Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs

Document Type : Original Article

Authors

1 Department of Anesthesiology, Airforce General Hospital, Beijing 100142, China

2 Department of Anesthesiology, the Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, China

3 Department of Extracorporeal Circulation, the Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, China

Abstract

Objective(s): To study the effect of cardiopulmonary bypass (CPB) on nuclear factor-kappa B (NF-кB) and cytokine expression and pulmonary function in dogs.
Materials and Methods: Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated.
Results: The activity of NF-кB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar–arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M.
Conclusion: CPB can significantly enhance the activation of NF-кB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-кB activation, thus inhibiting the release of cytokines and protecting the lung function.

Keywords

References

1.Apostolakis E, Filos KS, Koletsis E, Dougenis D. Lung dysfunction following cardiopulmonary bypass. J Card Surg 2010; 25:47-55.
2.Onorati F, Rubino AS, Nucera S, Foti D, Sica V, Santini F, et al. Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response. Eur J Cardiothorac Surg 2010; 37:897-904.
3.Ng CS, Hui CW, Wan S, Wan IY, Ho AM, Lau KM, et al. Lung ischaemia-reperfusion induced gene expression. Eur J Cardiothorac Surg 2010; 37:1411-1420.
4.Larsen BM, Goonewardene LA, Joffe AR, Van Aerde JE, Field CJ, Olstad DL, et al. Pre-treatment with an intravenous lipid emulsion containing fish oil (eicosapentaenoic and docosahexaenoic acid) decreases inflammatory markers after open-heart surgery in infants: a randomized, controlled trial. Clin Nutr 2012; 31:322-329.
5.Pearl JM, Schwartz SM, Nelson DP, Wagner CJ, Lyons JM, Bauer SM, et al. Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest. Ann Thorac Surg 2004; 77:994-1000.
6.Ng CS, Arifi AA, Wan S, Ho AM, Wan IY, Wong EM, et al. Ventilation during cardiopulmonary bypass: impact on cytokine response and cardiopulmonary function. Ann Thorac Surg 2008; 85:154-162.
7.Goebel U, Siepe M, Mecklenburg A, Doenst T, Beyersdorf F, Loop T, et al. Reduced pulmonary inflammatory response during cardiopulmonary bypass: effects of combined pulmonary perfusion and carbon monoxide inhalation. Eur J Cardiothorac Surg 2008; 34:1165-1172.
8.Onorati F, Santarpino G, Tangredi G, Palmieri G, Rubino AS, Foti D, et al. Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass. Eur J Cardiothorac Surg 2009; 35:1012-1019.
9.Onorati F, Santini F, Mariscalco G, Bertolini P, Sala A, Faggian G, et al. Leukocyte filtration ameliorates the inflammatory response in patients with mild to moderate lung dysfunction. Ann Thorac Surg 2011; 92:111-121.
10.Mangoush O, Purkayastha S, Haj-Yahia S, Kinross J, Hayward M, Bartolozzi F, et al. Heparin-bonded circuits versus nonheparin-bonded circuits: an evaluation of their effect on clinical outcomes. Eur J Cardiothorac Surg 2007; 31:1058-1069.
11.Gunaydin S, McCusker K, Sari T, Onur MA, Zorlutuna Y. Clinical performance and biocompatibility of hyaluronan-based heparin-bonded extracorporeal circuits in different risk cohorts. Interact Cardiovasc Thorac Surg 2010; 10:371-376.
12.Al-Ruzzeh S, Ambler G, Asimakopoulos G, Omar RZ, Hasan R, Fabri B, et al. Off-pump coronary artery bypass (OPCAB) surgery reduces risk-stratified morbidity and mortality: a United Kingdom Multi-Center Comparative Analysis of Early Clinical Outcome. Circulation 2003; 108:II1-8.
13.Liu SF, Malik AB. NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 2006; 290:L622-645.
14.Srivastava SK, Ramana KV. Focus on molecules: nuclear factor-kappaB. Exp Eye Res 2009; 88:2-3.
15.Baldwin AS Jr. The NF-kappa B I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996; 14:649-683.
16.Deryckere F, Gannon F. A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. Biotechniques 1994; 16:405.
17.Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg 2013; 95:1122-1129.
18.Weissman C. Pulmonary complications after cardiac surgery. Semin Cardiothorac Vasc Anesth 2004; 8:185-211.
19.Ovrum E, Mollnes TE, Fosse E, Holen EA, Tangen G, Abdelnoor M, et al. Complement and granulocyte activation in two different types of heparinized extracorporeal circuits. J Thorac Cardiovasc Surg 1995; 110:1623-1632.
20.Kirklin JK, Chenoweth DE, Naftel DC, Blackstone EH, Kirklin JW, Bitran DD, et al. Effects of protamine administration after cardiopulmonary bypass on complement, blood elements, and the hemodynamic state. Ann Thorac Surg 1986; 41:193-199.
21.Shastri KA, Logue GL, Stern MP, Rehman S, Raza S. Complement activation by heparin-protamine complexes during cardiopulmonary bypass: effect of C4A null allele. J Thorac Cardiovasc Surg 1997; 114:482-488.
22.Khabar KS, elBarbary MA, Khouqeer F, Devol E, al-Gain S, al-Halees Z. Circulating endotoxin and cytokines after cardiopulmonary bypass: differential correlation with duration of bypass and systemic inflammatory response/multiple organ dysfunction syndromes. Clin Immunol Immunopathol 1997; 85:97-103.
23.Clark SC. Lung injury after cardiopulmonary bypass. Perfusion 2006; 21:225-228.
24.Zhou X, Dai Q, Huang X. Neutrophils in acute lung injury. Front Biosci (Landmark Ed) 2012; 17:2278-2283.
25.McKay LI, Cidlowski JA. Cross-talk between nuclear factor-kappa B and the steroid hormone receptors: mechanisms of mutual antagonism. Mol Endocrinol 1998; 12:45-56.
26.Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 1995; 270:286-290.
27.McKay LI, Cidlowski JA. CBP (CREB binding protein) integrates NF-kappaB (nuclear factor-kappaB) and glucocorticoid receptor physical interactions and antagonism. Mol Endocrinol 2000; 14:1222-1234.
28.De Bosscher K, Vanden Berghe W, Haegeman G. The interplay between the glucocorticoid receptor and  nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev 2003; 24:488-422.
29.Lodge AJ, Chai PJ, Daggett CW, Ungerleider RM, Jaggers J. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important. J Thorac Cardiovasc Surg 1999; 117:515-522.
30.Yuan SM. Postperfusion lung syndrome: physio-pathology and therapeutic options. Rev Bras Cir Cardiovasc 2014; 29:414-425.
31.Apostolakis EE, Koletsis EN, Baikoussis NG, Siminelakis SN, Papadopoulos GS.  Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg 2010; 5:1-9.
32.Kiessling AH, Guo FW, Gökdemir Y, Thudt M, Reyher C, Scherer M, et al. The influence of selective pulmonary perfusion on the inflammatory response and clinical outcome of patients with chronic obstructive pulmonary disease undergoing cardiopulmonary bypass. Interact Cardiovasc Thorac Surg 2014; 18:732-739.
33.Torina AG, Silveira-Filho LM, Vilarinho KA, Eghtesady P, Oliveira PP, Sposito AC, et al. Use of modified ultrafiltration in adults undergoing coronary artery bypass grafting is associated with inflammatory modulation and less postoperative blood loss: a randomized and controlled study. Thorac Cardiovasc Surg 2012; 144:663-670.
34.Curtis N, Vohra HA, Ohri SK. Mini extracorporeal circuit cardiopulmonary bypass system: a review. Perfusion 2010; 25:115-124.
35.Tassani P, Richter JA, Barankay A, Braun SL, Haehnel C, et al. Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures? J Cardiothorac Vasc Anesth 1999; 13:165-172.
36.Chaney MA, Durazo-Arvizu RA, Nikolov MP, Blakeman BP, Bakhos M. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. Thorac Cardiovasc Surg 2001; 121:561-569.
 
Iranian Journal of Basic Medical Sciences
Volume 18, Issue 12 - Serial Number 12
December 2015
Pages 1233-1239

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