The effect of Erythropoietin administration on the serum level of YKL-40, pro-BNP and IL-6 in coronary surgery patients

Document Type : Research article

Authors

1 Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Clinical Research and Development Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Background: Cardiopulmonary bypass and aortic clamping evokes the obligatory global myocardial ischemia and dysfunction with a significant inflammatory response. The discrepancy about cardioprotective effects of erythropoietin still exist. The aim of this study was to assess the clinical immunomodulatory effects of EPO on serum inflammatory biomarkers (YKL-40, IL-6 ) and cardiac biomarkers, (pro-BNP, CK-MB and troponin).
Methods: In this randomized double blind clinical trial, 132 patients admitted for elective coronary surgery with CPB were randomly assigned in one of three groups: 1- group EPO-A (n = 35) infusion of 300 IU/Kg EPO after anesthesia induction and before undergoing CPB; 2- group EPO-CPB (n = 31) the same intervention during CPB; 3- placebo group (n = 66) saline infusion in the same volume. Cardiac enzymes and serum biomarkers were measured at intervals.
Results: There was a sharp increase in serum YKL-40 with a 24 h delay after CPB in all groups without significant difference. The increase in serum IL-6 was significant in EPO-CPB group compared with both other groups (P=0.001 and P=0.001, respectively). Serum pro-BNP reached maximum level 24 hours after operation in all groups; in group A significantly less than others (p=0.008). CK-MB increased significantly in all groups (p<0.001), less prominently in CPB-A group (p=0.03).
Conclusion: EPO administration before induced ischemia may be cardioprotective in terms of cardiac biomarkers in patients undergoing CABG with CPB.

Graphical Abstract

The effect of Erythropoietin administration on the serum level of YKL-40, pro-BNP and IL-6 in coronary surgery patients

Keywords


(1) Aljure OD and Fabbro M, 2nd. Cardiopulmonary Bypass and Inflammation: The Hidden Enemy. J Cardiothorac. Vasc. Anesth. (2019) 33: 346-7.
(2) Heydarpour M, Ejiofor J, Gilfeather M, Stone G, Gorham J, Seidman CE, Seidman JG, Yammine M, Body SC, Aranki SF and Muehlschlegel JD. Molecular Genetics of Lidocaine-Containing
Cardioplegia in the Human Heart During Cardiac Surgery. Ann. Thorac. Surg. (2018) 106: 1379-87.
(3) Dabbagh A, Rajaei S, Bahadori Monfared A, Keramatinia AA and Omidi K. Cardiopulmonary Bypass, Inflammation and How to Defy it: Focus on Pharmacological Interventions. Iran. J. Pharm. Res. (2012) 11: 705-14.
(4) Warren OJ, Watret AL, de Wit KL, Alexiou C, Vincent C, Darzi AW and Athanasiou T. The inflammatory response to cardiopulmonary bypass: part 2--anti-inflammatory therapeutic strategies. J Cardiothorac. Vasc. Anesth. (2009) 23: 384-93.
(5) Warren OJ, Smith AJ, Alexiou C, Rogers PL, Jawad N, Vincent C, Darzi AW and Athanasiou T. The inflammatory response to cardiopulmonary bypass: part 1--mechanisms of pathogenesis. J. Cardiothorac. Vasc. Anesth. (2009) 23: 223-31.
(6) Dabbagh A, Bastanifar E, Foroughi M, Rajaei S and Keramatinia AA. The effect of intravenous magnesium sulfate on serum levels of N-terminal pro-brain natriuretic peptide (NT pro BNP) in elective CABG with cardiopulmonary bypass. J. Anesth. (2013) 27: 693-8.
(7) Aryana P, Rajaei S, Bagheri A, Karimi F and Dabbagh A. Acute Effect of Intravenous Administration of Magnesium Sulfate on Serum Levels of Interleukin-6 and Tumor Necrosis Factor-alpha in Patients Undergoing Elective Coronary Bypass Graft With Cardiopulmonary Bypass. Anesth. Pain Med. (2014) 4: e16316.
(8) Foroughi M, Rahimian H, Dabbagh A, Majidi M, Hekmat M, Beheshti M and Shahzamani M. Postoperative N-terminal pro-brain natriuretic peptide level in coronary artery bypass surgery with ventricular dysfunction after perioperative glucoseinsulin-potassium treatment. J. Cardiothorac. Vasc. Anesth. (2012) 26: 631-6.
(9) Sanchis-Gomar F, Garcia-Gimenez JL, ParejaGaleano H, Romagnoli M, Perez-Quilis C and Lippi G. Erythropoietin and the heart: physiological effects and the therapeutic perspective. Int. J. Cardiol. (2014) 171: 116-25.
(10) Talan MI, Ahmet I and Lakatta EG. Did clinical trials in which erythropoietin failed to reduce acute myocardial infarct size miss a narrow therapeutic window? PLoS One (2012) 7: e34819.
(11) Nairz M, Sonnweber T, Schroll A, Theurl I and Weiss G. The pleiotropic effects of erythropoietin in infection and inflammation. Microbes. Infect.
(2012) 14: 238-46.
(12) Wood MA, Goldman N, DePierri K, Somerville J
and Riggs JE. Erythropoietin increases macrophagemediated T cell suppression. Cell Immunol. (2016) 306-307: 17-24.
(13) Kastrup J. Can YKL-40 be a new inflammatory biomarker in cardiovascular disease? Immunobiology (2012) 217: 483-91.
(14) Kjaergaard AD, Johansen JS, Bojesen SE and Nordestgaard BG. Role of inflammatory marker YKL-40 in the diagnosis, prognosis and cause of cardiovascular and liver diseases. Crit. Rev. Clin. Lab Sci. (2016) 53: 396-408.
(15) Ganem F, Serrano CV, Jr., Fernandes JL, Blotta MH, Souza JA, Nicolau JC, Ramires JAF and Hueb WA Preoperative B-type natriuretic peptide, and not the inflammation status, predicts an adverse outcome for patients undergoing heart surgery. Interact Cardiovasc. Thorac. Surg. (2011) 12: 778-83.
(16) Jogia PM, Kalkoff M, Sleigh JW, Bertinelli A, La Pine M, Richards AM and Devlin G. NT-pro BNP secretion and clinical endpoints in cardiac surgery
intensive care patients. Anaesth. Intensive Care (2007) 35: 363-9.
(17) Litton E, Ho KM. The use of pre-operative brain natriuretic peptides as a predictor of adverse outcomes after cardiac surgery: a systematic review and meta-analysis. Eur. J. Cardiothorac. Surg.
(2012) 41: 525-34. (18) Fox AA, Shernan SK, Collard CD, Liu KY, Aranki SF, DeSantis SM, Jarolim P and Body SC. Preoperative B-type natriuretic peptide is as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting. J. Thorac. Cardiovasc. Surg (2008) 136: 452-61.
(19) Roubille F, Prunier F, Barrere-Lemaire S, Leclercq F, Piot C, Kritikou EA, Rhéaume E, Busseuil D and Tardif JC. What is the role of erythropoietin in acute myocardial infarct? Bridging the gap between experimental models and clinical trials. Cardiovasc. Drugs Ther. (2013) 27: 315-31.
(20) Prunier F, Biere L, Gilard M, Boschat J, Mouquet F, Bauchart JJ, Charbonnier B, Genée O, Guérin P, Warin-Fresse K, Durand E, Lafont A, Christiaens L, Abi-Khalil W, Delépine S, Benard T and Furber A. Single high-dose erythropoietin administration immediately after reperfusion in patients with STsegment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial. Am. Heart. J. (2012) 163: 200-7.e1.
(21) Payani N, Foroughi M and Dabbagh A. The Effect of Intravenous Administration of Active Recombinant Factor VII on Postoperative Bleeding in Cardiac Valve Reoperations; A Randomized Clinical Trial. Anesth Pain Med. (2015) 5: e22846.
(22) Arain F, Gullestad L, Nymo S, Kjekshus J, Cleland JG, Michelsen A, McMurray JJ, Wikstrand J, Aukrust P and Ueland T. Low YKL-40 in chronic heart failure may predict beneficial effects of statins: analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA). Biomarkers (2017) 22: 261-7.
(23) de Seigneux S, Ponte B, Weiss L, Pugin J, Romand JA, Martin PY and Saudan P. Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study. BMC Nephrol. (2012) 13: 132.
(24) Ferrario M, Arbustini E, Massa M, Rosti V, Marziliano N, Raineri C, Bertoletti A, De Ferrari GM, Klersy C, Angoli L, Bramucci E, Marinoni B, Ferlini M, Moretti E, Raisaro A, Repetto A, Schwartz PJ and Tavazzi L. High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study. Int. J. Cardiol. (2011) 147: 124-31.
(25) Harutyunyan M, Christiansen M, Johansen JS, Kober L, Torp-Petersen C and Kastrup J. The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure. Immunobiology (2012) 217: 652-6.
(26) Li J, Xu H, Gao Q and Wen Y. Effect of erythropoiesis-stimulating agents in acute STsegment elevation myocardial infarction: a systematic review. Eur. J. Clin. Pharmacol. (2012) 68: 469-77.
(27) Mocini D, Muso P, Guendouz E, De Marco L, Mele L, Cini R, Sordini P, Alois A, Costantino A, Arima S, Gentili C and Santini M. Endogenous erythropoietin and a single bolus of 40,000 IU
of epoetin alpha do not protect the heart from ischaemia-reperfusion injury during extracorporeal circulation for cardiac surgery. Perfusion (2008) 23: 187-92.
(28) Lin CH, Li HY, Jiang YD, Chang TJ and Chuang LM. Plasma YKL-40 predicts 10-year cardiovascular and all-cause mortality in individuals with type 2 diabetes. Clin. Endocrinol. (Oxf). (2013) 79: 185-91.
(29) Kastrup J, Johansen JS, Winkel P, Hansen JF, Hildebrandt P, Jensen GB, Jespersen CM, Kjøller E, Kolmos HJ, Lind I, Nielsen H and Gluud C, CLARICOR Trial Group. High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease. Eur. Heart. J. (2009) 30: 1066-72.
(30) Harutyunyan M, Gotze JP, Winkel P, Johansen JS, Hansen JF, Jensen GB, Hilden J, Kjøller E, Kolmos HJ, Gluud C and Kastrup J. Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: a prognostic study within the CLARICOR trial. Immunobiology (2013) 218: 945-51.
(31) Mygind ND, Iversen K, Kober L, Goetze JP, Nielsen H, Boesgaard S, M Bay, Johansen JS, Nielsen OW, Kirk V and Kastrup J. The inflammatory biomarker YKL-40 at admission is a strong predictor of overall mortality. J. Intern. Med. (2013) 273: 205-16.
(32) Nojgaard C, Host NB, Christensen IJ, Poulsen SH, Egstrup K, Price PA and Johansen JS. Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron. Artery Dis. (2008)19: 257-63.
(33) Harutyunyan M, Johansen JS, Mygind ND, Reuter SB and Kastrup J. Serum YKL-40 for monitoring myocardial ischemia after revascularization in patients with stable coronary artery disease. Biomark. Med. (2014) 8: 977-87.
(34) Wang Y, Ripa RS, Johansen JS, Gabrielsen A, Steinbrüchel DA, Friis T, Bindslev L, HaackSørensen M, Jørgensen E and Kastrup J. YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease. Scand. Cardiovasc. J. (2008) 42: 295-302.
(35) Poulsen TD, Andersen LW, Steinbruchel D, Gotze JP, Jorgensen OS and Olsen NV. Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery. J. Cardiothorac. Vasc. Anesth. (2009) 23: 316-23.
(36) Mastromarino V, Musumeci MB, Conti E, Tocci G and Volpe M. Erythropoietin in cardiac disease: effective or harmful? J. Cardiovasc. Med. (Hagerstown). (2013) 14: 870-8.
(37) Mastromarino V, Volpe M, Musumeci MB, Autore C and Conti E. Erythropoietin and the heart: facts and perspectives. Clin. Sci. (Lond). (2011) 120: 51-63.
(38) Koul D, Dhar S, Chen-Scarabelli C, Guglin M and Scarabelli TM. Erythropoietin: new horizon incardiovascular medicine. Recent Pat Cardiovasc Drug Discov. (2007) 2: 5-12.
(39) Majidi TehraniMM and ForoughiM. Erythropoietin in the clinical trials of the cardiac disease, what is and what is not. J. Cell Mol. Anesth. (2019) 4: 136- 44.
(40) Steppich B, Groha P, Ibrahim T, Schunkert H, Laugwitz KL, Hadamitzky M, Kastrati A, Ott I, Regeneration of Vital Myocardium in ST-Segment Elevation Myocardial Infarction by Erythropoietin (REVIVAL-3) Study Investigators. Effect of Erythropoietin in patients with acute myocardial infarction: five-year results of the REVIVAL-3 trial. BMC Cardiovasc Disord. (2017) 17: 38.
(41) Islamoglu F, Ozcan K, Apaydin AZ, Soydas C, Bayindir O and Durmaz I. Diagnostic accuracy of N-terminal pro-brain natriuretic peptide in the evaluation of postoperative left ventricular diastolic dysfunction. Tex. Heart Inst. J. (2008) 35: 111-8.
(42) Tasanarong A, Duangchana S, Sumransurp S, Homvises B and Satdhabudha O. Prophylaxis with erythropoietin versus placebo reduces acute kidney injury and neutrophil gelatinase associated lipocalin in patients undergoing cardiac surgery: a randomized, double-blind controlled trial. BMC. Nephrol. (2013) 14: 136.
(43) Tie HT, Luo MZ, Lin D, Zhang M, Wan JY and Wu QC. Erythropoietin administration for prevention of cardiac surgery-associated acute kidney injury: a meta-analysis of randomized controlled trials. Eur. J. Cardiothorac Surg. (2015) 48: 32-9.