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Published in: Critical Care 2/2006

Open Access 01-04-2006 | Research

Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: a prospective observational study

Authors: Hugo Tannus Furtado de Mendonça-Filho, Kelly Cristina Pereira, Mariane Fontes, Daniel Augusto de Souza Aranha Vieira, Maria Lucia A Furtado de Mendonça, Luiz Antonio de Almeida Campos, Hugo Caire Castro-Faria-Neto

Published in: Critical Care | Issue 2/2006

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Abstract

Introduction

Cardiovascular surgery with cardiopulmonary bypass (CPB) has improved in past decades, but inflammatory activation in this setting is still unpredictable and is associated with several postoperative complications. Perioperative levels of macrophage migration inhibitory factor (MIF) and other inflammatory mediators could be implicated in adverse outcomes in cardiac surgery.

Methods

Serum levels of MIF, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, IL-6 and IL-10 from 93 patients subjected to CPB were measured by enzyme-linked immunosorbent assay and compared with specific and global postoperative organ dysfunctions through multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA).

Results

Most of the cytokines measured had a peak of production between 3 and 6 hours after CPB, but maximum levels of MIF occurred earlier, at the cessation of CPB. Among specific organ dysfunctions, the most frequent was hematological, occurring in 82% of the patients. Circulatory impairment was observed in 73.1% of the patients, and 51% of these needed inotropics or vasopressors within the first 24 hours after surgery. The third most frequent dysfunction was pulmonary, occurring in 48.4% of the patients. Preoperative levels of MIF showed a relevant direct correlation with the intensity of global organ dysfunction measured by SOFA (ρ = 0.46, p < 0.001) and MODS (ρ = 0.50, p < 0.001) on the third day after surgery. MCP-1 production was associated with postoperative thrombocytopenia, and MIF was related to the use of a high dose of vasopressors in patients with cardiovascular impairment and also to lower values of the ratio of partial arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) registered in the first 24 hours after CPB.

Conclusion

Despite the multifactorial nature of specific or multiple organ dysfunctions, MIF should be explored as a predicting factor of organ dysfunction, or even as a potential therapeutic target in decreasing postoperative complications.
Appendix
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Literature
1.
go back to reference Butler J, Rocker GM, Westaby S: Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 1993, 55: 552-559.CrossRefPubMed Butler J, Rocker GM, Westaby S: Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 1993, 55: 552-559.CrossRefPubMed
2.
go back to reference Andersen LW, Baek L, Degn H, Lehd J, Krasnik M, Rasmussen JP: Presence of circulating endotoxin during cardiac operations. J Thorac Cardiovasc Surg. 1987, 93: 115-119.PubMed Andersen LW, Baek L, Degn H, Lehd J, Krasnik M, Rasmussen JP: Presence of circulating endotoxin during cardiac operations. J Thorac Cardiovasc Surg. 1987, 93: 115-119.PubMed
3.
go back to reference Ruel M, Bianchi C, Khan TA, Liddicoat JR, Voisine P, Araujo E, Lyon H, Kohane IS, Libermann TA, Selke FW: Gene expression after cardiopulmonary bypass and cardioplegic arrest. J Thorac Cardiovasc Surg. 2003, 126: 1521-1530. 10.1016/S0022-5223(03)00969-3.CrossRefPubMed Ruel M, Bianchi C, Khan TA, Liddicoat JR, Voisine P, Araujo E, Lyon H, Kohane IS, Libermann TA, Selke FW: Gene expression after cardiopulmonary bypass and cardioplegic arrest. J Thorac Cardiovasc Surg. 2003, 126: 1521-1530. 10.1016/S0022-5223(03)00969-3.CrossRefPubMed
4.
go back to reference Wan S, Leclerc JL, Vincent JL: Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. Ann Thorac Surg. 1997, 63: 269-276. 10.1016/S0003-4975(96)00931-9.CrossRefPubMed Wan S, Leclerc JL, Vincent JL: Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. Ann Thorac Surg. 1997, 63: 269-276. 10.1016/S0003-4975(96)00931-9.CrossRefPubMed
5.
go back to reference Gessler P, Pretre R, Hohl V, Rousson V, Fischer J, Dahinden C: CXC-chemokine stimulation of neutrophils correlates with plasma levels of myeloperoxidase and lactoferrin and contributes to clinical outcome after pediatric cardiac surgery. Shock. 2004, 22: 513-520. 10.1097/01.shk.0000145939.54838.51.CrossRefPubMed Gessler P, Pretre R, Hohl V, Rousson V, Fischer J, Dahinden C: CXC-chemokine stimulation of neutrophils correlates with plasma levels of myeloperoxidase and lactoferrin and contributes to clinical outcome after pediatric cardiac surgery. Shock. 2004, 22: 513-520. 10.1097/01.shk.0000145939.54838.51.CrossRefPubMed
6.
go back to reference Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 2003, 197: 1467-1476. 10.1084/jem.20030286.PubMedCentralCrossRefPubMed Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 2003, 197: 1467-1476. 10.1084/jem.20030286.PubMedCentralCrossRefPubMed
7.
go back to reference Leng L, Bucala R: Macrophage migration inhibitory factor. Crit Care Med. 2005, 33 (12 Suppl): S475-S477. 10.1097/01.CCM.0000191278.04636.D8.CrossRefPubMed Leng L, Bucala R: Macrophage migration inhibitory factor. Crit Care Med. 2005, 33 (12 Suppl): S475-S477. 10.1097/01.CCM.0000191278.04636.D8.CrossRefPubMed
8.
go back to reference Bucala R: MIF rediscovered: cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response. FASEB J. 1996, 10 (14): 1607-1613.PubMed Bucala R: MIF rediscovered: cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response. FASEB J. 1996, 10 (14): 1607-1613.PubMed
9.
go back to reference Gando S, Nishihira J, Kobayashi S, Morimoto Y, Nanzaki S, Kemmotsu O: Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med. 2001, 27: 1187-1193. 10.1007/s001340000818.CrossRefPubMed Gando S, Nishihira J, Kobayashi S, Morimoto Y, Nanzaki S, Kemmotsu O: Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome. Intensive Care Med. 2001, 27: 1187-1193. 10.1007/s001340000818.CrossRefPubMed
10.
go back to reference Calandra T, Roger T: Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003, 3: 791-800. 10.1038/nri1200.CrossRefPubMed Calandra T, Roger T: Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003, 3: 791-800. 10.1038/nri1200.CrossRefPubMed
11.
go back to reference Beishuizen A, Thijs LG, Haanen C, Vermes I: Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness. J Clin Endocrinol Metab. 2001, 86: 2811-2816. 10.1210/jc.86.6.2811.CrossRefPubMed Beishuizen A, Thijs LG, Haanen C, Vermes I: Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness. J Clin Endocrinol Metab. 2001, 86: 2811-2816. 10.1210/jc.86.6.2811.CrossRefPubMed
13.
go back to reference Roger T, David J, Glauser MP, Calandra T: MIF regulates innate immune response through modulation of Toll-like receptor 4. Nature. 2001, 414: 920-924. 10.1038/414920a.CrossRefPubMed Roger T, David J, Glauser MP, Calandra T: MIF regulates innate immune response through modulation of Toll-like receptor 4. Nature. 2001, 414: 920-924. 10.1038/414920a.CrossRefPubMed
14.
go back to reference de Mendonça-Filho HTF, Gomes RV, Campos LAA, Tura B, Nunes EM, Gomes R, Bozza F, Bozza PT, Castro-Faria-Neto HC: Circulating levels of macrophage migration inhibitory factor are associated to mild pulmonary dysfunction following cardiopulmonary bypass. Shock. 2004, 22: 533-537. 10.1097/01.shk.0000142817.84070.df.CrossRefPubMed de Mendonça-Filho HTF, Gomes RV, Campos LAA, Tura B, Nunes EM, Gomes R, Bozza F, Bozza PT, Castro-Faria-Neto HC: Circulating levels of macrophage migration inhibitory factor are associated to mild pulmonary dysfunction following cardiopulmonary bypass. Shock. 2004, 22: 533-537. 10.1097/01.shk.0000142817.84070.df.CrossRefPubMed
15.
go back to reference Luster AD: Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med. 1998, 338: 436-445. 10.1056/NEJM199802123380706.CrossRefPubMed Luster AD: Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med. 1998, 338: 436-445. 10.1056/NEJM199802123380706.CrossRefPubMed
16.
go back to reference Nannizzi-Alaimo L, Rubenstein MH, Alves VL, Leong GY, Phillips DR, Gold HK: Cardiopulmonary bypass induces release of soluble CD40 ligand. Circulation. 2002, 105: 2849-2854. 10.1161/01.CIR.0000019068.32280.B3.CrossRefPubMed Nannizzi-Alaimo L, Rubenstein MH, Alves VL, Leong GY, Phillips DR, Gold HK: Cardiopulmonary bypass induces release of soluble CD40 ligand. Circulation. 2002, 105: 2849-2854. 10.1161/01.CIR.0000019068.32280.B3.CrossRefPubMed
17.
go back to reference Wang H, Tracey KJ: Tumor necrosis factor, interleukin-6, macrophage migration inhibitory factor and macrophage inflammatory protein-1 in inflammation. Inflammation: Basic Principles and Clinical Correlates. Edited by: Gallin JI, Snyderman R. 1999, Philadelphia: Lippincott Willians & Wilkins, 471-486. 3 Wang H, Tracey KJ: Tumor necrosis factor, interleukin-6, macrophage migration inhibitory factor and macrophage inflammatory protein-1 in inflammation. Inflammation: Basic Principles and Clinical Correlates. Edited by: Gallin JI, Snyderman R. 1999, Philadelphia: Lippincott Willians & Wilkins, 471-486. 3
19.
go back to reference Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R: European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999, 16: 9-13. 10.1016/S1010-7940(99)00134-7.CrossRefPubMed Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R: European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999, 16: 9-13. 10.1016/S1010-7940(99)00134-7.CrossRefPubMed
20.
go back to reference Marshall JC, Cook D, Cristou NV, Sprung CL, Sibbald WJ: Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995, 23: 1638-1652. 10.1097/00003246-199510000-00007.CrossRefPubMed Marshall JC, Cook D, Cristou NV, Sprung CL, Sibbald WJ: Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995, 23: 1638-1652. 10.1097/00003246-199510000-00007.CrossRefPubMed
21.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sequential Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996, 22: 707-710.CrossRefPubMed Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sequential Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996, 22: 707-710.CrossRefPubMed
22.
go back to reference Bozza M, Satoskar AR, Lin G, Lu B, Humbles AA, Gerard C, David JR: Targeted disruption of migration inhibitory factor gene revels its critical role in sepsis. J Exp Med. 1999, 189: 341-346. 10.1084/jem.189.2.341.PubMedCentralCrossRefPubMed Bozza M, Satoskar AR, Lin G, Lu B, Humbles AA, Gerard C, David JR: Targeted disruption of migration inhibitory factor gene revels its critical role in sepsis. J Exp Med. 1999, 189: 341-346. 10.1084/jem.189.2.341.PubMedCentralCrossRefPubMed
23.
go back to reference Huang XR, Chunhui CW, Chen YX: Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats. Gastroenterology. 2001, 121: 619-630. 10.1053/gast.2001.27205.CrossRefPubMed Huang XR, Chunhui CW, Chen YX: Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats. Gastroenterology. 2001, 121: 619-630. 10.1053/gast.2001.27205.CrossRefPubMed
24.
go back to reference Chanon F, Metz CN, Bucala R, Lestur O: Endotoxin-induced myocardial dysfunction: effects of macrophage migration inhibitory factor neutralization. Circ Res. 2005, 96: 1095-1102. 10.1161/01.RES.0000168327.22888.4d.CrossRef Chanon F, Metz CN, Bucala R, Lestur O: Endotoxin-induced myocardial dysfunction: effects of macrophage migration inhibitory factor neutralization. Circ Res. 2005, 96: 1095-1102. 10.1161/01.RES.0000168327.22888.4d.CrossRef
25.
go back to reference Tanaka T, Kuroiwa T, Ikeuchi H, Ota F, Kaneko Y, Ueki K, Tsukada Y, Mcinnes IB, Boumpas DT, Nojima Y: Human platelets stimulate mesangial cells to produce monocyte chemoattractant protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury. J Am Soc Nephrol. 2002, 13: 2488-2496. 10.1097/01.ASN.0000029588.07166.20.CrossRefPubMed Tanaka T, Kuroiwa T, Ikeuchi H, Ota F, Kaneko Y, Ueki K, Tsukada Y, Mcinnes IB, Boumpas DT, Nojima Y: Human platelets stimulate mesangial cells to produce monocyte chemoattractant protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury. J Am Soc Nephrol. 2002, 13: 2488-2496. 10.1097/01.ASN.0000029588.07166.20.CrossRefPubMed
26.
go back to reference Schumacher K, Korr S, Vazques-Jimenez JF, von Bernuth G, Duchateau J, Seghaye M: Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?. Crit Care. 2005, 9: R549-R555. 10.1186/cc3794.PubMedCentralCrossRefPubMed Schumacher K, Korr S, Vazques-Jimenez JF, von Bernuth G, Duchateau J, Seghaye M: Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?. Crit Care. 2005, 9: R549-R555. 10.1186/cc3794.PubMedCentralCrossRefPubMed
27.
go back to reference Bocsi J, Hambsch J, Osmancik P, Schneider P, Valet G, Tárnok A: Preoperative prediction of pediatric patients with effusions and edema following cardiopulmonary bypass surgery by serological and routine laboratory data. Crit Care. 2002, 6: 226-233. 10.1186/cc1494.PubMedCentralCrossRefPubMed Bocsi J, Hambsch J, Osmancik P, Schneider P, Valet G, Tárnok A: Preoperative prediction of pediatric patients with effusions and edema following cardiopulmonary bypass surgery by serological and routine laboratory data. Crit Care. 2002, 6: 226-233. 10.1186/cc1494.PubMedCentralCrossRefPubMed
28.
go back to reference Leng L, Bucala R: Macrophage migration inhibitory factor. Crit Care Med. 2005, 33 (12 Suppl): S475-S477. 10.1097/01.CCM.0000191278.04636.D8.CrossRefPubMed Leng L, Bucala R: Macrophage migration inhibitory factor. Crit Care Med. 2005, 33 (12 Suppl): S475-S477. 10.1097/01.CCM.0000191278.04636.D8.CrossRefPubMed
Metadata
Title
Circulating inflammatory mediators and organ dysfunction after cardiovascular surgery with cardiopulmonary bypass: a prospective observational study
Authors
Hugo Tannus Furtado de Mendonça-Filho
Kelly Cristina Pereira
Mariane Fontes
Daniel Augusto de Souza Aranha Vieira
Maria Lucia A Furtado de Mendonça
Luiz Antonio de Almeida Campos
Hugo Caire Castro-Faria-Neto
Publication date
01-04-2006
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2006
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc4857

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