Cardiopulmonary Bypass Process Research Articles

Cardiopulmonary Bypass and Perioperative Mechanical Ventilation Strategy: National Turkey Study

Objective: This study aims to describe anesthesiologists' perioperative mechanical ventilation strategies in cases where cardiopulmonary bypass (CPB) is performed in Turkey. Material and Methods: Survey questions were sent twice via e-mail to members of the two associations consisting of specialists in Anesthesiology and Reanimation. The questions were divided into three parts to determine anesthesia applications and mechanical ventilation strategies in the preoperative, intraoperative, and postoperative periods of CPB. Results: The questionnaire was provided with the participation of 269 anesthesiologists. 105 (40.2%) participants stated that the number of intensive care unit beds in their hospital was over 20. A 6 ml/kg (42.5%) coefficient is preferred in calculating tidal volume outside the CPB process. The number of participants who preferred low (0-5 cmH2O) positive end-expiratory pressure (PEEP) throughout the surgery was 41.1%. 40.8% of the participants prefer 5-10 cmH2O PEEP in “hemodynamically stable and obese patients”. During the CPB process, 38.3% of the participants turned off the mechanical ventilator, and 24.4 % preferred to wean the patient from the mechanical ventilator. While 35.8 % of anesthesia specialists preferred recruitment maneuvers, 38.9% did not. It was concluded that 51% of the participants preferred non-invasive ventilation in patients with hypoxemia/hypercapnia, and 55.1% applied pulmonary rehabilitation after extubation to all patients. Conclusion: Our study showed that the mechanical ventilation strategies followed by most anesthesiologists in CPB in Turkey are similar.

Nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor alpha protein (TNF-α), heme oxygenase-1 (HO-1) gene expressions during cardiopulmonary bypass

During extracorporeal circulation, blood is in contact with nonendothelial surfaces. The increase in the amount of blood touching the non-endothelial surface increases the damage to the blood elements. This initiates and increases oxidative stress. Increased oxidative stress leads to the activation of antioxidant systems. These two systems work gradually in the process of Cardiopulmonary Bypass. This study aims to investigate the changes of TNF-α, Nrf2 and HO-1 gene expression in extracorporeal circulation. Fifteen patients who underwent open heart surgery were included in the study. Blood samples were taken preoperatively, during cardiopulmonary bypass (CPB) and 24 hours postoperatively. TNF-α, Nrf2 and HO-1 gene expressions in plasma samples were studied by using appropriate kits. Changes in gene expressions were compared. TNF-α gene expression increased during CPB compared to preoperative levels (p <0.05). Similarly, Nrf-2 gene expression increased significantly during CPB (p <0.001) and decreased postoperatively (p <0.001). There was a significant increase in HO-1 gene expression during CPB (p <0.01). Postoperatively, this increase was found to decrease similar to Nrf2 (p <0.05). According to the results, TNF-α, Nrf2, HO-1 gene expressions increase during CPB and these values decrease after the operation. This shows that oxidative stress and inflammatory processes start with CPB and antioxidant processes start similarly. With the termination of CPB, both processes are terminated. This has been demonstrated by gene expressions. Future studies will make it easier to understand these processes.

Dexmedetomidine Ameliorates Post-CPB Lung Injury in Rats by Activating the PI3K/Akt Pathway

Purpose: To investigate the protective effects of dexmedetomidine (Dex) on post cardiopulmonary bypass (CPB) lung injury in rats and to explore the possibility of underlying mechanisms involving phosphatidylinositol 3-kinase (PI3K)/Akt. Materials and Methods: Forty healthy male Sprague–Dawley rats were randomly divided into five groups (n = 8 for each). A left lung ischemia-reperfusion injury model of CPB was established in all five groups. Rats were given saline, dexmedetomidine (Dex), dimethyl sulfoxide (DMSO), wortmannin (Wtm), and Dex plus Wtm during the CPB process, in Group Saline, Dex, DMSO, Wtm, and Dex + Wtm, respectively. Mean arterial pressure, oxygenation index (OI), and respiratory index (RI) were measured at the following three timepoints: before CPB (T1), at the onset of opening of the left hilus pulmonis (T2), and at the end of the CPB process (T3). At T3, hematoxylin and eosin (H&E) staining was conducted to evaluate pathology of lung injury. The rate of lung tissue apoptosis was determined by flow-cytometry. The expression of Akt, p-Akt, caspase-3, and caspase-9 was assessed by Western blot. Results: Dex treatment during CPB protected rat lungs from post-CPB lung injury, manifested by improved lung function, mitigated pathological damage, and reduced lung tissue apoptosis. The expression and phosphorylation of Akt was significantly enhanced by Dex treatment compared to the saline/DMSO-treated group. Wtm, a recognized PI3K inhibitor, abolished the protective effect of Dex. The levels of caspase-3 and caspase-9 were also significantly elevated in the Wtm-treated group. Conclusions: Dex reduces post-CPB lung injury in rats, at least partially, by activating the PI3K/Akt pathway and inhibiting lung tissue apoptosis.

A novel augmented venous-drainage model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.

Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are commonly used in cardiac surgery. However, the mortality and morbidity are still high in practice. Developing novel protective stategies and elucidating the underlying mechanisms for the pathophysiological consequences of DHCA have been hampered because of the absence of a satisfactory recovery animal model. The aim of this study was to establish a novel and safe DHCA model without blood priming in rats to study the pathophysiology of potential complications. Ten adult male Sprague-Dawley rats (age, 14-16 weeks; weight, 200-300g) were used. The entire CPB circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a home-made heat exchanger, all of which were connected via silicon tubing. The volume of the priming solution was less than 10 ml. The right jugular vein, right carotid artery and left femoral artery were cannulated. The blood was drained from the right atrium through the right jugular vein and fed back to the rat via the left femoral artery. CPB was commenced at a full flow rate. The animals were cooled to a pericranial temperature of 18°C and then subjected to 45 minutes of DHCA with global ischemia. Circulatory arrest was followed by rewarming and over 60 minutes of reperfusion. CPB was terminated carefully. Blood in the circuit was centrifuged and slowly transfused to achieve optimal hematocrit. Blood gas and hemodynamic parameters were recorded at each time point before CPB, during CPB and after CPB. All CPB and DHCA processes were achieved successfully. No rat died in our research. Blood gas analyses at different times were normal. Cardiac function and blood pressure were stable after the operation. The vital signs of all the rats were stable. The novel augmented venous-drainage CPB and DHCA model in rats could be established successfully without blood priming.

Comparison of current practices of cardiopulmonary perfusion technology in Iran with American Society of Extracorporeal Technology's standards.

Introduction: Standards have a significant role in showing the minimum level of optimal optimum and the expected performance. Since the perfusion technology staffs play an the leading role in providing the quality services to the patients undergoing open heart surgery with cardiopulmonary bypass machine, this study aimed to assess the standards on how Iranian perfusion technology staffs evaluate and manage the patients during the cardiopulmonary bypass process and compare their practice with the recommended standards by American Society of Extracorporeal Technology. Methods: In this descriptive study, data was collected from 48 Iranian public hospitals and educational health centers through a researcher-created questionnaire. The data collection questionnaire assessed the standards which are recommended by American Society of Extracorporeal Technology. Results: Findings showed that appropriate measurements were carried out by the perfusion technology staffs to prevent the hemodilution and avoid the blood transfusion and unnecessary blood products, determine the initial dose of heparin based on one of the proposed methods, monitor the anticoagulants based on ACT measurement, and determine the additional doses of heparin during the cardiopulmonary bypass based on ACT or protamine titration. It was done only in 4.2% of hospitals and health centers. Conclusion: Current practices of cardiopulmonary perfusion technology in Iran are inappropriate based on the standards of American Society of Cardiovascular Perfusion. This represents the necessity of authorities’ attention to the validation programs and development of the caring standards on one hand and continuous assessment of using these standards on the other hand.

Effects of Sevoflurane Inhalation During Cardiopulmonary Bypass on Pediatric Patients: A Randomized Controlled Clinical Trial.

The effects of sevoflurane inhalation during cardiopulmonary bypass (CPB) on postoperative courses and serum cardiac troponin I (cTnI) concentrations in pediatric patients undergoing cardiac surgery have not been extensively investigated. In this single-center, prospective, randomized trial, an anesthetic regimen containing 2% sevoflurane used throughout the CPB process was compared with a total intravenous anesthesia (TIVA) regimen. One hundred and three patients undergoing congenital heart defect repair with CPB were included in this prospective randomized controlled study. They were randomized into two groups: the sevoflurane group, who received 2% sevoflurane during CPB via an oxygenator, and the control group, who received only an oxygen-air mixture. The pre- and intra-operative parameters were comparable between the two groups. There was a slight but significant increase of arterial diastolic pressure in the sevoflurane group immediately after CPB compared with control patients (46.9 ± 9.3 mm Hg vs. 43.6 ± 8.9 mm Hg; p = 0.033). There was no death in either group. The postoperative ventilation time (in mean [95% confidence interval]) was shorter in the sevoflurane group than that in the control group (26.1 [19.2, 33.0] h vs. 37.7 [24.4, 50.9] h; p = 0.014). The postoperative ICU time, hospital days, and serial serum cTnI concentrations were not significantly different between the two groups. Inhalation of 2% sevoflurane during CPB is beneficial to the recovery of pediatric patients undergoing cardiac surgery but has no significant effect on postoperative cTnI release.

The Protective Effects of Sufentanil Pretreatment on Rat Brains under the State of Cardiopulmonary Bypass.

This study aimed to observe the protective effects of sufentanil pretreatment on rat cerebral injury during cardiopulmonary bypass (CPB) and to explore the underlying mechanism. Twenty-four male adult Sprague Dawley (SD) rats were divided into 4 groups. Then, the rat CPB model was established. A 14G trocar was inserted into the atrium dextrum. For rats in S1 and S5 groups, sufentanil (1 µgKg(-1) and 5 µgKg(-1)) were applied before CPB process. After the operation, rat brain samples were harvested for measurement of the water content of the brains, total calcium in brain tissue and the level of serum S100β. Compared with the Sham group, the water content and the total calcium of the brain tissue, and the expression of S100β in serum were significantly increased in the CPB group (P<0.05). Compared with the CPB group, sufentanil treatment significantly reduced the water content of the brains, the total calcium and S100β expression (P<0.05). The blood pressure and heart rate were significantly decreased in groups CPB, S1, and S5 compared with Sham group during CPB. Compared with the Sham group, the levels of pH and blood lactate in other groups were decreased and increased, respectively, in the post-CPB period. During the CPB and post-CPB periods, the hematocrit levels were significantly down-regulated in groups CPB, S1, and S5 compared with Sham group. In conclusion, sufentanil pretreatment was effective in reducing the cerebral injury during CPB. Reduction in calcium overload may be a potential mechanism in such process.

Targeting cefuroxime plasma concentrations during coronary artery bypass graft surgery with cardiopulmonary bypass.

Patients are at risk for severe postoperative infections after coronary artery bypass graft (CABG) surgery. Clinical laboratory data showed that unbound plasma concentrations of cefuroxime were not always adequate, therefore we developed a new dosing regimen. The aim of this prospective study is to evaluate the new dosing strategy by monitoring patients for unbound cefuroxime plasma concentrations during CABG surgery with cardiopulmonary bypass (CPB). A Dutch teaching hospital. In this prospective trial, patients scheduled for CABG surgery with CPB were included. A starting dose of 1500 mg cefuroxime was given with anesthesia induction, followed by 750 mg cefuroxime every hour until wound closure. In case of renal failure the dosing regimen was adapted. Serial blood samples were collected before, during and after the CPB process. Pharmacokinetic modelling was performed by using an 'iterative two-stage Bayesian population procedure'. Unbound plasma concentrations of cefuroxime. 22 patients were included, data could be evaluated of 21 patients. In 24 % of the patients the unbound cefuroxime plasma concentration was below the target range during surgery before CPB started. Patients with a bodyweight above 100 kg or age <60 years were more likely to have unbound plasma concentrations below the target range (P = 0.030 and P = 0.008). During CPB, the half-life of unbound cefuroxime increased by 17 % and the clearance decreased by 11 % compared to before CPB (P = 0.033 and P = 0.014). The mean pharmacokinetic parameters before, during and after CPB were as follows: elimination half-life 72, 84 and 76 min; clearance of unbound cefuroxime (Clu) 14.2, 12.7, 13.8 l/h and volume of distribution (Vu) 0.280, 0.284 and 0.290 l/kg respectively. Variations in unbound fractions before, during and after CPB were below 2 %, implicating the unbound fraction of cefuroxime is not influenced by CPB. Our results show that CPB during CABG surgery does not lead to inadequate unbound cefuroxime concentrations. Age, renal function and possibly also weight are more important factors that can result in unbound plasma cefuroxime concentrations below the target value.

A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming.

Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming. Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n = 10) and control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. The volume of the priming solution, composed of 6% HES 130/0.4 and 125 IU heparin, was less than 12 ml. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rat of 100-120 ml × kg (-1)× min(-1) in CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg. All CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable. The establishment of CPB without blood priming in rats can be achieved successfully. The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

Establishment of a novel rat model without blood priming during normothermic cardiopulmonary bypass

An effective animal model was needed for research on the pathophysiology of cardiopulmonary bypass (CPB). Rat models were considered suitable for research into CPB, recently. The aim of the article is to establish a simple and safe CPB model without blood priming in rats, containing the advantages of controlling temperature precisely, being similar to the clinical process and laying the foundation for the further study of a deep hypothermic circulatory arrest (DHCA) model. Ten Sprague-Dawley rats, divided into a CPB group (n=7) and a sham group (n=3), received sevoflurane inhalation anesthesia and were maintained in an anesthesia state by intubation. The entire CPB circuit consisted of a reservoir, a membrane oxygenator, a roller pump, a heat exchanger and a heat cooler, all of which were connected via silicon tubes. The volume of the priming solution, composed of 6% HES130/0.4 and 125 IU heparin, was less than 12 ml. In the CPB group, a 22G catheter was placed in the left femoral artery for monitoring arterial blood pressure, a 20G catheter was placed in a tail artery for arterial inflow and a homemade, multiorificed catheter was inserted into a right jugular vein for venous drainage. After 90 minutes, the CPB process was terminated when vital signs were stable. In the sham group, the same surgical process was conducted except for the venous drainage. Post-oxygenator blood gas and hemodynamic parameters were measured at each time point before CPB, during CPB and after CPB. All CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable. The establishment of CPB without blood priming in rats can be achieved successfully. The rat model could be used to study short-term or long-term organ injury mechanisms caused by CPB. Furthermore, on the basis of the precise control of temperature and the depth of anesthesia, the DHCA model in rats could be developed further to study pathophysiological changes of neurological and other organ functions in the future.

Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

The objective of this study was to determine the pharmacokinetics of cefuroxime in children undergoing cardiopulmonary bypass (CPB) for cardiovascular surgery. A prospective study. A tertiary pediatric teaching hospital. Infants and children undergoing CPB were enrolled in the study. An initial dose (mean, 24.2 ± 1.6 mg/kg) of cefuroxime was administered before surgical incision, and a second dose (mean, 14.4 ± 7.9 mg/kg) was administered in the CPB prime solution. Serial blood samples were obtained before, during, and after the CPB process. Samples were shipped on dry ice to the analytic laboratory and concentrations determined by a validated high-performance liquid chromatography method. A 2-compartment pharmacokinetic model was fitted to the data using maximum a priori-Bayesian estimation, with weight as a covariate. Monte Carlo simulations of a single-dose (25 mg/kg pre-CPB) approach and a 2-dose (25 mg/kg pre- and 12.5-mg/kg prime solution dose) approach were performed. Fifteen subjects (9 males/6 females) were enrolled in the study, with median (range) age and weight of 11 (3-34) months and 9.5 (4.5-15.4) kg, respectively. The median (range) duration of CPB was 136 (71-243) minutes. Median and range cefuroxime pharmacokinetic parameters were as follows: maximum concentration (Cmax) dose, 1: 328 (150-512) μg/mL; systemic clearance, 0.050 (0.041-0.058) L/h/kg; steady-state volume of distribution, 0.213 (0.081-0.423) L/kg; volume of distribution in the central compartment, 0.081 (0.046-0.162) L/kg; and elimination half-life, 3.76 (1.03-6.81) hours. The median 8-hour post-dose-simulated cefuroxime concentrations were 26.5 and 16.0 mg/L for the 2-dose and single-dose regimens, respectively. Manufacturers recommend that pediatric doses of cefuroxime (25-50 mg/kg) can be used in infants and children undergoing CPB to maintain adequate serum concentrations for surgical-site infection prophylaxis. A second intraoperative dose, administered through the CPB circuit, provides no additional prophylactic advantage.

Continous quality improvement of perfusion practice: the role of electronic data collection and statistical control charts

In-hospital data collection may be used to improve the selection, operative techniques, and process of care for cardiac surgical patients. The aim of this report is to demonstrate the influence of the automated generation of quality indicators (QI) for cardiopulmonary bypass (CPB) and the implementation of a continuous quality improvement (CQI) programme on the CPB process of care. Adult patients undergoing CPB were divided into three consecutive groups: Group 1 (n = 363); no QI data feedback, Group 2 (n = 253); automated QI data feedback alone, and Group 3 (n = 363) data feedback and implementation of CQI. There were no significant differences in demographic, procedural or clinical outcomes for each group. Significant improvement, as determined by adherence to practice protocols and reduction in practice variation, was observed for cardiac index < 1.6 L/min/m2 (min), mean arterial pressure < 40 mmHg (min), venous saturation < 60% (min), arterial blood temperature of > 37.5 degrees C (min), minimum pCO2 (mmHg), maximum pCO2 (mmHg), and minimum pO2 (mmHg). There was no change in the minimum haemoglobin (g/dl) on bypass. Automated generation of QI resulted in improved adherence to process of care guidelines, highlighting the potential of electronic data collection. This technique is optimised in a CQI programme, utilising statistical control charts for data interpretation.

A Systematic Approach to the Understanding and Redesigning of Cardiopulmonary Bypass

Cardiopulmonary bypass (CPB) is a highly complex process. We developed a system to capture and study detailed information during cardiac surgery that serves as a framework for understanding variation that occurs during CPB. The system allows the surgical team to link unwanted variation (ie, hypotension) and unwanted events (ie, the production of microemboli) to the processes of care. A more thorough understanding of embolic activity and hemodynamic aberrations, precursors to both stroke and subtle neurologic injury, that occur during CPB, will allow the surgical team to identify high leverage, modifiable aspects of care and abate these precursors to patient injury. Multimodality simultaneous monitoring and recording of physiologic parameters, emboli in the CPB circuit and in the middle cerebral arteries, and cerebral NIRS during surgery was carried out in patients undergoing open heart surgery with CPB. A system was designed that captures physiologic data from the patient monitors and the heart-lung machine at 20-second intervals and time synchronizes all measures with a video recording of the surgical procedure. Emboli counts count in the CPB circuit and right and left middle cerebral arteries were continuously recorded. Video recordings depicting various surgical and perfusion techniques with associated embolic activity were provided to the surgical team. Wide variation in embolic counts, cerebral blood flow velocity, and physiologic parameters were observed. Periods of embolic activity and cerebral desaturation could be related to surgical and CPB processes of care. We have identified increased emboli counts in the CPB circuit and in the middle cerebral arteries related to the method of venous drainage, manipulation of the aorta, and anastomotic techniques. se of this model provides the surgical team detailed information about these precursors to neurologic injury. This system provides a systematic approach to the understanding and redesigning of CPB.

A model for cardiopulmonary bypass redesign.

A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB. We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient's surgical case video. To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels. Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.

PLASMA AND URINARY CYTOKINE HOMEOSTASIS AND RENAL FUNCTION DURING CARDIAC SURGERY WITHOUT CARDIOPULMONARY BYPASS

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-β-D-glucosaminidase (NAG)/creatinine and α1-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and α1-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary α1-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and α1-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.