Decrease of Perforin Expressing Lymphocytes after On-Pump Coronary Artery Bypass Grafting Surgery Irrespective of Carbohydrate Preoperative Oral Feeding

  • Jadranko Sokolic Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
  • Danijel Knezevic Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
  • Janja Kuharic Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
  • Igor Medved Department of Surgery, Faculty of Medicine, University of Rijeka, Croatia
  • Alan Sustic Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
  • Zeljko Zupan Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
  • Gordana Laskarin Division of Cardiology, Hospital for Medical Rehabilitation of the Hearth and Lung Diseases and Rheumatism “Thalassotherapia-Opatija,” Opatija, Croatia
  • Tomislav Tadin Ultrasound Diagnostic Service, Health Centre Rijeka, Rijeka, Croatia
  • Vlatka Sotošek Tokmadžić Department of Anesthesia, Resuscitation, Emergency and Intensive Care Medicine, Faculty of Medicine, University of Rijeka, Croatia
Keywords: Cell immunity, Coronary artery bypass grafting surgery, Oral Feeding, Perforin


Background: Coronary artery bypass grafting (CABG) surgery continues to be the gold standard for treating the patients with coronary artery disease. CABG surgery can be performed on or off cardiopulmonary bypass, termed as on-pump or off-pump CABG, respectively. It has been shown that CABG surgery, preferably on-pump CABG surgery, leads to the changes of cell immunity during perioperative and early postoperative period. The mechanisms of regulation of the immune response in patients during and early after surgical revascularization are not fully understood.

The aim of this study was to investigate the influence of carbohydrate preoperative oral feeding on frequency and perforin expression in peripheral blood lymphocytes in patients after on- or off-pump CABG surgery in early postoperative period.

Patients and methods: In this prospective clinical study, 80 patients scheduled for CABG surgery were included in the study. The patients were randomly allocated into four groups (20 in each group): patients in Group 1 underwent on-pump CABG and did not receive carbohydrate preoperative oral feeding; patients in Group 2 underwent on-pump CABG and were preoperatively fed; patients in Group 3 underwent off-pump CABG and did not receive carbohydrate preoperative oral feeding; while patients in Group 4 underwent off-pump CABG and received carbohydrate preoperative oral feeding. Blood samples were collected immediately before (T1), 24 (T2) and 72 (T3) hours after the surgery. Peripheral blood mononuclear cells were isolated by gradient centrifugation and simultaneously labelled by antigens using fluorochrome-conjugated monoclonal antibodies. Frequency of T lymphocytes, NK and NKT cells, their subsets as well as their perforin expression were detected, and analyzed by flow cytometry.

Results: There was significant decrease in frequency of CD3+ and CD3+CD4+ cells, as well as perforin expressing CD3+CD8+ cells in patients who underwent on-pump CABG in comparison to patients who underwent off-pump CABG 24 hours after the surgery. Carbohydrate preoperative oral feeding did not effect changes in lymphocytes subpopulations and perforin expression at any time point.

Conclusion: Decreases of CD3+ cells on account of CD3+CD4+ subsets, and perforin expressing cells on account of CD3+CD8+ perforin+ cells were found in patients who had undergone on-pump CABG, but not in patients who had undergone off-pump CABG surgery, irrespectively of carbohydrate preoperative oral feeding.


Abbate A, Bussani R, Sinagra G, et al. 2008. Right ventricular cardiomyocyte apoptosis in patients with acute myocardial infarction of the left ventricular wall. Am J Cardiol 102:658-62. Akasaka Y, Morimoto N, Ishikawa Y, et al. 2006. Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction. Mod Pathol 19:588-98.

Akbas H, Erdal AC, Demiralp E, Alp M. 2002. Effects of coronary artery bypass grafting on cellular immunity with or without cardiopulmonary bypass: changes in lymphocytes subsets. Cardiovasc Surg 10:586-9.

Allavena P, Giardina G, Bianchi G, Mantovani A. 1997. IL-15 is chemotactic for natural killer cells and stimulates their adhesion to vascular endothelium. J Leukoc Biol 61:729-35.

Anastasilakis CD, Ioannidis O, Gkiomisi AI, Botsios D. 2013. Artificial nutrition and intestinal mucosal barrier functionality. Digestion 88:193-208.

Bujak M, Frangogiannis NG. 2009. The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp (Warsz) 57:165-76.

Buxton BF, Hayward PA. 2013. The art of arterial revascularization-total arterial revascularization in patients with triple vesselcoronary artery disease. Ann Cardiothorac Surg 2:543-51.

Calafiore AM, Di Mauro M, Canosa C, Di Giammarco G, Iaco AL. 2003. Contini M. Myocardial revascularization with and without cardiopulmonary bypass: advantages, disadvantages and similarities. Eur J Cardiothorac Surg 24:953-60.

Chávez-Galán L, Arenas-Del Angel MC, Zenteno E, Chávez R, Lascurain R. 2009. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol 6:15-25.

Finegold JA, Asaria P, Francis DP. 2012. Mortality from ischaemic heart disease by country, region and age: Statistics from World Health Organisation and United Nations. Int J Cardiol 168:934-45.

Jankovicová K, Kudlová MT, Kolácková M, et al. 2008. The effect of cardiac surgery on peripheral blood lymphocyte populations. Acta Medica (Hradec Kralove) 51:25-9.

Jeremias A, Kaul S, Rosengart TK, Gruberg L, Brown DL. 2009. The impact of revascularization on mortality in patients with nonacute coronary artery disease. Am J Med 122:152-61.

Kazmierski J, Banys A, Latek J, Bourke J, Jaszewski R. 2014. Raised IL-2 and TNF-α concentrations are associated with postoperative delirium in patients undergoing coronary-artery bypass graft surgery. Int Psychogeriatr 26:845-55.

Laskarin G, Zaputovic L, Persic V, Ruzic A, Sotosek Tokmadzic V. 2012. Harmful immune reactions during acute myocardial infarction. Med Hypotheses 78:703-6.

Ludwig RB, Paludo J, Fernandes D, Scherer F. 2013. Lesser time of preoperative fasting and early postoperative feeding are safe? Arq Bras Cir Di 26:54-8.

Martins TB, Anderson JL, Muhlestein JB, et al. 2006. Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay. Am J Clin Pathol 125:906-13.

Molfino A, Gioia G, Fanelli FR, Muscaritoli M. 2014. The role for dietary omega-3 fatty acids supplementation in older adults. Nutrients 6:4058-72.

Møller CH, Steinbrüchel DA. 2014. Off-pump versus on-pump coronary artery bypass grafting. Curr Cardiol Rep 16:455.

Orhan G, Sargin M, Senay S, et al. 2007. Systemic and myocardial inflammation in traditional and off pump cardiac surgery. Tex Heart Inst J 34:160-5.

Perera PY, Lichy JH, Waldmann TA, Perera LP. 2012. The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use. Microbes Infect 14:247-61.

Persic V, Ruzic A, Miletic B, et al. 2012. Granulysin expression in lymphocytes that populate the peripheral blood and the myocardium after an acute coronary event. Scand J Immunol 78:231-42.

Pipkin ME, Lieberman J. 2007. Delivering the kiss of death: progress on understanding how perforin works. Curr Opin Immunol 19:301-8.

Solomon MD, Tirupsur A, Hytopoulos E, et al. 2013. Clinical utility of a novel coronary heart disease risk-assessment test to further classify intermediate-risk patients. Clin Cardiol 36:621-7.

Subjective Global Assessment of Nutritional Status.

Takagi H, Watanabe T, Mizuno Y, Kawai N, Umemoto T; for the ALICE (All-Literature Investigation of Cardiovascular Evidence) Group. 2014. A meta-analysis of adjusted risk estimates for survival from observational studies of complete versus incomplete revascularization in patients with multivessel disease undergoing coronary artery bypass grafting. Interact Cardiovasc Thorac Surg 18:679-82.

Takayama T, Hiro T, Hirayama A. 2010. Is angioplasty able to become the gold standard of treatment beyond bypass surgery for patients with multivessel coronary artery disease? Therapeutic strategies for 3-vessel coronary artery disease: OPCAB vs PCI (PCI-Side). Circ J 74:2744-9.

Tokmadzic VS, Tsuji Y, Bogovic T, et al. 2002. IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes. Am J Reprod Immunol 48:191-200.

Windecker S, KolhP, Alfonso F, et al. 2014. 2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 34:2541-619.

Zal B, Kaski JC, Akiyu JP, et al. 2008. Differential pathways govern CD4+CD28- T cell proinflammatory and effector responses in patients with coronary artery disease. J Immunol 81:5233-41.

Zuidema MY, Zhang C. 2010. Ischemia/reperfusion injury: The role of immune cells. World J Cardiol 2:325-32.