心肺复苏后脑缺血再灌注损伤治疗理念及相关动物模型研究进展

心肺复苏后脑缺血再灌注损伤是一个复杂的病理生理变化过程,由多种损伤机制共同参与。自心肺复苏后系统性综合治疗和亚低温治疗在临床上广泛应用后,目前已有多种治疗理念在不同的动物实验和动物模型基础上被提出,包括缺血预处理、药物预处理、缺血后处理、和药物后处理,而后吸入麻醉药对心肺复苏后脑缺血再灌注损伤的保护作用受到了人们的重视,而七氟烷后处理已经成为目前研究的热点之一。为了指导临床上的心肺复苏,人们一直在利用不同动物模型,探究不同保护方法,寻找有效的脑保护药物。而各种治疗理念的提出均是建立在动物实验和动物模型的基础上,窒息性心肺复苏模型模拟围术期气道梗阻,能较贴切的复制临床上由窒息引起的心肺复苏后脑损伤,对将来指导临床复苏具有重大意义。     

The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA‐mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3–6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA‐mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3‐methyladenine (3‐MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3‐MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA‐mediated lung injury.     

体外循环心脏手术围术期脑损伤监测进展

脑损伤是体外循环心脏手术的严重并发症之一,目前患病人数在全球范围内呈逐年增高的趋势,并且临床上应用的脑保护措施效果并不确切,因此有效的神经系统监测关系到外科手术的成败和病人的预后。本文从术中脑组织氧供需平衡、栓子的监测、生化标志物和术后神经功能监测四个方面综述目前脑损伤监测的新进展。     

近红外分光仪在小儿体外循环中的应用

目的探讨小儿体外循环中,近红外分光仪(NIRS)在监测脑氧合功能方面的价值。方法心内直视手术病人24例,随机平均分为两组:中度低温体外循环(MHCPB)组(n=12)和深低温停循环(DHCA)组(n=12),NIRS连续监测脑组织氧合血红蛋白(cere-HbO2),CPB开始、降温末、复温末以及术后6小时四个时点分别测定颈静脉球血测定乳酸值(Lact)和特异性神经源性烯醇化酶(NSE),术前、术后脑电图(EEG)检查各一次,并进行相关分析。结果MHCPB组中,无脑电图异常,cere-HbO2指标变化不大,与生化指标也无显著相关;DHCA组中,两例患儿术后出现异常脑电图,cere-HbO2指标在停循环开始便显著下降,下降幅度和持续时间与复温末Lact及NSE值显著相关。结论DHCA中,cere-HbO2与反映脑损害的其它指标显著相关,NIRS是一种崭新的,无创的脑氧合监测方法。     

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

Objective

Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.

Methods

Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.

Results

The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.

Conclusions

HLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.     

Translocation of S100A1(1) calcium binding protein during heart surgery

Myocardial ischemia during cardiopulmonary bypass terminated by reperfusion generally leads to different degrees of damage of the cardiomyocytes induced by transient cytosolic Ca(2+) overload. Recently, much attention has been paid to the role of heart-specific Ca(2+)-binding proteins in the pathogenesis of myocardial ischemia-reperfusion injury. S100A1 is a heart-specific EF-hand Ca(2+)-binding protein that is directly involved in a variety of Ca(2+)-mediated functions in myocytes. The aim of our study was to investigate the localization and translocation of S100A1 in the human heart under normal (baseline) conditions and after prolonged ischemia and reperfusion of the myocardium. Our data suggest that S100A1 is directly involved in the transient perioperative myocardial damage caused by ischemia during open heart surgery in humans. Given its role in the contractile function of muscle cells, this S100 protein could be an important "intracellular link" in ischemia-reperfusion injury of the heart.     

Blood phagocyte activation during open heart surgery with cardiopulmonary bypass

Open heart surgery with a cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response which significantly contributes to adverse postoperative complications. The purpose of this study was to characterize the activation of blood phagocytes during open heart surgery with CPB. Blood samples were collected during and up to 24 h after surgery. The production of reactive oxygen species (ROS) in whole blood, the expression of surface molecules by blood phagocytes and complement activity in the plasma were determined. A cDNA microarray analysis of leukocyte RNA profile of genes was performed related to the inflammatory response. Activation of the complement was already observed at the beginning of CPB. This was followed by an increase in the neutrophil number and in both spontaneous and opsonized zymosan-activated ROS production after the onset of reperfusion. The activation of blood phagocytes was affirmed by changes in surface receptors involved in the adhesion and migration of leukocytes (CD11b, CD62L and CD31). Gene arrays also confirmed the activation of leukocytes 4 h after reperfusion. In conclusion, open heart surgery with a cardiopulmonary bypass was found to be associated with a rapid and pronounced activation of blood phagocytes and complement activation which was partly independent at the onset of CPB.     

平衡超滤技术对小儿先心病术后炎症因子、凝血功能及肺功能的影响

目的:探讨平衡超滤技术对小儿先心病术后炎症因子、凝血功能及肺功能的影响。方法:选择2014年9月至2017年9月我院接诊的100例先天性心脏病患儿进行研究,通过随机数表法分为观察组55例和对照组45例,两组均于体外循环下实施心内直视手术,观察组在体外循环启动后患儿复温时开始平衡超滤,并于体外循环结束后即刻进行改良超滤,对照组仅在体外循环结束后即刻进行改良超滤。比较两组不同时间点炎症因子、凝血功能及肺功能的变化、术后恢复情况及并发症。结果:于体外循环结束后(术后)20 min(T1)、术后2 h(T2)、术后6 h(T3)各时点,观察组血清肿瘤坏死因子(TNF)-α、白介素(IL)-6、IL-10均明显比对照组低(P<0.05);观察组各时点活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)均明显低于对照组(P<0.05);观察组各时点肺静脉顺应性(Cstat)、氧合指数(OI)在各时点均明显高于对照组,肺泡-动脉氧分压梯度(AaDO2)明显低于对照组(P<0.05);观察组血管活性药使用时间、呼吸机使用时间和ICU住院时间均明显比对照组短(P<0.05),观察组感染、弥散性血管性凝血、肺功能损伤等发生率明显低于对照组(P<0.05)。结论:在改良超滤技术上,联合平衡超滤更有助于减轻小儿先心病术后炎症因子的释放,具有较好的凝血功能、肺功能保护作用,可有效促进术后恢复,减少围术期并发症。     

Development of post-pump syndrome in a sheep after mitral valve stenting

A one-year-old healthy sheep received an implant stenting the mural ('posterior') leaflet of the mitral valve. The experiment was authorized by the Cantonal Ethical Committee. The surgery was performed on the open, beating heart during cardiopulmonary bypass (CPB). Management of anaesthesia was based on isoflurane with mechanical intermittent positive pressure ventilation (IPPV) of the lungs, combined with intercostal nerve blocks and intravenous fentanyl and lidocaine. Marked cardiovascular depression occurred towards the end of CPB time and required high doses of dopamine, dobutamine, lidocaine and ephedrine to allow for weaning off the CPB pump. Moreover, severe pulmonary dysfunction developed when IPPV was re-initiated after CPB. Hypoxaemia persisted throughout the recovery from general anaesthesia. Multiple organ failure developed gradually during the three postoperative days, leading to euthanasia of the animal. As described in this case, marked lung injury associated with some degree of failure of other vital organs may occur in sheep after CPB. Intraoperative cardiorespiratory complications when weaning-off may indicate the development of 'post-pump syndrome'.     

Granulocyte Colony Stimulating Factor Reduces Brain Injury in a Cardiopulmonary Bypass-Circulatory Arrest Model of Ischemia in a Newborn Piglet

Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18 °C, subjected to 60 min of DHCA, re-warmed and recovered for 8–9 h. At the end of experiment, the brains were perfused, fixed and cut into 10 µm transverse sections. Apoptotic cells were visualized by in situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm². The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46 ± 0.37 to 3.67 ± 1.57 (p = 0.002); in the CA1, from 0.11 ± 0.19 to 5.16 ± 1.57 (p = 0.001), and in the CA3, from 0.28 ± 0.25 to 2.98 ± 1.82 (p = 0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51 and 37 %, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA.     

Cognitive dysfunction after cardiac surgery: Pathophysiological mechanisms and preventive strategies

Despite improvements in surgical techniques and the implementation of effective brain protection strategies, the incidence of brain injury after cardiac surgery has remained relatively constant over the years as patients have become older and sicker. Cognitive dysfunction is the most common clinical manifestation of brain injury after cardiac surgery. Its occurrence is related to a combination of three factors that are often associated with cardiopulmonary bypass (CPB): embolism, hypoperfusion, and the inflammatory response. However, such factors and their potential cerebral consequences are not exclusive to CPB. Postoperative cognitive dysfunction also afflicts patients who undergo cardiac surgery without CPB as well as nonsurgery patients who undergo transcatheter interventions. There is growing evidence that patient-related factors such as the presence of (cerebro)vascular risk factors play an important role in both early and late postoperative cognitive dysfunction.     

Preexercise carbohydrate ingestion, glucose kinetics, and muscle glycogen use: effect of the glycemic index.

Eight trained men cycled at 70% peak oxygen uptake for 120 min followed by a 30-min performance cycle after ingesting either a high-glycemic index (HGI), low-glycemic index (LGI), or placebo (Con) meal 30 min before exercise. Ingestion of HGI resulted in an elevated (P<0.01) blood glucose concentration compared with LGI and Con. At the onset of exercise, blood glucose fell (P<0.05) such that it was lower (P<0.05) in HGI compared with LGI and Con at 15 and 30 min during exercise. Plasma insulin concentration was higher (P<0.01) throughout the rest period after ingestion of HGI compared with LGI and Con. Plasma free fatty acid concentrations were lower (P<0.05) throughout exercise in HGI compared with LGI and Con. The rates of [6,6-(2)H]glucose appearance and disappearance were higher (P<0.05) at rest after ingestion and throughout exercise in HGI compared with LGI and Con. Carbohydrate oxidation was higher (P<0.05) throughout exercise, whereas glycogen use tended (P = 0.07) to be higher in HGI compared with LGI and Con. No differences were observed in work output during the performance cycle when comparing the three trials. These results demonstrate that preexercise carbohydrate feeding with a HGI, but not a LGI, meal augments carbohydrate utilization during exercise but does not effect exercise performance.     

Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury

Endogenous CO, a product of heme oxygenase activity, has vasodilator and cytoprotective effects in the cerebral circulation of newborn pigs. CO-releasing molecule (CORM)-A1 (sodium boranocarbonate) is a novel, water-soluble, CO-releasing compound. We addressed the hypotheses that CORM-A1 1) can deliver CO to the brain and exert effects of CO on the cerebral microvasculature and 2) is cerebroprotective. Acute and delayed effects of topically and systemically administered CORM-A1 on cerebrovascular and systemic circulatory parameters were determined in anesthetized newborn pigs with implanted closed cranial windows. Topical application of CORM-A1 (10(-7)-10(-5) M) to the brain produced concentration-dependent CO release and pial arteriolar dilation. Systemically administered CORM-A1 (2 mg/kg ip or iv) caused pial arteriolar dilation and increased cortical cerebrospinal fluid CO concentration. Systemic CORM-A1 did not have acute or delayed effects on blood pressure, heart rate, or blood gases. Potential cerebroprotective vascular effects of CORM-A1 (2 mg/kg ip, 30 min before seizures) were tested 2 days after bicuculline-induced epileptic seizures (late postictal period). In control piglets, seizures reduced postictal cerebrovascular responsiveness to selective physiologically relevant vasodilators (bradykinin, hemin, and isoproterenol) indicative of cerebrovascular injury. In contrast, in CORM-A1-pretreated animals, no loss of postictal cerebrovascular reactivity was observed. We conclude that systemically administered CORM-A1 delivers CO to the brain, elicits the vasodilator and cytoprotective effects of CO in the cerebral circulation, and protects the neonatal brain from cerebrovascular injury caused by epileptic seizures.     

Metabolic functions of the lung and systemic vasoregulation

Several important vasoactive substances are taken up and/or metabolized during a single transpulmonary passage. Such substances include 5-hydroxytryptamine, prostaglandins (PGs) of the E and F series, and peptide substrates (angiotensin I and bradykinin) for angiotensin-converting enzyme (ACE). When these metabolic processes are altered, predictable changes in systemic hemodynamics can follow because of altered arterial concentrations of the vasoactive substances. For example, a single dose of captopril (2 mg/kg, i.v.) given to conscious rabbits caused prolonged depression in pulmonary ACE activity, an effect that coincided with a significant reduction in mean systemic arterial pressure. In another study, total cardiopulmonary bypass in anesthetized dogs was associated with a time-dependent increase in arterial levels of immunoreactive PGE. Coincident with this elevation in PGE was a significant decrease in total systemic vascular resistance. The decrease in resistance was inhibited by pretreatment with indomethacin or by maintaining lung perfusion during extracorporeal circulation (i.e., left heart bypass). Thus, in the intact animal, significant reduction in lung metabolism, induced by either pharmacological or other experimental means, may modify vasoregulation of peripheral circulation. Furthermore, measurement of these metabolic functions may provide biochemical information about the pulmonary microcirculation, which is both the locus of these activities and an early site of acute lung injury.     

Thematic Review Series: Calorie Restriction and Ketogenic Diets: The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury

The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans.     

Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer’s Disease

Alzheimer’s disease is the most frequent type of dementia and diagnosed late in the progression of the illness when irreversible brain tissue loss has already occurred. For this reason, treatments have been ineffective. It is imperative to find novel therapies ameliorating modifiable risk factors (hypertension, stroke, diabetes, chronic kidney disease, and traumatic brain injury) and effective against early pathogenic mechanisms including alterations in cerebral blood flow leading to poor oxygenation and decreased access to nutrients, impaired glucose metabolism, chronic inflammation, and glutamate excitotoxicity. Angiotensin II receptor blockers (ARBs) fulfill these requirements. ARBs are directly neuroprotective against early injury factors in neuronal, astrocyte, microglia, and cerebrovascular endothelial cell cultures. ARBs protect cerebral blood flow and reduce injury to the blood brain barrier and neurological and cognitive loss in animal models of brain ischemia, traumatic brain injury, and Alzheimer’s disease. These compounds are clinically effective against major risk factors for Alzheimer’s disease: hypertension, stroke, chronic kidney disease, diabetes and metabolic syndrome, and ameliorate age-dependent cognitive loss. Controlled studies on hypertensive patients, open trials, case reports, and database meta-analysis indicate significant therapeutic effects of ARBs in Alzheimer’s disease. ARBs are safe compounds, widely used to treat cardiovascular and metabolic disorders in humans, and although they reduce hypertension, they do not affect blood pressure in normotensive individuals. Overall, there is sufficient evidence to consider long-term controlled clinical studies with ARBs in patients suffering from established risk factors, in patients with early cognitive loss, or in normal individuals when reliable biomarkers of Alzheimer’s disease risk are identified.     

Metabolic cardioprotection by pyruvate: recent progress

Pyruvate, a natural metabolic fuel and antioxidant in myocardium and other tissues, exerts a variety of cardioprotective actions when provided at supraphysiological concentrations. Pyruvate increases cardiac contractile performance and myocardial energy state, bolsters endogenous antioxidant systems, and protects myocardium from ischemia-reperfusion injury and oxidant stress. This article reviews and discusses basic and clinically oriented research conducted over the last several years that has yielded fundamental information on pyruvate's inotropic and cardioprotective mechanisms. Particular attention is placed on pyruvate's enhancement of sarcoplasmic reticular Ca2+ transport, its antioxidant properties, and its ability to mitigate reversible and irreversible myocardial injury. These research efforts are establishing the essential foundation for clinical application of pyruvate therapy in numerous settings including cardiopulmonary bypass surgery, cardiopulmonary resuscitation, myocardial stunning, and cardiac failure.     

Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass

The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.     

Fetal monitoring during maternal cardiac surgery with cardiopulmonary bypass.

Fetal cardiac activity was monitored with an external ultrasound transducer in two patients with clinical class III heart disease due to severe mitral stenosis complicated by pulmonary hypertension, undergoing open heart surgery with cardiopulmonary bypass in the 2nd trimester of pregnancy. Fetal distress was detected in one patient, who had mitral valvuloplasty, and was corrected by increasing the rate of blood flow, and the other patient had a mitral valve replacement but no fetal distress was noted. The postoperative course of both mothers and fetuses was uneventful.     

Inflammatory cytokines and soluble receptors after coronary artery bypass grafting

Much interest has been focused on the overexpression of proinflammatory cytokines, but studies on their soluble receptors are rare. For a comprehensive picture of cytokine activation in cardiac surgery, a combination of cytokines and the corresponding soluble receptor concentration should be determined. Blood samples were collected from the radial artery and coronary sinus perioperatively in ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. TNF-alpha, IL-6, sTNFRI, sTNFRII, and sIL-6R levels in the plasma were determined. Systemic TNFRI, TNFRII and IL-6 increased significantly after reperfusion to the myocardium, while perioperative systemic sIL-6r levels were similar. Arterial and sinus levels of TNFRI, TNFRII and sIL-6r were similar before cardiopulmonary bypass. Five minutes after reperfusion to the myocardium, higher sinus TNFRI and TNFRII and lower sinus sIL-6R levels were observed as compared to the arterial levels. The myocardium release of sTNFRI (r=0.57, P=0.089) and sTNFRII (r=0.64, P=0.047) positively correlated with the change of cardiac index after cardiopulmonary bypass. Myocardium releases sTNFRI and sTNFRII after ischaemic-reperfusion injury, and this may be of benefit to cardiac performance. sIL-6R is constantly being produced in areas other than the myocardium, while sIL-6R levels are reduced by consumption in the myocardium after ischaemic-reperfusion injury.