Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass.

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.     

Cardiac interleukin-6 release and myocardial recovery after aortic crossclamping. Crystalloid versus blood cardioplegia

BACKGROUND: Pro-inflammatory cytokines may play an important role in patient response to cardiopulmonary bypass (CPB). Since the myocardium is proposed to be a major source of cytokines, we studied the influence of the cardiolpegia type on interleukin-6 release and early myocardial recovery. METHODS: Experimental design: prospective, randomized study. Setting: university hospital, operative and intensive care. Patients: 20 consecutive patients (3 females) scheduled for elective coronary artery bypass grafting (CABG), mean age 62.8+/-5 years, history of myocardial infarction 11/20, left ventricular ejection fraction 62.9+/-15%. Interventions: patients were operated on using randomly either cold blood cardioplegia (B, n = 10) or cold crystalloid cardioplegia (C, n = 10). Measures: plasma levels of interleukin-6 (IL-6) were measured prior to CPB, after aortic declamping, after CPB, 1 hour, 6 hours and 12 hours postoperatively. RESULTS: Groups were comparable with respect to demographic data, left ventricular function, number of grafts, CPB and aortic crossclamp time. Group B patients demonstrated significant lower IL-6 levels after 1 hour (210+/-108 vs. 578+/-443 pg/ml), 6 hours (204+/-91 vs. 1210+/-671 pg/ml) and 12 hours (174+/-97 vs. 971+/-623 pg/ml). Post-CPB cardiac index was superior in group B (3.9+/-0.3 vs. 3.2+/-0.3 l/min/m2, p<0.05) with similar doses of inotropes. Group B patients could earlier be weaned off respirator (10+/-4 vs. 13+/-4 hours, p<0.05) and showed minor blood loss (635+/-211 vs. 918+/-347 ml, p<0.05). CONCLUSIONS: Inflammatory response to CPB is associated with delayed myocardial recovery. The use of blood cardioplegia may attenuate inflammatory reactions.     

The effect of combined preinduction thoracic epidural anaesthesia and glucocorticoid administration on perioperative interleukin-10 levels and hyperglycemia. A randomized controlled trial

AIM: Anti-inflammatory cytokines such as interleukin-10 (IL-10) play a key role in the anti-inflammatory cascade after cardiopulmonary bypass (CPB). Even moderate hyperglycemia can increase mortality/morbidity, stroke, and myocardial infarction after coronary artery bypass grafting (CABG). The purpose of our study was to investigate whether preinduction thoracic epidural anesthesia (TEA) and preinduction glucocorticoid have an effect on perioperative anti-inflammatory and perioperative hyperglycemia in patients undergoing CABG with CPB. METHODS: Sixty low-risk patients (n=60) undergoing elective CABG were randomly allocated into 4 groups: Group corticosteroid (Group S) (n=15) received 6-methylprednisolone 15 mg/kg IV 60 min before induction; Group TEA+corticosteroid (Group TEA+S) (n=15) received 20 mg bupivacaine in bolus 60 min before induction followed by 20 mg/h bupivacaine infusion intraoperatively and postoperatively via epidural catheter. Group TEA (n=15) received 20 mg bupivacaine in bolus 60 min before induction followed by 20 mg/h bupivacaine infusion intraoperatively and postoperatively via epidural catheter. Group control (Group C) (n=15) received neither preinduction TEA nor a preinduction steroid. Blood samples were sequentially taken before surgery (baseline), before CPB, 1 h after CPB, in the intensive care unit (ICU) and 24 h after surgery from an indwelling radial arterial catheter. RESULTS: Before CPB, circulating IL-10 levels were higher in groups TEA+S and S than in group C (P<0.05). At 1 h after CPB, IL-10 levels were higher in groups TEA+S and S than in group C (P<0.001). Before CPB and at 1 h after CPB, IL-10 levels were lower in group TEA than in group C (P<0.05). Before CPB, glucose levels were higher in group S than in groups TEA, C or TEA+S (P<0.001; P<0.05). There was no significant difference in glucose levels between groups TEA, TEA+S and C. At 1 hour after CPB, glucose levels were significantly lower in groups TEA and TEA+S than in groups S and C (P<0.001; P<0.05). At 1 hour after CPB, glucose levels were significantly higher in group S than in group C (P<0.05). At ICU, glucose levels were significantly lower in group TEA than in groups S, C and TEA+S (P<0.001; P<0.05). CONCLUSION: The study results show that preinduction TEA improves glucose homeostasis during the perioperative 24-h period in CABG surgery. In addition, we found that while preinduction TEA reduced blood IL-10 levels, preinduction glucocorticoid and TEA+S increased the circulating levels of IL-10.     

The release of systemic inflammatory mediators is independent of cardiopulmonary bypass temperature

OBJECTIVE: The aim of this study was to investigate the effect of systemic CPB temperature on the production of the key mediators of the systemic inflammatory response to coronary artery bypass graft (CABG) surgery. DESIGN: Randomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing first-time CABG surgery. INTERVENTIONS: The patients were randomized to hypothermic (32 degrees C, n = 15) or normothermic (36 degrees C, n = 15) CPB. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), cortisol, and neutrophils were measured the day before operation, at closure of the sternum, and 4, 16, and 44 hours later. The cytokine, CRP, cortisol, and neutrophil responses were independent of temperature during CPB with peak concentrations of IL-10 at closure of the sternum followed by IL-6, IL-8, cortisol, neutrophils, and finally CRP. A correlation between maximal plasma concentrations of IL-10 and cortisol was seen in both groups after surgery (p = 0.02). Drainage after surgery was lower after normothermic CPB (p=0.02), with no difference in the requirement for blood transfusion. All patients were discharged from the intensive care unit within 24 hours after surgery. CONCLUSIONS: The release of systemic inflammatory mediators after cardiac surgery was independent of mild hypothermia (32 degrees C) versus normothermia (36 degrees C) during CPB.     

Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study

OBJECTIVE--Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN--Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS--C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION--OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.     

冠状动脉搭桥术后血浆可溶性Fas及其配体的变化

目的比较在心肺转流（CPB）或非CPB下冠状动脉搭桥术（cABG）后可溶性Fas（sFas）和可溶性Fas配体（sFasL）的血浆浓度变化。方法19例病人分别在CPB（CPB组，n=9）或非CPB（非CPB组，n=10）下行择期cABG。术前、术毕和术后取血测定白细胞介素-6（IL-6）、中性粒细胞弹性蛋白酶、sFas、sFasL血浆浓度。结果术毕、术后4h的IL-6和术毕、术后4、12h的中性粒细胞弹性蛋白酶非CPB组明显低于CPB组（P〈0．05或P〈0．01）。CPB组的sFas在术后4、12h明显升高（P〈0．05或P〈0．01），非CPB组在术后12h明显升高（P〈0．01），术后24h恢复至术前水平。两组的sFasL在术毕和术后4、12h均明显升高（P〈0．05或P〈0．01），术后24h恢复至术前水平；其中术后12h非CPB组明显低于CPB组（P〈0．05）。结论CPB或非CPB下行cABG均导致sFas和sFasL血浆浓度升高，但CPB的应用使sFasL血浆浓度升高得更多。sFasL血浆浓度可反映机体炎性反应的程度。     

The heart produces but the lungs consume proinflammatory cytokines following cardiopulmonary bypass.

OBJECTIVE: Proinflammatory cytokines, such as interleukin-6 (IL-6), and soluble adhesion molecules, such as E-selectin, may play an important role in patient response to cardiopulmonary bypass (CPB). We sought to define whether the heart and the lungs serve as important sources of these inflammatory mediators under clinical conditions of myocardial revascularization using CPB and cardioplegic arrest. METHODS: Plasma levels of IL-6 and E-selectin were measured in coronary sinus (CS), arterial, pulmonary arterial (PA) and left atrial (LA) blood samples taken from 12 consecutive patients (68.3 +/- 11 years; five females) undergoing coronary artery bypass grafting (CABG). Blood samples were collected preoperatively, after reperfusion, and 1, 6, 12 and 18 h following surgery. CS and LA blood was drawn using transcutaneous catheters. PA artery blood was obtained through a Swan-Ganz catheter. Cytokine levels were determined by standard enzyme linked immunosorbent assay (ELISA) technique. RESULTS: A mean of 3.8 +/- 1 coronary anastomoses were performed. The CPB time and aortic X-clamp time were 91 +/- 15 and 45 +/- 10 min, respectively. IL-6 levels increased significantly after CPB and peaked 6 h postoperatively. There was also a significant increase of E-selectin levels with an onset at 1 h and a peak at 12 h postoperatively. At all time points the IL-6 and E-selectin concentrations were significantly higher in the CS than in arterial blood. In contrast, the levels of both mediators measured in the LA were significantly lower than those in the PA. CONCLUSION: The reperfusion of ischemic myocardium during CABG results in a significant increase in plasma levels of IL-6 and E-selectin. Our data indicate that the myocardium, but not the lungs, is a predominant source of IL-6 and E-selectin release following CPB. The lungs may consume rather than release those mediators during reperfusion. Not the CPB per se, but the myocardial ischemia seems to be crucial in the pathogenesis of the inflammatory response observed following open heart surgery.     

Nonthyroidal illness syndrome in off-pump coronary artery bypass grafting

BACKGROUND: Cardiopulmonary bypass (CPB) is an established cause of nonthyroidal illness syndrome (NTIS). Off-pump coronary artery bypass (OPCAB) has been reported to be less invasive than coronary artery bypass grafting (CABG) with CPB. We prospectively evaluated thyroid metabolism in OPCAB patients. METHODS: We analyzed free thyroid hormones (FT3 and FT4), thyroid-stimulating hormone (TSH), and reverse T3 (rT3) in 20 consecutive patients undergoing CABG surgery. Nine patients underwent CABG with CPB, and 11 underwent OPCAB. Blood samples were taken on admission, on the day of surgery (7:30 AM), after sternotomy, at the end of the operation, and at 2, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours postoperatively. The concentrations of FT3, FT4, and TSH were determined on each sample. Reverse T3 concentration was measured in 10 patients up to 48 hours and at 144 hours postoperatively. RESULTS: Baseline, operative, and postoperative variables were similar in the two groups. FT3 concentration dropped significantly (p < 0.0001), reaching its lowest value 12 hours postoperatively. There were no significant differences between CPB and OPCAB patients. FT4 varied significantly in both groups (p < 0.0001), but remained in the normal range. TSH variation was not significant. rT3 concentration rose significantly (p = 0.0002) in both groups, peaking 24 hours after surgery. CONCLUSIONS. OPCAB induces a NTIS similar to that observed after CPB, probably due to the inhibition of T4 conversion to T3. This finding suggests that NTIS is a nonspecific response to stress. CPB should not be considered as the sole trigger of NTIS in cardiac surgical patients.     

Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) results in expression of cytokines and adhesion molecules (AM) with subsequent inflammatory response. The purpose of the study was to evaluate the clinical impact of modified ultrafiltration (MUF) and its efficacy in reducing cytokines and AM following coronary artery bypass grafting (CABG) in adults. METHODS: A prospective randomized study of 97 patients undergoing elective CABG was designed. Fifty patients were operated on using normothermic and 47 patients using hypothermic CPB. The normothermic group was subdivided into a group with modified ultrafiltration (n = 30) and a group without MUF (n = 20). In the hypothermic group 30 patients received MUF compared to 17 patients serving as controls. MUF was instituted after CPB for 15 min through the arterial and venous bypass circuit lines. Cytokines (IL-6, IL-8, TNF-alpha, IL-2R) and adhesion molecules (sE-selectin, sICAM-1) were measured preoperatively, pre-MUF, in the ultrafiltrate, 24 h, 48 h and 6 days after surgery by chemiluminescent enzyme immunometric assay or enzyme-linked immunosorbent assay (ELISA). Clinical parameters were collected prospectively until discharge. RESULTS: In all patients AM and cytokines were significantly elevated after normothermic and hypothemic CPB. AM and cytokines were significantly higher in hypothermia compared to normothermia. In hypothermic CPB sE-selectin was decreased after 24 h by 37% (P < 0.0063) and by 40% (P < 0.0027) after 48 h postoperatively. ICAM-1 was reduced by 43% (P < 0.0001) after 24 h and by 60% (P < 0.0001) after 6 days. Similar results were seen in cytokines with reduction up to 60% after 24 h. Changes after 48 h were noticeable but not significant. Reduction of AM and cytokines after normothermic CPB was minimal. Neither in normothermia, nor in hypothermia has sIL-2R been effectively removed from the circulation. There were no significant differences in the clinical variables between the patients with or without MUF. CONCLUSION: AM and cytokines are significantly elevated after hypothermic CPB compared to normothermic CPB. MUF led to a significant reduction in cytokine and AM levels after hypothermic CPB, except for IL-2R. MUF showed minimal effect in normothermia. We conclude that MUF is an efficient way to remove cytokines and AM. However, we were unable to demonstrate any significant impact of MUF in outcome of adults after elective CABG.     

Off-pump coronary artery bypass grafting attenuates proinflammatory markers

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) has been considered the main causative factors of postoperative inflammatory reactions. The aim of this study was to compare surrogate markers of the proinflammatory response in patients who underwent coronary artery bypass grafting (CABG) with or without CPB. Methods and Results: Twenty patients undergoing first-time CABG were enrolled in the study, 10 with and 10 without CPB. Blood samples were drawn at the following times: at the anesthetic induction, the end of surgery, and thereafter at 12 and 24 hours postoperatively. Neutrophil elastase, interleukin (IL)-6 , and serum soluble Fas were chosen to evaluate the extent of the systemic inflammatory response. The groups were similar in terms of age, gender ratio, number of grafts per patient. There were no operative mortality or serious postoperative complications. Two of each group received blood transfusion postoperatively. Neutrophil elastase showed a significantly higher value in the on-pump group compared with the off-pump group at the end of surgery. Soluble Fas level showed a higher value at the end of surgery compared with baseline, while it had no significant changes in the off-pump patients. IL-6 levels in the on-pump group were consistently higher compared to the off-pump group but showed no statistically significant differences between the groups. Conclusion: Compared with off-pump CABG, on pump CABG induced higher serum levels of proinflammatory markers including neutrophil elastase and soluble Fas.     

Expression of adhesion molecules and cytokines after coronary artery bypass grafting during normothermic and hypothermic cardiac arrest

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) results in vascular injury and tissue damage which involves leukocyte-endothelial interactions mediated by cytokines and adhesion molecules. This study was designed to demonstrate the effect of normothermic and hypothermic CPB to cytokine and soluble adhesion molecule levels in adults and to determine whether these levels correlate to the patients postoperative course. Design and patients: In 25 patients after normothermic and in 25 patients after hypothermic coronary artery bypass grafting with cardiopulmonary bypass (CPB), blood samples for cytokine and soluble adhesion molecule analysis were taken preoperatively, 24, 36, 48 h, and 6 days postoperatively. Soluble adhesion molecules (sE-selectin, sICAM-1) were measured by ELISA and cytokines (TNF-, IL-6, IL-8) by chemilumenscent-immunoassay. Clinical data were collected prospectively. Results: Postoperatively, adhesion molecule and cytokine levels were significantly elevated after CPB. Mean plasma levels of sICAM-1 was 2.4-fold higher after 6 days. Mean plasma concentration of sE-selectin peaked after 48 h with a 2-fold increase compared to normothermic conditions. In the hypothermia group sICAM-1, sE-selectin, IL-6, and IL-8 showed significantly higher levels (P<0.0057, P<0.0012, P<0.0419, P<0.0145) after 24 h compared to the normothermia group. No clinical differences were seen. Conclusion: Adhesion molecules and cytokines are elevated after CPB. Patients after hypothermic CPB show significant higher sICAM-1, sE-selectin, IL-6, and IL-8 levels after 24 h compared to normothermic conditions. These results are mainly due to longer CPB and crossclamp times but do not alter the patient's postoperative course.     

Inflammatory response after coronary revascularization: off-pump versus on-pump (heparin-coated circuits and poly2methoxyethylacrylate-coated circuits).

OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) may reduce the inflammatory response associated with cardiopulmonary bypass (CPB) and contribute to minimizing postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits were developed to reduce such complications. We compared the postoperative inflammatory response with or without CPB. METHODS: Eighteen consecutive patients undergoing isolated coronary artery bypass grafting (CABG) were divided into three groups: OPCAB group (n=6), heparin-coated circuits group (n=6), PMEA-coated circuits group (n=6). The plasma concentrations of the following inflammatory markers were measured: cytokines [interleukin (IL-10)], polymorphonuclear elastase (PMNE), coagulofibrinolytic factor [thrombin-antithrombin III complex (TAT)], complement factor (C3a). RESULTS: At the end of CPB, IL-10 and TAT concentrations were significantly different among the three groups (OPCAB group < PMEA-coated group < heparin-coated group). The PMNE concentration was significantly lower in the OPCAB group and the heparin-coated group as compared to the PMEA-coated group both at the end of CPB and 4 hours after CPB. C3a concentration was significantly lower in the OPCAB group than in the CPB groups at the end of CPB. Clinical variables did not differ significantly among the three groups. CONCLUSION: Off-pump CABG is associated with a reduction in the inflammatory response when compared with on-pump CABG, using either PMEA-coated or heparin-coated circuits.     

常规与非体外循环冠状动脉旁路移植术炎症因子比较

目的：比较多支冠状动脉（冠脉）病变行常规体外循环冠状动脉旁路移植术（CABG）和非体外循环冠状动脉旁路移植术（OPCAB）围术期心肌损伤和炎症因子的变化情况。方法：CABG组（A组，13例），OPCAB组（B组，22例）。分别于麻醉诱导后、手术结束后即刻、术后24h和48h进行血样检测，分别测定TNF－α、IL-1β、IL-8和IL－10水平。另外记录围手术期各项临床指标如引流量、输血量、呼吸机使用时间和发热时间等。结果：两组在年龄、冠脉病变程度、心功能和血管旁路移植数目上相似。术后IL－8水平OPCAB组相对稍高，但两组无显著差异。围术期CABG组IL－1、TNF较OPCAB明显为高（P＜0．05）。但炎症因子IL－10 OPCAB组却较CABG组明显升高（P＜0．05），术后24h达高峰。最后，CABG较OPCAB病人呼吸机使用时间延长且发热时间延长。结论：与CABG组相比，OPCAB组围术期炎症反应和术后并发发症明显降低。     

Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10

BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 play a key role in the inflammatory cascade after cardiopulmonary bypass (CPB) and may induce cardiac and lung dysfunction. Antiinflammatory cytokines such as IL-10 may also significantly limit these complications. Corticosteroid administration before CPB increases blood IL-10 levels and prevents proinflammatory cytokine release. This study examined the association of increased release of IL-10, stimulated by steroid pretreatment, with reduced myocardial and lung injury after CPB. METHODS: Twenty patients undergoing coronary artery bypass grafting (CABG) received either preoperative steroid (n = 10, protocol group) or no steroid (n = 10, control group). Perioperative care was standardized, and all caregivers were blinded to treatment group. Seven intervals of blood samples were obtained and assayed for TNF-alpha, IL-6, IL-8, and IL-10. Various hemodynamic and pulmonary measurements were obtained perioperatively. Levels of MB isoenzyme creatine kinase (CK-MB) were also measured. RESULTS: In the protocol group, proinflammatory cytokines were significantly reduced while IL-10 levels were much higher after CPB. The protocol group had a lower alveolar-arterial oxygen gradient and higher ratio of arterial oxygen pressure to fraction of inspired oxygen after CPB. Creatine kinase (CK) and CK-MB were reduced in the patients treated with steroid. Correlations were found between plasma cytokines levels and cardiac index, and CK-MB. CONCLUSIONS: This study confirms that corticosteroids abolish proinflammatory cytokines release and increase blood IL-10 levels after CPB. Our findings demonstrate a greater release of IL-10 induced by steroid pretreatment, and better heart and lung protection after CPB.     

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.     

Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery

BACKGROUND: Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery. METHODS: Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios. RESULTS: Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05). CONCLUSIONS: Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.     

Autotransfusion after cardiac surgery. Hematological, biochemical and immunological properties of shed mediastinal blood

OBJECTIVE: Although it is well documented that the reinfusion of unwashed shed blood reduces postoperative homologous blood requirements after cardiac surgery, the efficacy and safety of the technique has been questioned on the basis of several possible adverse effects. We therefore aimed to evaluate the extent of mediastinal shed blood damage by cardiopulmonary bypass (CPB) and extravasation.Patients and METHOD: Five perioperative blood samples were obtained from each of the 20 patients undergoing cardiac surgery: by venipuncture, during the induction of anesthesia (sample 1), at the end of CPB (sample 2), and one hour after mediastinal shed blood reinfusion (sample 5), and from the cardiotomy reservoir at the first and sixth postoperative hours (samples 3 and 4). Hematological, biochemical and immunological parameters, and the metabolic and functional status of shed erythrocytes were studied in each sample. RESULTS: Hematological and biochemical values were lower at the end of CPB and in shed blood, but not after reinfusion. Inversely, plasma free hemoglobin levels and echinocyte formation were elevated after CPB and in shed blood, the latter correlating with the decrease in serum albumin levels due to hemodilution. No alterations were detected in erythrocyte median corpuscular fragility, D-glucose, L-phenylalanine and L-serine uptakes or 2,3-bisphosphoglycerate content. Plasma IL-10 levels were elevated at the end of CPB, whereas shed blood showed increased levels of IL-1beta, IL-6 and IL-10. Shed blood retrieval did not modify the pattern of circulating cytokines found at the end of CPB. CONCLUSIONS: Shed mediastinal blood salvaged after cardiac surgery seems to be an excellent source of red cells, which conserve functional and metabolic status; once reinfused, shed blood does not modify the inflammatory response of the patient to CPB.     

Off-pump versus on-pump coronary artery bypass surgery and postoperative pulmonary dysfunction

OBJECTIVE: To investigate how off-pump coronary artery bypass grafting (CABG) affects postoperative pulmonary function when compared with on-pump CABG. DESIGN: Prospective clinical study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Adult patients (n = 39) undergoing elective coronary artery bypass surgery with or without cardiopulmonary bypass. INTERVENTIONS: Two groups of patients were compared: 19 consecutive patients undergoing off-pump CABG surgery and 20 consecutive patients undergoing conventional CABG surgery. MEASUREMENTS AND MAIN RESULTS: Pulmonary function tests (flow volume loops and lung volumes with plethysmography) were done preoperatively and 72 hours postoperatively. Arterial blood gases and PaO2/FIO2 were measured at various stages. Sequential chest x-rays were obtained and evaluated for pleural changes, pulmonary edema, and atelectasis. In both groups, PaO2/FIO2 ratios decreased progressively throughout the perioperative period, with no significant differences between the groups at any stage during the study. There was a significant decline in postoperative pulmonary function tests in both groups, but there was no difference between groups at 72 hours postoperatively. No differences were found in the time to extubation, atelectasis scores, or postoperative complications. CONCLUSIONS: Off-pump CABG does not confer major protection from postoperative pulmonary dysfunction compared with CABG surgery with CPB. Strategies for minimizing pulmonary impairment after CABG surgery should be directed to factors other than the use of CPB.     

Soluble Adhesion Molecules and Myocardial Injury during Coronary Artery Bypass Grafting

Abstract Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase–muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.     

Cerebral inflammatory response during and after cardiac surgery

BACKGROUND AND OBJECTIVE: Neurological dysfunction is a common problem after cardiac surgery with cardiopulmonary bypass (CPB). Cerebral ischaemia associated with the use of CPB may result in a release of neuronal-ischaemic markers and a subsequent cerebral inflammatory response which may additionally release inflammatory cytokines. In order to locate the origin and to quantify the release of neuronal-ischaemic markers and cytokines we investigated arterial-cerebral venous concentration gradients during and after CPB in a clinical setting. METHODS: In twenty-five patients scheduled for coronary artery bypass grafting surgery we measured the plasma concentration of neuron-specific enolase, S-100beta protein as well as interleukins (IL) IL-6, IL-8 and IL-10 from arterial and cerebral venous blood samples prior to surgery (baseline), during hypothermic CPB at 32 degrees C, after termination of bypass, as well as 2, 4 and 6 h after admission to the intensive care unit. RESULTS: Arterial-cerebral venous concentration gradients of neuron-specific enolase, S-100beta, IL-6, IL-8 and IL-10 were neither detectable during nor after CPB. Compared to the baseline period, S-100beta and neuron-specific enolase significantly increased during hypothermic CPB. After termination of CPB, neuronal-ischaemic markers as well as cytokines were increased and remained elevated during the investigated time course without reaching baseline values. CONCLUSIONS: Although we found an overall increase in plasma concentrations of neuronal-ischaemic markers, IL-6, IL-8 and IL-10 during and after CPB, arterial-cerebral venous gradients were not detectable for any of these parameters. Our results suggest that the increase of investigated parameters associated with the use of CPB are not primarily caused by a cerebral inflammatory response but rather reflect a release from other sources in the systemic circulation.