygen difference increased by 73.4% and 62.0% in the control group versus 52.1% and 35.9% in the treated group. Hemodilution from cardiopulmonary bypass caused the hematocrit and serum albumin to decrease by 35.8% and 32.8% in the control group versus 36.1% and 34.5% in the treated group at the termination of CPB. After 10 to 15 minutes modified ultrafiltration the hematocrit and serum albumin increased by 40.0% and 47.6%. At the termination of CPB the serum concentrations of interleukin-6, thromboxane B2, and endothelin-1 were increased by 160%, 265%, and 890% in the control group versus 103%, 208%, and 838% in the treated group compared with those before anesthesia. CONCLUSIONS: The combined use of balanced ultrafiltration and modified ultrafiltration can effectively concentrate the blood, modify the increase of some harmful inflammatory mediators, attenuate the lung edema and inflammatory pulmonary injury, and mitigate the impairment of pulmonary function.     

体外循环对大鼠肠黏膜屏障功能的影响

目的　观察大鼠体外循环(CPB)围术期肠黏膜通透性的变化以及对肠黏膜屏障功能的影响。方法　建立大鼠CPB模型,按照CPB后不同时间进行分组,分别采血测定血浆D-乳酸和脂多糖(LPS)的浓度并观察小肠组织病理变化。结果　CPB 1h后血浆D-乳酸和LPS开始升高,CPB结束后1h达到峰值,CPB后8h恢复正常。二者变化趋势一致,呈正相关(r=0. 8312 ,P <0 .0 5 ) ;CPB后小肠绒毛顶端上皮脱落,固有层白细胞聚集。结论　CPB术后早期肠黏膜屏障功能就已经受到损害,通透性增加。血浆D 乳酸浓度变化可用来判断肠黏膜屏障损伤程度,为CPB严重并发症的防治和预后评估提供有益的参考和实验依据     

Jejunal mucosal perfusion is well maintained during mild hypothermic cardiopulmonary bypass in humans

In the present study, the effects of mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB) on jejunal mucosal perfusion (JMP), gastric tonometry, splanchnic lactate, and oxygen extraction were studied in low-risk cardiac surgical patients (n = 10), anesthetized and managed according to clinical routine. JMP was assessed by endoluminal laser Doppler flowmetry. Patients were studied during seven 10-min measurement periods before, during, and 1 h after the end of CPB. Splanchnic oxygen extraction increased during hypothermia and particularly during rewarming and warm CPB. JMP increased during hypothermia (26%), rewarming (31%), and warm CPB (38%) and was higher 1 h after CPB (42%), compared with pre-CPB control. The gastric-arterial PCO(2) difference was slightly increased (range 0.04-2.26 kPa) during rewarming and warm CPB as well as 1 h after CPB, indicating a mismatch between gastric mucosal oxygen delivery and demand. None of the patients produced lactate during CPB. We conclude that jejunal mucosal perfusion appears well preserved during CPB and moderate (34 degrees C) hypothermia; this finding is in contrast to previous studies showing gastric mucosal hypoperfusion during CPB. Implications: Jejunal mucosal perfusion increases during mild hypothermic cardiopulmonary bypass (CPB). Intestinal laser Doppler flowmetry, gastric tonometry, and measurements of splanchnic lactate extraction could not reveal a local or global splanchnic ischemia during or after CPB. A mismatch between splanchnic oxygen delivery and demand was seen, particularly during rewarming and warm CPB.     

Mesenteric dysfunction after cardiopulmonary bypass: role of complement C5a

BACKGROUND: We investigated the effects of cardiopulmonary bypass (CPB) on ileal homeostasis, and the influence of functional inhibition of complement C5a on CPB-induced mesenteric injury. METHODS: Pigs were perfused on CPB for 1 hour and then perfused off CPB for an additional 2 hours. Antiporcine C5a monoclonal antibody (C5a MAb) was administered 20 minutes before onset of CPB to 6 pigs; 6 controls received saline vehicle. Total complement activity, ileal myeloperoxidase, and indices of ileal integrity were examined. RESULTS: Treatment with C5a MAb ameliorated CPB-induced abnormalities in endothelium-dependent relaxation to ADP and substance P, and the hypercontractile response to phenylephrine of ileal microvessels (88 to 168 microm). Ileal myeloperoxidase activity [units/g protein] was 41 +/- 11 in the C5a MAb group, compared to 83 +/- 13 in the saline group (19 +/- 10 base line). Total hemolytic complement activity was similar in the C5a MAb and saline groups (0.6 +/- 0.2 and 0.7 +/- 0.2 CH50 units). During CPB, ileal mucosal blood flow and mucosal pH, edema formation, and epithelial permeability deteriorated similarly in saline and C5a MAb groups. Inducible nitric oxide synthase (iNOS) mRNA expression was similar before and after CPB. CONCLUSIONS: CPB is associated with significant physiologic alterations in mucosal perfusion, epithelial permeability, edema formation, and blood flow regulation. Inhibition of C5a limits neutrophil-mediated impairment of ileal microvascular regulation after bypass, but does not improve extravascular mesenteric dysfunction after CPB.     

Influence of Methylprednisolone on Levels of Neuron-Specific Enolase in Cardiac Surgery: A Corticosteroid Derivative to Decrease Possible Neuronal Damage

Abstract   Background: Cerebral injury is a well-known complication after cardiac surgery with cardiopulmonary bypass (CPB), especially in adult patients. Specific biochemical markers like neuron-specific enolase (NSE) and S-100β protein were developed previously for early detecting neuronal damage after CPB. Corticosteroids are shown to reduce multisystemic deleterious effects of cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of this study is to demonstrate the decrease of serum neuron-specific enolase levels in patients who received corticosteroids before CPB. Methods: Thirty patients scheduled for elective coronary bypass surgery were included in the study. Patients were divided randomly into two groups as the control group (n = 15) who underwent a standard coronary bypass surgery without any additional medication and the study group (n = 15) who received 1 gm of methylprednisolone before CPB. Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation. Results : Serum cytokine and NSE levels were significantly increased after CPB above their normal range in both groups. In the study group, IL-6 and NSE levels were significantly reduced while IL-10 levels were much higher after CPB. High NSE levels significantly correlated with IL-6 levels in the control group. Conclusion: The lower levels of NSE in patients who received methylprednisolone may suggest that corticosteroids might be useful in decreasing possible neuronal damage during heart surgery. However, we were not able to demonstrate an adverse neurological outcome.     

Report of a substudy on warm versus cold cardiopulmonary bypass: changes in creatinine clearance.

BACKGROUND: Renal dysfunction remains a major complication of cardiac operations. There is concern regarding the possibility of increased renal injury during warm cardiopulmonary bypass (CPB). Therefore, we tested the hypothesis that warm CPB is associated with a greater reduction in creatinine clearance after cardiac surgery than hypothermic CPB. METHODS: We randomly assigned 300 patients who had elective coronary artery bypass grafting to warm (35.5 to 36.5 degrees C) or cold (28 degrees C to 30 degrees C) CPB. Preoperative and peak postoperative serum creatinine values were recorded. Creatinine clearance was estimated using the Cockroft Gault equation. Univariate and multivariable analyses were performed to test the association of CPB temperature and perioperative change in creatinine clearance. RESULTS: Demographic variables were similar between groups. Multivariable analysis did not confirm an association between temperature and change in creatinine clearance (p = 0.87). CONCLUSIONS: We did not confirm an association between warm CPB and increased renal dysfunction after cardiac operations compared with hypothermic CPB.     

A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open-heart surgery

Cerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a major source of morbidity. The effect of cardiopulmonary bypass temperature on cerebral function in terms of serum S100beta protein level and cerebral oxygenation monitored by near infrared spectroscopy (NIRO-300) in children is not known. In this study, 18 children undergoing open-heart surgery at the Hospital for Sick Children in London were equally assigned by minimisation to warm (35 +/- 1 degrees C) or cold (25 +/- 1 degrees C) CPB. Changes in S100beta protein and cerebral oxygenation were studied in both groups. S100beta protein serum level increased significantly after CPB in both groups. There was no significant difference in serum S100beta protein concentrations between the two groups. However, cerebral oxygenation in terms of tissue oxygen index (TOI) was significantly impaired during rewarming from cold CPB. Five patients were desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two in the warm patients. This study supports the use of warm CPB in children undergoing open-heart surgery, although further studies recruiting more patients are warranted.     

Serum S100 protein as a marker of cerebral damage during cardiac surgery

The identification of a serum marker to assist in the diagnosisof cerebral injury after cardiac surgery is potentially useful.S100 protein is an early marker of cerebral damage. It is releasedafter cardiac surgery performed under cardiopulmonary bypass(CPB). Its level is correlated with the duration of CPB, deepcirculatory arrest and aortic cross-clamping. Increased levelsof S100 protein are correlated with the age of the patient andthe number of microemboli, especially during aortic cannulation.Perioperative cerebral complications such as stroke, delayedawakening and confusion are associated with increased levelsof S100 protein directly after bypass and from 15 to 48 hafter it. In addition, increased levels of S100 protein arerelated to neuropsychological dysfunction after cardiac surgery.S100 protein has early and late release patterns after CPB;the early pattern may be due to sub-clinical brain injury. Thelate release pattern may be due to perioperative cerebral complications.Patients undergoing intracardiac operations combined with coronaryartery bypass surgery are more susceptible to brain injury andhave higher levels of S100 after CPB. Furthermore, adults andchildren undergoing deep circulatory arrest are more susceptibleto brain injury, in terms of higher S100 protein release afterCPB. Serum S100 protein levels are reduced after using arterialline filtration and covalent-bonded heparin to coat the innersurface of the CPB circuit. Br J Anaesth 2000; 85: 287–98     

Endothelial apoptosis is induced by serum of patients after cardiopulmonary bypass.

OBJECTIVE: Increased serum levels of a multitude of mediators like interleukins, tumor necrosis factor, elastase, adhesion molecules, and endotoxin have been described following cardiopulmonary bypass (CPB). The biological consequences of this complex response are unclear. METHODS: Serum samples of nine patients scheduled for elective coronary artery bypass grafting were obtained preoperatively and 1, 6, and 12 h after weaning from CPB. Additional serum samples were obtained perioperatively from four patients undergoing major lung resection and from four healthy volunteers. The apoptosis-inducing activity of serum samples on endothelial cells was examined using a tissue culture assay system. Endothelial cells were derived from human umbilical cords and incubated for 48 h with serum samples in various dilutions during their second passage. The culture plates were fixed with methanol/acetone and stained with the DNA dye diamidinophenylindole. Apoptotic and normal cells were identified and counted using phase contrast and fluorescence microscopy. RESULTS: The proportion of apoptotic endothelial cells was 5.6-fold higher in culture plates incubated with diluted (30%) serum samples obtained at 6 h after weaning from CPB when compared to plates incubated with preoperative samples (P=0.0077). A smaller effect occurred already at 1 h in some patients, whereas at 12 h after weaning from CPB no increased endothelial apoptosis was observed. No proapoptotic activity was found in preoperative as well as in control samples from patients undergoing lung resection or from healthy volunteers. CONCLUSIONS: Serum of patients after CPB exerts a strong apoptosis inducing activity on human endothelial cells. Apoptotic death of endothelial cells following CPB may be responsible for postoperative vascular and bypass dysfunction including phenomena like increased capillary permeability.     

Cerebral production of adrenomedullin afer hypothermic cardiopulmonary bypass in adult cardiac surgical patients.

Adrenomedullin is a potent vasodilatory peptide originally identified in human pheochromocytoma. Plasma adrenomedullin increases during and after cardiopulmonary bypass (CPB). However, the site at which production of adrenomedullin is augmented has not been identified. In the present study, we examined the contribution of the cerebral vasculature to the production of adrenomedullin in patients before, during, and after CPB. Ten patients undergoing coronary artery bypass grafting with mild hypothermic CPB were studied. Cerebral blood flow was measured using the Kety-Schmidt method before, during, and after CPB. Plasma adrenomedullin concentrations from radial artery and internal jugular bulb blood were measured by radioimmunoassay, and cerebral adrenomedullin production was evaluated. Adrenomedullin production in the cerebral vasculature was significantly enhanced after CPB and correlated with aortic cross-clamping time. The cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after CPB. IMPLICATIONS: Plasma adrenomedullin has been reported to increase in humans after cardiac surgery involving cardiopulmonary bypass. In this study, we demonstrated that cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after cardiopulmonary bypass.     

婴幼儿先天性心脏病体外循环前后丙二醛的变化及意义

目的研究婴幼儿心脏手术CPB前后丙二醛（MDA）的改变及其意义。方法30例室间隔缺损（VSD）患儿，按有无肺动脉高压（pH）分为无pH组（A组）15例，pH组（B组）15例。于CPB前和CPB结束后0,1，3，24h分别抽取桡动脉血3ml，测定血清MDA和cTnI的浓度变化。结果两组患儿血清MDA和cTnI浓度均于CPB后明显升高（P〈0．01）；在CPB后，B组血清MDA和cTnI浓度高于A组（P〈O．01）；B组血清cTnI和MDA浓度呈显著正相关（氏0．01）。结论先心伴pH患儿CPB后血清MDA和cTnI浓度明显高于先心不伴pH的患儿。氧自由基在CPB后心肌缺廓再灌注损伤中起重要作用。     

Analysis of intestinal microvascular permeability associated with cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a generalized inflammatory response and splanchnic edema formation that are thought to be related to microvascular barrier injury. In particular, intestinal edema and dysfunction have been associated with sepsis and post-CPB complications. The purpose of this study was to measure the forces determining fluid flux induced by CPB across the intestinal microvascular barrier. MATERIALS AND METHODS: An anesthetized canine model was used for this study (n = 12). To determine mesenteric microvascular permeability, a mesenteric lymphatic was cannulated and mesenteric venous pressure was elevated to 33 +/- 1 mm Hg to reach a minimal lymph protein concentration (CL). With simultaneous measurement of plasma protein concentrations (CP), the reflection coefficient, sigma, was calculated using the formula: sigma = 1 - CL/CP. Capillary pressures (PC), lymph flow (QL), lymph protein flux, transvascular protein flux, and intestinal tissue water were all measured using standard techniques. Normothermic cardiopulmonary bypass with flows of 75-80 ml/kg/min was initiated after a steady state was achieved, and CPB was continued for 2 h and then discontinued. Measurements were repeated 30 min after CPB was discontinued. A second group (n = 5) was studied without mesenteric venous pressure elevation to evaluate the role of capillary pressure on the increased fluid flux seen with the initiation of CPB. RESULTS: Initiation of CPB was associated with an increase in intestinal microvascular permeability. Sigma decreased from 0.77 +/- 0.01 to 0.68 +/- 0.01 (P < 0.05) with the initiation of CPB. This corresponded with statistically significant increases in both transvascular protein flux from 310 +/- 22 to 465 +/- 39 ml/min at 30 min and intestinal tissue water from 82.8 +/- 0.7 to 84.3 +/- 0.5% after weaning from CPB. Capillary pressure did not significantly increase with the initiation of CPB. CONCLUSIONS: Initiation of CPB results in a moderate increase in intestinal microvascular permeability to protein and an increase in intestinal tissue water. The increases in tissue water are not due to increased capillary pressure. A better understanding of the microvascular changes associated with extracorporeal circulation will facilitate the search for clinical interventions to minimize the impact of CPB.