Bi-ventricular repair; Inflammatory balance; Interleukin-10; Interleukin-12; Interleukin-6; Pediatric cardiac surgery; Procalcitonin; Total cavo-pulmonary connection; Tumor necrosis factor-α; Pediatrics, Perinatology and Child Health; Cell Biology; Molecular Biology; General Medicine
Abstract :
[en] BACKGROUND: To examine whether uni-ventricular palliation (UVP) and bi-ventricular repair (BVR) result in a different pattern of systemic inflammatory response to pediatric cardiac surgery with extra-corporeal circulation (ECC).
METHODS: In 20 children (median age 39.5 months) undergoing either UVP (n = 12) or BVR (n = 8), plasma levels of the inflammatory cytokines TNF-α, IL-6, IL-10, and IL-12 and of procalcitonin (PCT), were measured before, during and after open cardiac surgery up to postoperative day (POD) 10.
RESULTS: Epidemiologic, operative- and outcome variables were similar in both groups but post-operative central venous pressure that was higher in UVP. In the whole cohort, the inflammatory response was characterized by an early important, significant and parallel increase of IL-6 and IL-10 that reached their peak values either at the end of ECC (IL-10) or 4 h postoperatively (IL-6), respectively and by a significant and parallel decrease of TNF-α and IL-12 levels after connection to ECC, followed by a bi-phasic significant increase with a first peak 4 h after ECC and a second at POD 10, respectively. Patients after UVP showed a shift of the cytokine balance with lower IL-6- (p = 0.01) after connection to ECC, lower early post-operative TNF-α - (p = 0.02) and IL-12- (p = 0.04) concentrations and lower TNF-α/IL-10-ratio (p = 0.03) as compared with patients with BVR. Levels of PCT were similar in both groups.
CONCLUSIONS: UVP is associated with an anti-inflammatory shift of the inflammatory response to cardiac surgery that might be related to the particular hemodynamic situation of patients with UVP.
Disciplines :
Pediatrics Cardiovascular & respiratory systems
Author, co-author :
Sigler, Matthias ; Pediatric Cardiology, Intensive Care Medicine and Neonatology, Georg-August Universität, Robert-Koch-Str. 40, D-37075, Göttingen, Germany. msigler@gwdg.de
Rouatbi, Hatem; Department of Pediatrics and Pediatric Cardiology, University Hospital Liège, Liège, Belgium
Vazquez-Jimenez, Jaime; Department of Pediatric Cardiac Surgery, University Hospital Aachen, Aachen, Germany
Hövels-Gürich H, Schumacher K, Vazquez-Jimenez J et al (2002) Cytokine balance in infants undergoing cardiac operation. AnnThorac Surg 73(2):601–608 DOI: 10.1016/S0003-4975(01)03391-4
Hövels-Gürich H, Vazquez-Jimenez J, Silvestri A et al (2002) Production of proinflammatory cytokines and myocardial dysfunction after arterial switch operation in neonates with transposition of the great arteries. J Thorac Cardiovasc Surg 124(4):811–820 DOI: 10.1067/mtc.2002.122308
Seghaye M (2003) The clinical implications of the systemic inflammatory reaction related to cardiac operations in children. Cardiol Young 13(3):228–239 DOI: 10.1017/S1047951103000465
Buchko M, Stewart C, Hatami S, Himmat S, Freed D, Nagendran J (2019) Total parenteral nutrition in ex vivo lung perfusion: addressing metabolism improves both inflammation and oxygenation. American Journal of Transplantation 19(12):3390–3397 DOI: 10.1111/ajt.15572
Rouatbi H, Farhat N, Heying R, Gérard A, Vazquez-Jimenez J, Seghaye M (2020) Right atrial myocardial remodeling in children with atrial septal defect involves inflammation, growth, fibrosis, and apoptosis. Front Pediatr 8:40. 10.3389/fped.2020.00040 DOI: 10.3389/fped.2020.00040
Qing M, Schumacher K, Heise R et al (2003) Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects. J Am Coll Cardiol 41(12):2266–2274 DOI: 10.1016/S0735-1097(03)00477-7
Qing M, Nimmesgern A, Heinrich P et al (2003) Intrahepatic synthesis of tumor necrosis factor-α related to cardiac surgery is inhibited by interleukin-10 via the Janus kinase (Jak)/signal transducers and activator of transcription (STAT) pathway. Crit Care Med 31(12):2769–2775 DOI: 10.1097/01.CCM.0000098858.64868.9C
Glossop J, Cartmell S (2009) Effect of fluid flow-induced shear stress on human mesenchymal stem cells: Differential gene expression of IL1B and MAP 3K8 in MAPK signaling. Gene Expression Patterns 9(5):381–388 DOI: 10.1016/j.gep.2009.01.001
Liu S, Deng X, Zhang P et al (2020) Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines. Cardiovasc Res 116(10):1721–1732 DOI: 10.1093/cvr/cvz262
Nakajima H, Mochizuki N (2017) Flow pattern-dependent endothelial cell responses through transcriptional regulation. Cell Cycle 16(20):1893–1901 DOI: 10.1080/15384101.2017.1364324
Lommi J, Pulkki K, Koskinen P et al (1997) Haemodynamic, neuroendocrine and metabolic correlates of circulating cytokine concentrations in congestive heart failure. Eur Heart J 18(10):1620–1625 DOI: 10.1093/oxfordjournals.eurheartj.a015142
Sedger L, McDermott M (2014) TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants – past, present and future. Cytokine Growth Factor Rev 25(4):453–472 DOI: 10.1016/j.cytogfr.2014.07.016
Sun L, He C, Nair L, Yeung J, Egwuagu C (2015) Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease. Cytokine 75(2):249–255 DOI: 10.1016/j.cyto.2015.01.030
Tanaka T, Narazaki M, Kishimoto T (2014) IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6(10):a016295–a016295 DOI: 10.1101/cshperspect.a016295
Walter M (2014) The molecular basis of IL-10 function: from receptor structure to the onset of signaling. Curr Top Microbiol Immunol 380:191–212
Goswami B, Rajappa M, Mallika V, Shukla D, Kumar S (2009) TNF-α/IL-10 ratio and C-reactive protein as markers of the inflammatory response in CAD-prone North Indian patients with acute myocardial infarction. Clinica Chimica Acta 408(1-2):14–18 DOI: 10.1016/j.cca.2009.06.029
Luo Y, Zheng SG (2016) Hall of fame among pro-inflammatory cytokines: Interleukin-6 gene and its transcriptional regulation mechanisms. Front Immunol 7:604. 10.3389/fimmu.2016.00604 DOI: 10.3389/fimmu.2016.00604
Groth A, Vrugt B, Brock M, Speich R, Ulrich S, Huber LC (2014) Inflammatory cytokines in pulmonary hypertension. Respir Res 15(1):47. 10.1186/1465-9921-15-47 DOI: 10.1186/1465-9921-15-47
Murray PJ (2007) The JAK-STAT signaling pathway: input and output integration. J Immunol 178(5):2623–2629 DOI: 10.4049/jimmunol.178.5.2623
Dangers M, Kiyan J, Grote K, Schieffer B, Haller H, Dumler I (2010) Mechanical stress modulates SOCS-1 expression in human vascular smooth muscle cells. J Vasc Res 47(5):432–440 DOI: 10.1159/000281583
Franke A, Lante W, Kurig E, Zöller LG, Weinhold C, Markewitz A (2006) Is interferon gamma suppression after cardiac surgery caused by a decreased interleukin-12 synthesis? Ann Thorac Surg 82(1):103–109 DOI: 10.1016/j.athoracsur.2006.02.042
Justus G, Walker C, Rosenthal L-M, Berger F, Miera O, Schmitt KRL (2019) Immunodepression after CPB: cytokine dynamics and clinics after pediatric cardiac surgery - a prospective trial. Cytokine 122:154018. 10.1016/j.cyto.2017.03.017 DOI: 10.1016/j.cyto.2017.03.017
De Angelis E, Pecoraro M, Rusciano MR, Ciccarelli M, Popolo A (2019) Cross-talk between neurohormonal pathways and the immune system in heart failure: a review of the literature. Int J Mol Sci 20(7):1698. 10.3390/ijms20071698 DOI: 10.3390/ijms20071698
Bronicki RA, Backer CL, Baden HP, Mavroudis C, Crawford SE, Green TP (2000) Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg 69(5):1490–1495 DOI: 10.1016/S0003-4975(00)01082-1
Heying R, Wehage E, Schumacher K et al (2012) Dexamethasone pretreatment provides antiinflammatory and myocardial protection in neonatal arterial switch operation. Ann Thorac Surg 93(3):869–876 DOI: 10.1016/j.athoracsur.2011.11.059
Brocca A, Virzì GM, de Cal M, Giavarina D, Carta M, Ronco C (2017) Elevated levels of procalcitonin and interleukin-6 are linked with postoperative complications in cardiac surgery. Scand J Surg 106(4):318–324 DOI: 10.1177/1457496916683096
Seghaye MC, Grabitz RG, Duchateau J et al (1996) Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. J Thorac Cardiovasc Surg 112(3):687–697 DOI: 10.1016/S0022-5223(96)70053-3
Tsurumi A, Que Y-A, Ryan CM, Tompkins RG, Rahme LG (2016) TNF-α/IL-10 ratio correlates with burn severity and may serve as a risk predictor of increased susceptibility to infections. Front Public Health 4:216. 10.3389/fpubh.2016.00216 DOI: 10.3389/fpubh.2016.00216
Zorzanelli L, Maeda NY, Clavé MM, Aiello VD, Rabinovitch M, Lopes AA (2016) Serum cytokines in young pediatric patients with congenital cardiac shunts and altered pulmonary hemodynamics. Mediators Inflamm 2016:7672048 DOI: 10.1155/2016/7672048
Chiu J-J, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91(1):327–387 DOI: 10.1152/physrev.00047.2009
Demicheva E, Hecker M, Korff T (2008) Stretch-induced activation of the transcription factor activator protein-1 controls monocyte chemoattractant protein-1 expression during arteriogenesis. Circ Res 103(5):477–484 DOI: 10.1161/CIRCRESAHA.108.177782
Li M, Tan Y, Stenmark KR, Tan W (2013) High pulsatility flow induces acute endothelial inflammation through overpolarizing cells to activate NF-κB. Cardiovasc Eng Technol 4(1):26–38 DOI: 10.1007/s13239-012-0115-5
Sundareswaran KS, Haggerty CM, de Zélicourt D et al (2012) Visualization of flow structures in Fontan patients using 3-dimensional phase contrast magnetic resonance imaging. J Thorac Cardiovasc Surg 143(5):1108–1116 DOI: 10.1016/j.jtcvs.2011.09.067
Bartekova M, Radosinska J, Jelemensky M, Dhalla NS (2018) Role of cytokines and inflammation in heart function during health and disease. Heart Fail Rev 23(5):733–758 DOI: 10.1007/s10741-018-9716-x
