EJCTS Click here to go to Siemens website
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Mizuho Imamaki
Hitoshi Shimura
Hiroki Kohno
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishida, K.
Right arrow Articles by Miyazaki, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishida, K.
Right arrow Articles by Miyazaki, M.
Related Collections
Right arrow Cardiac - other

Eur J Cardiothorac Surg 2006;29:501-505
© 2006 Elsevier Science NL

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting

Keiichi Ishida * , Fumio Kimura, Mizuho Imamaki, Atsushi Ishida, Hitoshi Shimura, Hiroki Kohno, Manabu Sakurai, Masaru Miyazaki

Department of General Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1 Chuo-ku, Chiba 260-0856, Japan

Received 29 September 2005; received in revised form 19 December 2005; accepted 21 December 2005.

* Corresponding author. Tel.: +81 43 226 2103; fax: +81 43 226 2552. (Email: keiichi-ishida{at}pro.odn.ne.jp).


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 
Objective: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. Methods: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6 h thereafter, and on postoperative days (POD) 1–4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. Results: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70 ± 6.4 years vs 60 ± 8.8 years, P = 0.001); however, there was no difference in other pre- and perioperative variables. TNF-{alpha} level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6 h after the completion of anastomoses. IL-6 levels of 3 and 6 h after anastomoses were significantly higher in patients with postoperative AF (360 ± 143 pg/ml vs 230 ± 94 pg/ml, P = 0.0047, 435 ± 175 pg/ml vs 247 ± 102 pg/ml, P = 0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06–54.9; P = 0.04) and age (odds ratio 1.18; 95% CI, 1.01–1.39; P = 0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r = 0.04, P = 0.01, and r = 0.47, P = 0.04, respectively). Conclusions: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.

Key Words: Arrhythmia • Coronary artery bypass grafts • Inflammation


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 References
 
Atrial fibrillation (AF) is the most frequent arrhythmic complication after coronary artery bypass grafting (CABG), with the incidence ranging from 25 to 35% [1]. Although several risk factors for postoperative AF have been elucidated [1], the mechanism by which postoperative AF develops is not entirely clear. A systemic inflammatory response caused by cardiopulmonary bypass (CPB) is known to be associated with the pathogenesis of postoperative AF [2,3]. Avoidance of CPB may result in lowering the incidence of postoperative AF [4]; however, similar incidence of postoperative AF between patients with and without CPB has been also reported [5,6]. Moreover, surgical trauma in CABG contributes postoperative inflammatory response to a higher degree than CPB [7]. Thus, it is suggested that inflammation participates in the pathogenesis of postoperative AF in patients undergoing off-pump CABG.

Proinflammatory cytokines, such as tumor necrosis factor (TNF)-{alpha}, IL-6, and IL-8, play a pivotal role in the upstream of inflammatory cascade. TNF-{alpha} stimulates the secretion of other proinflammatory cytokines including IL-6 and IL-8 [8]. IL-6 is a multifunctional proinflammatory cytokine, which also plays an important role in ischemia–reperfusion injury [9]. IL-8 attributes neutrophil migration and activation, which results in neutrophil-mediated organ injury [8]. However, association between these proinflammatory cytokines, which are induced by cardiac surgery, and postoperative AF has not been well evaluated, especially in patients undergoing off-pump CABG. We evaluated inflammatory cytokines after off-pump CABG and examined its relation to the occurrence of postoperative AF.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 References
 
2.1 Patients
Thirty-nine consecutive patients with coronary artery disease undergoing elective CABG at the Chiba University Hospital were enrolled in this study. Off-pump technique was attempted initially in all cases scheduled for elective CABG. Patients with preoperative AF, those with chronic renal failure requiring hemodialysis, those receiving preoperative administration of steroids, and those who had to be converted to a standard on-pump procedure were excluded. The study was approved by the institutional ethics committee and written informed consent was obtained from all cases.

2.2 Anesthesia and surgical technique
Anesthesia was induced and maintained by intravenous infusion of sufentanyl citrate and propofol, and inhalation of isoflurane. Muscle relaxation was achieved with vecuronium bromide. Heparin (150 U/kg) was administered as an anticoagulant, and was neutralized by protamine after completion of anastomoses. All patients underwent a median sternotomy. The internal thoracic artery was harvested by a skeltonized technique, using ultrasonic scalpel. In cases with severe left main trunk disease (≥90%) or severe left ventricle dysfunction (ejection fraction ≤30%), intra-aortic balloon pump (IABP) was initiated before the procedure. If necessary, the radial artery, right gastroepiploic artery, or saphenous vein were harvested. Octopus 4 (Octopus tissue stabilization system, Medtronic Inc, Minneapolis, MN, USA) was used to stabilize the target coronary vessel in all cases. In the majority of the cases, the left anterior descending artery (LAD) was revascularized first. The target vessel was exposed and snared above the anastomotic site by using a 4-0 polypropylene suture with felt. The coronary artery was then opened, and anastomosis was performed with an 8-0 polypropylene suture. Further distal anastomoses were performed using the same myocardial coronary artery stabilizer system. Intracoronary shunt was used in anastomosis of the LAD or proximal right coronary artery. Visualization was enhanced by the use of a surgical blower-humidifier.

2.3 Measurements
Samples were collected in bottles containing EDTA from each patient, on anesthetic induction, after sternotomy before anastomosis, at the completion of anastomoses before protamine infusion, 3 and 6 h thereafter, and on postoperative days (POD) 1–4. Samples were immediately centrifuged (3000 x g for 5 min) and plasma was stored in aliquots at –80 °C until assay. Levels of TNF-{alpha}, IL-6 and IL-8 were determined by means of commercially available enzyme-linked immunosorbent assays (R & D Systems, Minneapolis, MN, USA) in accordance with the manufacturer's instructions. Serum levels of CRP were also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. Sensitivities of TNF-{alpha}, IL-6, IL-8, and CRP were 0.12 pg/ml, 0.70 pg/ml, 3.5 pg/ml, and 0.1 mg/dl, respectively.

2.4 Definition of AF
Postoperatively, heart rate and rhythm were continuously monitored until POD 7. In the present study, postoperative AF was defined as the characteristic arrhythmia lasting for greater double equals5 min and confirmed by 12-leads ECG. Magnesium sulfate was administered in all cases, from the end of surgery to POD 3, as a prophylaxis against postoperative AF. However, ß-blockers were not routinely used postoperatively.

2.5 Statistical analysis
Continuous variables of clinical parameters were reported as mean ± SD and compared using the Mann–Whitney U-test. Discrete variables were reported as frequencies and percentages and analyzed using the chi-square or Fisher's exact test as appropriate. A value of P < 0.05 was considered to be statistically significant. The distribution of cytokines and CRP levels were highly skewed, and data were thus logarithmically transformed before analysis, although untransformed data are shown (presented as mean ± SD). Analysis of variance for repeated measures was used for comparison of cytokines and CRP levels between the two groups at each time. After using the Bonferroni correction, we defined P < 0.0056 as statistically significant. To assess the association of cytokine level and postoperative AF, logistic regression analysis was used including clinically significant factors (P < 0.1) and all factors with P < 0.05. Correlations between cytokine levels and other continuous variables were assessed using Spearman's rank correlation. A value of P < 0.05 was considered to be statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 References
 
Thirty-nine patients were included in this study, and 11 patients (28%) developed AF postoperatively (three patients on POD 1, one patient on POD 2, two patients on POD 3, two patients on POD 4, two patients on POD 6, and one patient on POD 7). All patients survived the procedure and had a normal recovery, although one patient with postoperative AF required surgical exploration for cardiac tamponade that developed on POD 2.

3.1 Patient characteristics and perioperative data
Patient characteristics and perioperative data are shown in Table 1 . Patients who developed postoperative AF were significantly older, and tended to have triple vessel disease more frequently than those who did not; however, the number of distal anastomoses performed were similar between the groups. Although operative time and the number of distal anastomoses were similar between the groups, intraoperative blood loss was slightly higher in patients with postoperative AF than in those without. Time to extubation in patients with postoperative AF was longer than that in patients without; however, pulmonary dysfunction requiring ventilation support more than 24 h occurred in only one patient with sleep apnea syndrome, who developed postoperative AF.


View this table:
[in this window]
[in a new window]
  		Table 1. Patient characteristics and perioperative data
 
3.2 Inflammatory markers
Fig. 1 shows inflammatory markers, including TNF-{alpha}, IL-6, IL-8, and CRP. TNF-{alpha} did not elevate during the study period, and there was no difference between the two groups. IL-6 increased after the completion of anastomoses, peaked at 6 h, and declined thereafter. Plasma levels of IL-6 were significantly higher in patients with postoperative AF than in those without, at 3 and 6 h after completion of anastomoses (360 ± 143 pg/ml vs 230 ± 94 pg/ml, P = 0.0047, 435 ± 175 pg/ml vs 247 ± 102 pg/ml, P = 0.0005, respectively). IL-8 was significantly elevated after completion of anastomosis with a peak at 3 h after the procedure, and declined thereafter. Patients with postoperative AF had higher levels of IL-8 after the surgery than those without, although no statistically significant difference was seen. CRP also significantly elevated after the surgery, and peaked on POD 2. However, no significant difference between the two groups was observed during the study period.


Figure 1
View larger version (20K):
[in this window]
[in a new window]
  		Fig. 1. Plasma levels of TNF-{alpha}, IL-6, and IL-8, and serum levels of CRP in patients with (\#9632;) and without ({circ}) AF. Values are given as mean ± SD. * P < 0.0056 versus non-AF patients. Pre: preoperative; BA: before anastomoses; AA: after anastomoses; 3 h and 6 h: time points after completion of anastomoses; POD: postoperative day.

 
3.3 Association between IL-6 and postoperative AF
To assess association between IL-6 and postoperative AF, maximum level of IL-6 immediately after the surgery was categorized into quartiles, and the highest quartile (>401 pg/ml) was compared to the combination of the other quartiles. Logistic regression analysis in a model that included age, triple vessel disease, and IL-6 demonstrated that the highest quartile of IL-6 level and age was significantly associated with the development of postoperative AF (Table 2 ).


View this table:
[in this window]
[in a new window]
  		Table 2. Logistic regression for postoperative AF
 
3.4 Correlations of IL-6 and other variables
Furthermore, correlations of maximum level of IL-6 immediately after the surgery (as a continuous value) and other clinical variables were assessed. Among clinical variables shown in Table 1, Spearman's analysis revealed that the IL-6 level positively correlated to age and intraoperative blood loss (r = 0.04, P = 0.01, and r = 0.47, P = 0.04, respectively). Regarding to correlations of the IL-6 level to other inflammatory markers, IL-8 level at 6 h after the anastomoses positively correlated to the IL-6 level (r = 0.32, P = 0.045); however, no relationship between CRP levels after the surgery and the IL-6 level was found.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
References
 
The incidence of AF after off-pump CABG reportedly ranges from 12.9 to 26.4% [4–6]. Our incidence of postoperative AF in patients undergoing off-pump CABG was 28%, which may be slightly higher than the previous results. This might be because the incidence of postoperative AF depends on its definition, and modality of diagnosis.

Advanced age has been consistently reported as a risk factor for postoperative AF [10,11], possibly because older patients have atrial structural changes affecting susceptibility to postoperative AF [12]. In the present study, patients with postoperative AF were 10 years older than those without, and logistic regression analysis revealed that age was significantly associated with the development postoperative AF. Thus, in agreement with the previous results, it was considered that advanced age is a major risk factor for AF after off-pump CABG.

The present study evaluated proinflammatory cytokines in patients undergoing off-pump CABG. TNF-{alpha} level did not change significantly during the study period, possibly because systemic level of TNF-{alpha} may not reflect its local concentration in the myocardium, which is a major source of TNF-{alpha} after reperfusion [13]. Plasma level of IL-8 significantly increased after the surgery and was higher after the surgery in patients with postoperative AF compared with those without, although there was no statistically significant difference. IL-8, which is induced after reperfusion of ischemic myocardium, attracts and activates neutrophils, resulting in lung injury associated with pulmonary leukocyte sequestration following CPB [8]. In the present study, time to extubation tended to be longer in patients with postoperative AF than those without. However, pulmonary dysfunction, which is reportedly associated with postoperative AF [1], occurred in only one patient with sleep apnea syndrome; moreover, most of our patients extubated within 24 h after the surgery. Thus, other factors than pulmonary dysfunction, such as delayed awakening after the surgery, may have an influence on time to extubation.

Plasma levels of IL-6 elevated immediately after the surgery and were higher in patients with postoperative AF compared with those without. It has been revealed that the release of IL-6 is induced by reperfusion of ischemic myocardium, surgical trauma, and CPB [7,9]. In the present study, the number of distal bypass graft was similar between the groups, while patients with postoperative AF were more likely to have triple vessel disease than those without. However, our result did not reveal whether reperfusion of ischemic myocardium induced the release of IL-6, although its attribution to the release of IL-6 may be less than surgical trauma [7]. Our result that intraoperative blood loss positively correlated to the maximum level of IL-6 suggested that surgical trauma mainly induced the release of IL-6 after off-pump CABG. Furthermore, it has been reported that polymorphism of the promoter of the IL-6 gene have an influence on plasma level of IL-6 after CABG [14,15]. On the basis of the result that IL-6 level after the surgery also correlated positively to age, it was suggested that advanced age may modulate the elevation of IL-6, since aging affects inflammatory response following stimulation [16].

It has been revealed that complement-CRP complex 2 days after CPB surgery is associated with the occurrence of postoperative AF, although CRP level was not [2]. In agreement with the previous result, we had no significant difference in CRP level between the groups, although CRP significantly increased after the surgery, 50-fold from preoperatively. IL-6 is known to induce the production of acute phase proteins, and was higher in patients with postoperative AF than those without; however, the present study revealed no correlation between IL-6 and CRP levels, which may have been caused by differences in clearance rates [2].

In logistic regression analysis, higher level of IL-6 as well as age was significantly associated with postoperative AF. Our results are concordant with the previous result that a specific IL-6 promoter gene variant modulates postoperative IL-6 level and is related to the development of postoperative AF [14]. Administration of glucocoticoids such as methylprednisolone and dexamethasone, which significantly reduces plasma level of IL-6, can reduce incidence of AF after on-pump CABG [17,18]. Thus, it is suggested that IL-6 is associated with the development of postoperative AF. IL-6 regulates a large variety of cellular response in multiple organ systems, besides, endocrine responses and central nervous system [19,20]. IL-6, like TNF-{alpha} and IL-1ß, has a stimulatory effect on the hypothalamo-pituitary-adrenal (HPA) axis, increasing hypothalamic secretion of corticotropin-releasing hormone (CRH) [21]. CRH subsequently increases secretion of adrenocorticotropin hormone (ACTH) and cortisol. Furthermore, CRH stimulates noradrenergic neurons of the central nervous system, which induces the release of norepinephrine. Subcutaneous administration of IL-6 induces significant increases in plasma levels of ACTH, cortisol, and norepinephrine [22]. Thus, IL-6 not only is a marker of severity of inflammation but also regulates inflammatory response and activates the sympathetic nervous system, which is associated with occurrence of postoperative AF in vulnerable patients [23,24].

Postoperative AF usually occurs within the first postoperative week, and mostly on postoperative days 2–4 [1]. In the present study, postoperative AF occurred within the first four postoperative days in 8 of 11 patients. However, only three patients developed postoperative AF on POD 1, while IL-6 level peaked at 6 h after anastomoses. The discrepancy in the time when IL-6 level peaked and postoperative AF occurred may be explained by association between IL-6 and subsequent sympathetic nerve activation.

In conclusion, advanced age is a major risk factor for the development of postoperative AF, and moreover, a higher degree of systemic inflammatory response, which is induced by surgical trauma, is also associated with the development of AF after off-pump CABG. The mechanism by which systemic inflammatory response to surgical trauma causes postoperative AF remains to be further elucidated.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 References
 

  1. Maisel WH, Rawn JD, Stevenson WG. Atrial fibrillation after cardiac surgery. Ann Intern Med 2001;135:1061-1073.[Abstract/Free Full Text]
  2. Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt FW, de Beaumont EM, Wildevuur CR, Eijsman L, Trouwborst A, Hack CE. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 1997;96:3542-3548.[Abstract/Free Full Text]
  3. Abdelhadi RH, Gurm HS, Van Wagoner DR, Chung MK. Relation of an exaggerated rise in white blood cells after coronary bypass or cardiac valve surgery to development of atrial fibrillation postoperatively. Am J Cardiol 2004;93:1176-1178.[CrossRef][Medline]
  4. Calafiore AM, Di Mauro M, Canosa C, Di Giammarco G, Iaco AL, Contini M. Myocardial revascularization with and without cardiopulmonary bypass: advantages, disadvantages and similarities. Eur J Cardiothorac Surg 2003;24:953-960.[Abstract/Free Full Text]
  5. Puskas JD, Williams WH, Duke PG, Staples JR, Glas KE, Marshall JJ, Leimbach M, Huber P, Garas S, Sammons BH, McCall SA, Petersen RJ, Bailey DE, Chu H, Mahoney EM, Weintraub WS, Guyton RA. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:797-808.[Abstract/Free Full Text]
  6. Karthik S, Musleh G, Grayson AD, Keenan DJ, Hasan R, Pullan DM, Dihmis WC, Fabri BM. Effect of avoiding cardiopulmonary bypass in non-elective coronary artery bypass surgery: a propensity score analysis. Eur J Cardiothorac Surg 2003;24:66-71.[Abstract/Free Full Text]
  7. Prondzinsky R, Knupfer A, Loppnow H, Redling F, Lehmann DW, Stabenow I, Witthaut R, Unverzagt S, Radke J, Zerkowski HR, Werdan K. Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass. J Thorac Cardiovasc Surg 2005;129:760-766.[Abstract/Free Full Text]
  8. Wan S, Yim AP. Cytokines in myocardial injury: impact on cardiac surgical approach. Eur J Cardiothorac Surg 1999;16(Suppl. 1):S107-S111.[Abstract/Free Full Text]
  9. Sawa Y, Ichikawa H, Kagisaki K, Ohata T, Matsuda H. Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium. J Thorac Cardiovasc Surg 1998;116:511-517.[Abstract/Free Full Text]
  10. Zaman AG, Archbold RA, Helft G, Paul EA, Curzen NP, Mills PG. Atrial fibrillation after coronary artery bypass surgery: a model for preoperative risk stratification. Circulation 2000;101:1403-1408.[Abstract/Free Full Text]
  11. Leitch JW, Thomson D, Baird DK, Harris PJ. The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1990;100:338-342.[Abstract]
  12. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993;56:539-549.[Abstract]
  13. Wan S, Izzat MB, Lee TW, Wan IY, Tang NL, Yim AP. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg 1999;68:52-56discussion 56–7.[Abstract/Free Full Text]
  14. Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati MB, Schiavello R, Maseri A, Possati G. The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication?. Circulation 2003;108(Suppl. 1):II195-II199.
  15. Burzotta F, Iacoviello L, Di Castelnuovo A, Glieca F, Luciani N, Zamparelli R, Schiavello R, Donati MB, Maseri A, Possati G, Andreotti F. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am J Cardiol 2001;88:1125-1128.[CrossRef][Medline]
  16. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 2004;39:687-699.[CrossRef][Medline]
  17. Yared JP, Starr NJ, Torres FK, Bashour CA, Bourdakos G, Piedmonte M, Michener JA, Davis JA, Rosenberger TE. Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery. Ann Thorac Surg 2000;69:1420-1424.[Abstract/Free Full Text]
  18. Rubens FD, Nathan H, Labow R, Williams KS, Wozny D, Karsh J, Ruel M, Mesana T. Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass. Ann Thorac Surg 2005;79:655-665.[Abstract/Free Full Text]
  19. Woiciechowsky C, Schoning B, Lanksch WR, Volk HD, Docke WD. Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med 1999;77:769-780.[CrossRef][Medline]
  20. Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 1998;128:127-137.[Abstract/Free Full Text]
  21. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993;77:1690-1694.[Abstract]
  22. Stouthard JM, Romijn JA, Van der Poll T, Endert E, Klein S, Bakker PJ, Veenhof CH, Sauerwein HP. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol 1995;268:E813-E819.
  23. Kalman JM, Munawar M, Howes LG, Louis WJ, Buxton BF, Gutteridge G, Tonkin AM. Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60:1709-1715.[Abstract/Free Full Text]
  24. Dimmer C, Tavernier R, Gjorgov N, Van Nooten G, Clement DL, Jordaens L. Variations of autonomic tone preceding onset of atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 1998;82:22-25.[Medline]



This article has been cited by other articles:


Home page
 EuropaceHome page
I. Liuba, H. Ahlmroth, L. Jonasson, A. Englund, A. Jonsson, K. Safstrom, and H. Walfridsson
Source of inflammatory markers in patients with atrial fibrillation
Europace, July 1, 2008; 10(7): 848 - 853.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
K. I. Paraskevas
Applications of statins in cardiothoracic surgery: more than just lipid-lowering
Eur. J. Cardiothorac. Surg., March 1, 2008; 33(3): 377 - 390.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
M. Pretorius, B. S. Donahue, C. Yu, J. P. Greelish, D. M. Roden, and N. J. Brown
Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass
Circulation, September 11, 2007; 116(11_suppl): I-1 - I-7.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
R. B. Neuman, H. L. Bloom, I. Shukrullah, L. A. Darrow, D. Kleinbaum, D. P. Jones, and S. C. Dudley Jr
Oxidative Stress Markers Are Associated with Persistent Atrial Fibrillation
Clin. Chem., September 1, 2007; 53(9): 1652 - 1657.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
V. B. O'Leary, A. E. Jorett, C. M. Marchetti, F. Gonzalez, S. A. Phillips, T. P. Ciaraldi, and J. P. Kirwan
Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults
Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E421 - E427.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
J. Halonen, P. Halonen, O. Jarvinen, P. Taskinen, T. Auvinen, M. Tarkka, M. Hippelainen, T. Juvonen, J. Hartikainen, and T. Hakala
Corticosteroids for the Prevention of Atrial Fibrillation After Cardiac Surgery: A Randomized Controlled Trial
JAMA, April 11, 2007; 297(14): 1562 - 1567.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Mizuho Imamaki
Hitoshi Shimura
Hiroki Kohno
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishida, K.
Right arrow Articles by Miyazaki, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishida, K.
Right arrow Articles by Miyazaki, M.
Related Collections
Right arrow Cardiac - other

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS