HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Online Discussion Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giomarelli, P. Articles by Biagioli, B. Search for Related Content PubMed PubMed Citation Articles by Giomarelli, P. Articles by Biagioli, B. Related Collections Extracorporeal circulation

Ann Thorac Surg 2003;76:117-123
© 2003 The Society of Thoracic Surgeons

---

Original article: cardiovascular

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

^a Institute of Thoracic and Cardiovascular Surgery, University of Siena, Siena, Italy

Accepted for publication January 24, 2003.

^* Address reprint requests to Dr Giomarelli, Istituto di Chirurgia Toracica e Cardiovascolare, Università di Siena, Viale Bracci, 1, 53100 Siena, Italy.
e-mail: giomarelli{at}unisi.it

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor- (TNF-), 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-, 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.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 

This article has been selected for the open discussion forum on the CTSNet website: http://www.ctsnet.org/discuss

 

The term "postperfusion syndrome" has been used to indicate various dysfunction of the kidneys, lungs, heart, and clotting system frequently found in patients undergoing extracorporeal circulation [1]. This syndrome is characterized by activation of the clotting system, the kallikrein system, the complement system, and neutrophils and monocytes. These blood proteins and cells, together with other blood elements, produce the vasoactive and cytotoxic substances and microemboli that cause myocardial and respiratory injury, increasing morbidity and mortality [2].

The reliable measurements of endogenous mediators, such as tumor necrosis factor- (TNF-), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) has allowed to clarify the pathway of this inflammatory response, becoming an important instrument in clinical setting [3]. The presence of these mediators is closely linked to a ubiquitous nuclear transcription factor (nuclear factor kappa B, NFB), involved in the generation of a number of various gene products [4].

Tumor necrosis factor-, a proinflammatory cytokine, is produced by macrophages and monocytes. It is a potent pyrogen and activator of neutrophil and endothelial cells, acting through two distinct TNF receptors (TNFR1, TNFR2) [5].

Interleukin-6 has proinflammatory and antiinflammatory properties. It stimulates the release of hepatic proteins and is involved in neutrophil-mediated ischemia/reperfusion injury. It induces glucocorticoid release and suppresses the action of IL-1 and TNF- [6].

Interleukin-8, a proinflammatory cytokine released by cells, such as endothelial cells, monocytes, and T cells, has been recognized as a relevant mediator of organ dysfunction based on its major role of recruitment and activation of leukocytes, seen in adult respiratory distress syndrome [7]. The levels of IL-8 correlate positively with the levels of cardiac Troponin I, suggesting a role for IL-8 in myocardial injury after cardiac surgery [8].

Interleukin-10 is a potent antiinflammatory cytokine that reduces neutrophil adhesion to activated endothelial cells [9]. Experimentally IL-10 has been found to protect against ischemic damage, but there is no clear evidence of its relationship to heart function in humans [10]. Interleukin-10 is significant in the amelioration of ischemia/reperfusion injury as demonstrated in IL-10-deficient mice [11].

Steroidal pretreatment has been used in operations involving cardiopulmonary bypass (CPB) for more than 30 years, but their role in improving clinical outcome after CPB is still not clear [12]. The main mechanism proposed is the inhibition of NFB through direct protein–protein interaction, hence reduced levels of proinflammatory cytokines and increased of antiinflammatory mediators, particularly IL-10 [4].

We carried out a prospective, randomized, double-blind, placebo-controlled clinical study of a homogeneous group of patients undergoing coronary artery bypass grafting (CABG). The aim was to evaluate whether a systemic response characterized by lower values of IL-8 and IL-6, and greater levels of IL-10 stimulated by steroid treatment, is associated with improved heart and lung protection after heart surgery.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Patients
After approval by the Local Ethics Committee, we studied 20 patients undergoing CABG between January 2002 and April 2002 (total number of CABG cases performed during the same period was 119). Exclusion criteria were urgency/emergency surgery; previous heart surgery; valve or combined CABG and valve surgery; left ventricular ejection less than 0.35; diabetics on insulin therapy; active gastropathic disorder; chronic obstructive pulmonary disease on therapy; preoperative use of steroids and contraindications to steroid administration; Cleveland Clinic score of 4 or higher [13].

Patients were randomized according to a computer-generated sequence and assigned either to the standard care control group (n = 10), or to the protocol group (n = 10) in which steroid treatment was added. According to similar studies [14], the protocol group received 1 g intravenous methylprednisolone (MPS) preoperatively and 125 mg at the end of CPB. In the intensive care unit (ICU), four additional 125-mg doses were given every 6 hours. Patients in the control group received similar volumes of isotonic sodium chloride solution at the same times. An anesthesia nurse performed the randomization and prepared the syringes of blinded solution that were administered by the anesthesiologist managing the case. All physicians and nursing staff caring for the patient perioperatively were unaware of the treatment groups.

Anesthesia, cardiopulmonary bypass, and myocardial protection
The anesthetic technique was standardized and consisted of 5 µg/kg fentanyl, 0.3 mg/kg diazepam, and 0.1 mg/kg pancuronium to perform intubation; less than 1% isoflurane and 0.01 mg · kg^-1 · min^-1 atracurium were used for maintenance; 7 to 10 µg/kg fentanyl was administered before sternotomy. At the beginning of CPB, isoflurane was suspended and replaced with 5 mg/kg thiopentone; 4 to 6 mg · kg^-1 · h^-1 propofol was also started.

Extracorporeal circulation was instituted with a roller pump and a hollow-fiber oxygenator (Capiox SX 18; Terumo Corporation, Tokyo, Japan) primed with 1,500 mL (±200 mL) buffered crystalloid solution. During CPB, hematocrit was maintained between 22% and 25%. Myocardial protection was obtained according to the protocol of University of California at Los Angeles Medical Center [15]. A pump flow rate of 2.2 to 2.4 L · min^-1 · m^-2 was used. Before cross-clamp release, warm modified cardioplegic reperfusion was performed [15]. Moderate systemic hypothermia (30° to 32°C) and topical hypothermia were used. The patients were weaned off CPB when rectal temperature had reached 34°C. In the ICU, patients were weaned off mechanical ventilation as soon as they were awake and breathing faster than the ventilator set rate and when the following criteria were met: patient obeying commands; stable and adequate hemodynamics; no significant arrhythmia; core temperature of higher than 36°C; chest tube drainage of less than 100 mL/h for 2 consecutive hours; diuresis of more than 1 mL/kg per hour; pH of higher than 7.35; arterial carbon dioxide pressure (PaCO₂) of less than 50 mm Hg; arterial oxygen pressure (PaO₂) of more than 70 mm Hg; and oxygen saturation as measured by pulse oximetry of 92% or higher with the patient breathing less than 50% oxygen.

Cytokine measurement
Blood was withdrawn from the radial catheter and collected in different phlebotomy tubes containing ethylene diamine tetraacetic acid. Platelet-poor plasma was prepared by centrifuging at 3,000g for 10 minutes. The plasma was stored in polypropylene tubes at -80°C until use. Interleukin-6, IL-8, IL-10 and TNF- were measured in all samples with enzyme-linked immunosorbent assay kits at the following intervals: T1 = 15 minutes after intubation, T2 = 5 minutes after aortic cross-clamp release, T3 = 10 minutes after CPB, T4 = 3 hours after CPB, T5 = 12 hours after CPB, T6 = 24 hours after CPB, and T7 = 4 days after operation.

Hemodynamic, ventilatory, and enzyme measurements
Mean arterial pressure, cardiac index (CI, by thermodilution), systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure were recorded at the same intervals, except T7. Also, alveolar-arterial oxygen gradient (A-aDO₂), respiratory index (RI), shunt (Qs/Qt), dead space (Vd/Vt), arterial-venous difference in oxygen (a-vO₂D), oxygen extraction ratio (O₂ER), and oxygen delivery (DO₂) were calculated using standard formulas. Serial temperature measurements were also obtained.

Blood specimens were obtained for the analysis of cardiac enzymes: total serum activity of creatine kinase (CK) was determined by enzymatic method and the activity of MB isoenzyme creatine kinase (CK-MB) was quantified by the immunoassay method (Boehringer, Mannheim, Germany). CK and CK-MB were evaluated at following intervals: T0 = basal value, T4 = 3 hours after CPB, T5 = 12 hours after CPB, T6 = 24 hours after CPB and T7 = 4 days after operation.

Statistical analysis
Statistical analysis was performed with SPSS software (SPSS Inc, Chicago, IL). Fisher exact test was used for categorical data. Student’s t test (or Mann-Whitney U-test, where appropriate) was used to test the difference between means in two groups regarding demographic and clinical characteristics of patients and appropriate perioperative data. To account for repeated measurements of perioperative hemodynamic and pulmonary data, and cytokines and cardiac enzymes values, repeated-measures analysis of variance (ANOVA) was used. Correlation between cytokine levels and hemodynamics was established by linear regression models. Statistical significance was taken for p less than 0.05.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Patients were similar with regard to preoperative and intraoperative data (Table 1). Repeated-measures ANOVA revealed that differences were significant over times within groups for A-aDO₂ (p < 0.05), respiratory index (p < 0.05), and ratio of arterial oxygen pressure (PaO₂) to fraction of inspired oxygen (FiO₂) (p < 0.05); nevertheless, differences were significant between groups only at T5 and T6 (Table 2). The other ventilatory measurements were similar in both groups.

Plasma cytokine levels were significantly different over times within groups (p < 0.01) and between groups: TNF-, IL-6, and IL-8 were higher in the control group and peaked from T3 to T7 (Table 3). The IL-10 level was higher in the protocol group from T2 to T6, reaching a peak value at T3 (Fig 1).

View larger version (12K): [in this window] [in a new window]   Fig 1. Plasma interleukin (IL)-10 levels. Data are mean ± SD. T1 = 15 minutes after intubation; T2 = 5 minutes after aortic cross-clamp release; T3 = 10 minutes after cardiopulmonary bypass (CPB); T4 = 3 hours after CPB; T5 = 12 hours after CPB; T6 = 24 hours after CPB; T7 = 4 days after operation. = control; • = protocol. **p < 0.01 and ***p < 0.001; ANOVA.

View larger version (19K): [in this window] [in a new window]   Fig 2. Plots showing relationships between cardiac index (CI) and interleukin (IL)-10 and IL-6. (A) CI and IL-10 concentration 10 minutes after cardiopulmonary bypass (T3 time) (r = 0.74; p < 0.001). (B) CI and IL-6 levels at the same time (r = -0.61; p < 0.01).

View larger version (18K): [in this window] [in a new window]   Fig 3. (A) Plasma levels of creatine kinase (CK) and (B) MB isoenzyme creatine kinase (CK-MB). At T4 and T5 a significant difference is found between groups (*p < 0.05; ANOVA). T0 = basal value; T4 = 3 hours after cardiopulmonary bypass (CPB); T5 = 12 hours after CPB; T6 = 24 hours after CPB; T7 = 4 days after operation. = control; = protocol.

View larger version (15K): [in this window] [in a new window]   Fig 4. Plots showing relationships between plasma levels of creatine kinase and MB isoenzyme creatine kinase (CK-MB) and cytokines 3 hours after cardiopulmonary bypass (T4 time). (A) CK-MB and interleukin (IL)-10 (r = -0.54; p < 0.05). (B) CK-MB and IL-8 (r = 0.49; p < 0.05). (C) CK-MB and IL-6 (r = 0.59; p < 0.01).

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Cytokine concentrations showed different patterns in the two groups of patients, indicating a reduced inflammatory response associated with a higher level of IL-10 in patients treated with steroids. This result correlates with other studies of MPS-treated patients and with similar patterns at the different observation times of other cytokine studies [8, 16, 17].

The groups were well matched with regard to the peri- and postoperative stability data, to the intubation time, and to similar hemodynamic variables. In similar studies, Tassani [14] reported a shorter intubation time in MPS patients than in controls and Chaney and coworkers [18] found a longer intubation time in MPS patients. Tassani’s hypothesis on the influence of nursing and administration of sedative drugs and analgesics is certainly possible [14]. However, another reason may explain the contradictory results: the dose used in the study by Tassani [14], as in our study, was much lower than that administered by Chaney and colleagues [18] of two doses of 30 mg/kg (4.8 g for 80 kg body weight). Side effects from the corticosteroids could be pronounced and have a negative influence on pulmonary oxygenation [12]. In fact, Chaney [12] demonstrated a prolonged intubation time in patients who received a much higher dose of methylprednisolone (2 x 30 mg/kg versus 2 x 15 mg/kg). In our study the extubation time was similar, but significant differences were found between groups with regard to A-aDO₂, PaO₂ to FiO₂ ratio, and respiratory index (12 hours after CPB, but still under mechanical ventilation, and after 12 hours of spontaneous breathing). This finding could reflect different degrees of lung damage (Table 2), confirming a better lung protection and a decrease in inflammatory reaction (particularly IL-6 and IL-8) in the protocol group (Table 3). As the clinical courses of the two groups did not show modifications, differing "inflammatory status" may be the only cause of reduced lung function in the control group 12 and 24 hours after CPB (Table 2) [19, 20].

The CI was similar in both groups, yet higher at T3 and T4 in MPS-treated patients (Table 2). In a prospective, randomized, double-blind study, similar CI values were found by Chaney [12]. These results, although inconsistent with those from other studies [16], could be explained by different hypothermic or normothermic management of CPB, by differences in timing of steroid application, and by dosage and choice of corticosteroid [14].

At the T3 time we found a direct relationship between CI and IL-10, and an inverse relationship between CI and IL-6 (Fig 2). These results are consistent with other studies and could indicate the importance of the balance of proinflammatory and antiinflammatory cytokines for improving hemodynamic variables [21, 22]. These outcomes confirm the hypothesis of the potential antiinflammatory effects of IL-10 and its role on modulating cardiovascular effects; increased IL-10 values might suggest a better hemodynamic performance and a lower systemic inflammatory reaction [22].

Finally we found that CK and CK-MB levels were significantly reduced at T4 and T5 times in the protocol group (Fig 3). At T4, IL-10, IL-6, and IL-8 plasma levels correlated with CK and CK-MB levels (Fig 4). These results are consistent with the study of Wei and associates [23] and confirm the possibility that IL-6 and IL-8 levels may correlate with the severity of tissue damage induced by surgery and the inflammatory response to CPB [8]. Contrarily, IL-10 may protect the myocardium against ischemia-reperfusion injury after aortic clamping-declamping and may represent the endogenous response to limit the inflammatory response to CPB [21–24].

Yang and colleagues [11] evaluated the role of endogenous production of IL-10 in an experimental model of ischemia-reperfusion in mice. After 30 minutes of occlusion of the left anterior descending coronary artery and 6 hours of reperfusion, the infarcted myocardium was much thicker than that in IL-10-deficient mice. This result was confirmed by the significant increase in plasma levels of CK and CK-MB enzymes among injured mice [11].

The results of our present study agree with those of other studies of corticosteroid-treated or untreated patients, and with similar patterns at different observation times of other cytokine investigations. Preventive administration of corticosteroids, by reducing proinflammatory cytokine release and increasing blood IL-10 levels, may provide a better degree of lung and myocardial protection in patients undergoing CABG with extracorporeal circulation. However, because the inflammatory response is multifactorial [2, 25], combined therapies may be more efficient than a single intervention to improve outcome, and both pharmacological interventions and modifications of extracorporeal techniques might improve clinical results [25].

The small size of our study is not sufficient to assess clinical outcome. The main purpose was to investigate the effect of steroid on the cytokine balance and its possible influence on myocardial and lung injury after CPB. With the incidence of distinct end point such as clear adult respiratory distress syndrome or death being so low with current CPB techniques, well-planned randomized clinical trials have to be very large to show efficacy using new pharmacological interventions. If we are to make progress in eliminating post-CPB injuries, we may have to accept less distinct end points to determine efficacy, such as inflammatory mediator levels coupled with postoperative clinical variables such as A-aDO₂, PaO₂ to FiO₂ ratio, hemodynamics, and myocardial injury markers.

We conclude that MPS before cardiac surgery shifts the circulating cytokine profile toward the antiinflammatory course by inhibiting the systemic inflammatory response, and may improve lung and myocardial function after CPB. By reducing inflammatory and cytokine response to standard CPB procedures, cardiac surgery with preoperative administration of MPS may reasonably achieve greater success especially in the treatment of high-risk patient population.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Kirklin J.K. The postperfusion syndrome: inflammation and the damaging effects of cardiopulmonary bypass. In: Tinker J.H., ed. Cardiopulmonary bypass: current concept and controversies. Philadelphia: WB Saunders, 1989:131-146.
2. Edmunds L.H. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1998;66(Suppl):S12-S16.[Abstract/Free Full Text]
3. Wan S., LeClerc J.C., Vincent J.L. Cytokine responses to cardiopulmonary bypass. Lessons learned from cardiac transplantation. Ann Thorac Surg 1997;63:269-276.[Abstract/Free Full Text]
4. Lee J.I.K., Burckart G.J. Nuclear factor kappa B: important transcription factor and therapeutic target. J Clin Pharmacol 1998;38:981-993.[Abstract/Free Full Text]
5. Kollias G., Douni E., Kassiotis G., Kontoyiannis D. The function of tumor necrosis factor and receptors in models of multi-organ inflammation, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Ann Rheum Dis 1999;58(Suppl 1):132-139.
6. Tilg H., Dinarello C.A., Mier J.W. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 1997;18:428-432.[Medline]
7. Patrick D.A., Moore F.A., Moore E.E., Barnet C.C., Sillimann C.C., Jr The inflammatory profile of inteleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in post-injury multiple organ failure. Am J Surg 1996;172:425-431.[Medline]
8. Wan S., Izzat M.B., Lee T.W., et al. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg 1999;68:52-57.[Abstract/Free Full Text]
9. Krakauer T. IL-10 inhibits the adhesion of leukocytic cells to IL-1-activated human endothelial cells. Immunol Lett 1995;45:61-65.[Medline]
10. Lane J.S., Todd K.E., Lewis M.P., et al. Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion. Surgery 1997;122:288-294.[Medline]
11. Yang Z., Zingarelli B., Szabo C. Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury. Circulation 2000;101:1019-1026.[Abstract/Free Full Text]
12. Chaney M.A. Corticosteroids and cardiopulmonary bypass: a review of clinical investigations. Chest 2002;121:921-931.[Abstract/Free Full Text]
13. Higgins T.L., Estafanous F.G., Loop F.D., Beck G.J., Blum J.M., Paranandi L. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. JAMA 1992;267:2344-2348.[Abstract/Free Full Text]
14. Tassani P. Corticosteroids during operations using cardiopulmonary bypass. J Clin Anesth 2000;12:242-247.[Medline]
15. Buckberg G.D. Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: operative techniques and objectives. J Card Surg 1989;4:216-238.[Medline]
16. Teoh K.H.T., Bradley C.A., Gauldie J., Burrows H. Steroids inhibition of cytokine-mediated vasodilation after warm heart surgery. Circulation 1998;92(Suppl II):347-353.
17. Wan S., LeClaerc J.L., Schmartz D., et al. Hepatic release of interleukin-10 during cardiopulmonary bypass in steroid-pretreated patients. Am Heart J 1997;133:335-339.[Medline]
18. Chaney M.A., Nikolov M.P., Blakeman B., Bakhos M., Slogoff S. Pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation. Anesth Analg 1998;87:27-33.[Abstract/Free Full Text]
19. Asimakopoulos G., Smith P.L.C., Ratnatunga C.P., Taylor K.M. Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass. Ann Thorac Surg 1999;68:1107-1115.[Abstract/Free Full Text]
20. El Azab S.R., Rosseel P.M.J., De Lange J.J., et al. Dexamethasone decrease the pro- to anti-inflammatory cytokine ratio during cardiac surgery. Br J Anaesth 2002;88:496-501.[Abstract/Free Full Text]
21. Haring F., Cesnjevar R., Mahmoud F.O., von der Emde J. Perioperative factors influencing interleukin-10 release under cardiopulmonary bypass. Thorac Cardiovasc Surg 1999;47:361-368.[Medline]
22. Nathan N., Preux P.M., Feiss P., Denizot Y. Plasma interleukin-4, interleukin-10, and interleukin-13 concentrations and complications after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000;14:156-160.[Medline]
23. Wei M., Kuukasjarvi P., Laurikka J., et al. Cytokine responses and myocardial injury in coronary artery bypass grafting. Scand J Clin Laboratory Invest 2001;61:161-166.[Medline]
24. Richter JA, Meisner H, Tassani P, et al. Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting. Ann Thorac Surg 1999;69:77–83
25. Paparella D., Yau T.M., Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002;21:232-244.[Abstract/Free Full Text]

This article has been cited by other articles:

				K. M. Ho and J. A. Tan Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery: A Dose-Response Meta-Analysis Circulation, April 14, 2009; 119(14): 1853 - 1866. [Abstract] [Full Text] [PDF]

				M. D. McEvoy, M. J. Sabbagh, A. G. Taylor, J. A. Zavadzkas, C. N. Koval, R. E. Stroud, R. L. Ford, J. E. McLean, S. T. Reeves, R. Mukherjee, et al. Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model Anesth. Analg., February 1, 2009; 108(2): 399 - 406. [Abstract] [Full Text] [PDF]

				R. P. Whitlock, S. Chan, P.J. Devereaux, J. Sun, F. D. Rubens, K. Thorlund, and K. H.T. Teoh Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials Eur. Heart J., November 1, 2008; 29(21): 2592 - 2600. [Abstract] [Full Text] [PDF]

				C. S.H. Ng, A. A. Arifi, S. Wan, A. M.H. Ho, I. Y.P. Wan, E. M.C. Wong, and A. P.C. Yim Ventilation During Cardiopulmonary Bypass: Impact on Cytokine Response and Cardiopulmonary Function Ann. Thorac. Surg., January 1, 2008; 85(1): 154 - 162. [Abstract] [Full Text] [PDF]

				O. J. Liakopoulos, J. D. Schmitto, S. Kazmaier, A. Brauer, M. Quintel, F. A. Schoendube, and H. Dorge Cardiopulmonary and Systemic Effects of Methylprednisolone in Patients Undergoing Cardiac Surgery Ann. Thorac. Surg., July 1, 2007; 84(1): 110 - 119. [Abstract] [Full Text] [PDF]

				K. Kaur, A. K. Sharma, and P. K. Singal Significance of changes in TNF-{alpha} and IL-10 levels in the progression of heart failure subsequent to myocardial infarction Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H106 - H113. [Abstract] [Full Text] [PDF]

				C.-H. Hsing, M.-Y. Hsieh, W.-Y. Chen, E. Cheung So, B.-C. Cheng, and M.-S. Chang Induction of Interleukin-19 and Interleukin-22 After Cardiac Surgery With Cardiopulmonary Bypass Ann. Thorac. Surg., June 1, 2006; 81(6): 2196 - 2201. [Abstract] [Full Text] [PDF]

				S. M Romano, S. Scolletta, I. Olivotto, B. Biagioli, G. F. Gensini, M. Chiostri, and P. Giomarelli Systemic arterial waveform analysis and assessment of blood flow during extracorporeal circulation Perfusion, March 1, 2006; 21(2): 109 - 116. [Abstract] [PDF]

				P. Giomarelli, B. Biagioli, and S. Scolletta Cardiac output monitoring by pressure recording analytical method in cardiac surgery Eur. J. Cardiothorac. Surg., September 1, 2004; 26(3): 515 - 520. [Abstract] [Full Text] [PDF]

				J. B. Celik, N. Gormus, S. Okesli, Z. I. Gormus, and H. Solak Methylprednisolone prevents inflammatory reaction occurring during cardiopulmonary bypass: effects on TNF-{alpha}, IL-6, IL-8, IL-10 Perfusion, May 1, 2004; 19(3): 185 - 191. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Online Discussion Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giomarelli, P. Articles by Biagioli, B. Search for Related Content PubMed PubMed Citation Articles by Giomarelli, P. Articles by Biagioli, B. Related Collections Extracorporeal circulation