Abstract
Introduction. Hyperlactatemia often occurs in patients after cardiac surgery with cardiopulmonary bypass, is a marker of the severity of the condition and a strong predictor of mortality. However, the development of hyperlactataemia does not always indicate oxygen deficiency, hypoperfusion, tissue hypoxia and the transition to "anaerobic glycolysis." After cardiac surgery, another type of lactate enhancement occurs on the background of satisfactory hemodynamics and adequate gas exchange, which is not associated with global hypoperfusion and tissue hypoxia, the mechanism for the development of which is not entirely clear. The formation of lactate is modulated by cytokines, such as TNF-α, IL-6, IL-8, IL-10, which are able to inhibit pyruvate dehydrogenase, increasing the level of lactate. A small pilot study was conducted, the purpose of which was to test the hypothesis whether the carrier of genetic variants of some inflammatory markers affects the development of hyperlactatemia after surgery for coronary artery bypass surgery. Material and methods. The study included 35 patients with coronary artery disease who underwent coronary artery bypass surgery. The analysis was carried out in two groups of patients: 1 group (5 patients) – in which the development of hyperlactatemia was observed in the postoperative period; group 2 (30 patients) – patients whose lactate levels were within normal values during surgery and in the postoperative period. Results. The analysis showed statistically significant differences between the two groups in the distribution of genotypes and alleles of two TNF gene polymorphisms (rs1800629 and rs1800796). Carrier associations of allele A and AG rs1800629 TNF genotype with the development of hyperlactataemia in the postoperative period have been identified, however, these associations did not reach statistical significance due to the small number of groups: allele A: odds ratio (OR) 7.25; 95% confidence interval (CI) 0.9–58,9; AG genotype: OR 9.33; 95% CI 0.94–92.4. Associations of a carrier of allele A and the AA rs1800796 TNF genotype with the development of hyperlactataemia in the postoperative period have been identified, however, these associations also did not reach statistical significance due to the small number of groups: allele A: OR 3.5; 95% CI 0.6–22.3; AA genotype: OR 20.3; 95% CI 0.71–578.0. Conclusion. A genetically determined increase in the levels of inflammatory cytokines, in particular TNF (rs1800629 and rs1800796), can lead to the development of hyperlactatemia after cardiovascular surgeries. The extreme complexity of the mechanisms of development of hyperlactatemia requires their deeper study and understanding. Keywords: hyperlactataemia; pyruvate dehydrogenase complex; aerobic and anaerobic glucose metabolism; genetic polymorphism of inflammatory mediators; tumor necrosis factor; interleukin-6; interleukin-10; systemic inflammatory response.
References
- Yaroustovsky M.B., Abramyan M.V., Krotenko N.P., Komardina E.V. Methods of molecular transfusion in the intensive therapy of critical states. Vestnik Rossiyskoy Akademii Meditsinskikh Nauk (Annals of the Russian Academy of Medical Sciences). 2016; 71 (4): 281–7 (in Russ.). DOI: 10.15690/vramn680
- Kushimoto S., Akaishi S., Sato T., Nomura R. Fujita M. et al. Lactate, a useful marker for disease mortality and severity but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients. Acute Med. Surg. 2016; 3: 293–7. DOI: 10.1002/ams2.207
- Solov’eva I.V. Lactate in assessing the severity of critical conditions. System approach for solving problems of clinical and diagnostic laboratories. Pushchino; 2018 (in Russ.).
- Samuilova D.Sh., Lobacheva G.V., Rakhimov A.A., Kolesnikova E.A., Samorodskaya I.V., Borovkova U.L. et al. Нyperlactatemia in patients cardiac surgery аnd its correlation with subsequent changes in laboratory parameters in the early postoperative period. Clinical Physiology of Blood Circulaiton. 2014; 3: 12–23 (in Russ.).
- Trekova N.A., Akselrod B.A., Yudichev I.I., Gus’kov D.A., Markin A.V., Popov A.M. Clinical aspects of the blood lactate dynamics during operations on the heart and the aorta in conditions of cardiopulmonary bypass. Anesteziologiya i Reanimatologiya (Russian Journal of Anaesthesiology and Reanimatology). 2016; 61 (5): 324–9 (in Russ.). DOI: /10.18821/0201-75632016-61-5-324-329
- Gillespie ĺ., Rosenstein P.G., Hughes D. Update: Clinical use of plasma lactate. Vet. Clin. North. Am. Small. Anim. Pract. 2017; 47 (2): 325–42. DOI: 10.1016/j.cvsm.2016.10.011
- Rosenstein P.G., Tennent-Brown B.S., Hughes D. Clinical use of plasma lactate concentration. Part 1: Physiology, pathophysiology, and measurement. J. Vet. Emerg. Crit. Care. (San Antonio). 2018; 28 (2): 85–105. DOI: 10.1111/vec.12708
- Rosenstein P.G., Tennent-Brown B.S., Hughes D. Clinical use of plasma lactate concentration. Part 2: Prognostic and diagnostic utility and the clinical management of hyperlactatemia. J. Vet. Emerg. Crit. Care. (San Antonio). 2018; 28 (2): 106–21. DOI: 10.1111/vec.12706
- Vary T.C., Martin L.F. Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis. Circ. Shock. 1993; 9 (4): 299–305.
- Jha M.K., Song G.J., Lee M.G., Jeoung N.H., Go Y., Harris R. A., Park D.H. et al. Metabolic connection of inflammatory pain: Pivotal role of a pyruvate dehydrogenase kinase-pyruvate dehydrogenase–lactic acid axis. J. Neurosc. 2015; 35 (42): 14353–69. DOI: 10.1523/JNEUROSCI.1910-15.2015
- Minton J., Sidebotham D.A. Hyperlactatemia and cardiac surgery. J. Extracorpor. Technol. 2017; 49: 7–15.
- Wilson A., Symons J., McDowell L., Duff G. Effects of a polymorphism in the human tumor necrosis factor promoter on transcriptional activation. PNAS. 1997; 94: 3195–9. DOI: 10.1073/pnas.94.7.3195
- Bittar M.N., John A.C., James B.B. et al. Tumor necrosis factor alpha influences the inflammatory response after coronary surgery. Ann. Thorac. Surg. 2006; 81: 132–8. DOI: 10.1016/j.athoracsur.2005.07.037
- Schroeder S., Borger N., Wrigge H. A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation. Ann. Thorac. Surg. 2003; 75: 534–7. DOI: 10.1016/S0003-4975(02)04377-1
- Boehem J., Hauner K., Grammer J. et al. Tumor necrosis factor-a-863C/A promoter polymorphism effects the inflammatory response after cardiac surgery. Eur. J. Cardiothorac. Surg. 2011; 40: 50–4. DOI: 10.1016/j.ejcts.2011.01.084
- Vary T.C., Hazen S.A., Maish G., Cooney R.N. TNF binding protein prevents hyperlactatemia and inactivation of PDH complex in skeletal muscle during sepsis. J. Surg. Res. 1998; 80 (1): 44–51. DOI: 10.1006/jsre.1998.5324
- Vary T.C., O'Neill P., Cooney R.N., Maish G., Shumate M. Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle. J. Parenter. Enteral. Nutr. 1999; 23 (4): 213–7. DOI: 10.1177/0148607199023004213
- Takubo K., Nagamatsu G., Kobayashi C.I, NakamuraIshizu A., Kobayashi H., Ikeda E. et al. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell. Stem. Cell. 2013; 12: 49–61. DOI: 10.1016/j.stem.2012. 10.011
- Wang Y., Huang Y., Yang J., Zhou Fang-Qiang, Zhao L., Zhou H. Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis. Military Med. Res. 2018; 5: 5–13. DOI: 10.1186/s40779-018-0160-y
About the authors
- Yuriy I. Buziashvili, Dr. Med. Sc., Professor, Academician of the Russian Academy of Sciences, Head of Department, orcid.org/0000-0001-7016-7541
- Inna V. Koksheneva, Dr. Med. Sc., Senior Researcher, orcid.org/0000-0002-8797-9340
- El’vina F. Tugeeva, Dr. Med. Sc., Senior Researcher, orcid.org/0000-0003-1751-4924
- Ol’ga M. Sherstyannikova, Cand. Med. Sc., Researcher, orcid.org/0000-0002-0340-695X
- Said T. Abukov, Cardiologist
- Evgeniy P. Golubev, Cand. Med. Sc., Researcher
