Abstract
The aim of this review is to analyze current understanding of the molecular mechanisms of altered sensitivity of the arterial baroreflex and peripheral chemoreflex and their potential association with perioperative complications.
Material and methods. The review includes an analysis of literature data presented in the PubMed database over the past 5 years and some earlier fundamental works.
Results. High risk of perioperative complications is associated with increased sensitivity of the peripheral chemoreflex and decreased sensitivity of the arterial baroreflex. The molecular mechanisms of such a relationship are unclear, but similar changes in reflex sensitivity are observed in chronic diseases of the cardiorespiratory system. Pathobiochemical factors capable of modeling the sensitivity of the chemoreflex and baroreflex include changes in the content of angiotensin II and 1-7, oxidative stress, decreased production of NO and other gasotransmitters, high concentrations of leptin, endothelin and proinflammatory cytokines, etc.
Conclusion. Connection of changes in the sensitivity of the peripheral chemoreflex and arterial baroreflex with a high risk of postoperative complications is associated with markers of cardiometabolic disorders in such patients. This is confirmed by the influence of the angiotensin-aldosterone system, hormones regulating carbohydrate and lipid metabolism, and gasotransmitters.
Keywords
Authors and affiliations
https://elibrary.ru/pfozes
K.A. Popov, I.M. Bykov, E.E. Esaulenko
Federal State Budgetary Institution of Higher Education “Kuban State Medical University” of the Ministry
of Health of the Russian Federation, M. Sedina str., 4, Krasnodar, 350063, Russian Federation
References
1. Заболотских И.Б., Трембач Н.В. Прогностическая роль чувствительности барорефлекса в оценке периоперационного риска. Вестник интенсивной терапии им. А.И. Салтанова. 2020; 2: 49–62. DOI: 10.21320/1818-474X-2020-2-49-62 [Zabolotskikh I.B., Trembach N.V. Predictive role of baroreflex sensitivity in the assessment of perioperative risk. Vestnik intensivnoi terapii im. A.I. Saltanova. 2020; 2: 49–62. DOI: 10.21320/1818-474X-2020-2-49-62 (in Russian)]
2. Trembach N., Zabolotskikh I. The pathophysiology of complications after laparoscopic colorectal surgery: Role of baroreflex and chemoreflex impairment. Pathophysiology. 2019; 26 (2): 115–20. DOI: 10.1016/j.pathophys.2019.05.004
3. Трембач Н.В., Федунец Д.Э., Дряев С.А., Мусаева Т.С., Вейлер Р.В., Трембач И.А., Заболотских И.Б. Влияние длительности произвольного порогового апноэ на течение анестезии при обширных абдоминальных операциях у пациентов с различным типом метаболизма: пилотное исследование. Современные проблемы науки и образования. 2023; 6: 101. DOI: 10.17513/spno.33083 [Trembach N.V., Fedunets D.E., Dryaev S.A., Musaeva T.S., Veyler R.V., Trembach I.A., Zabolotskikh I.B. Effect of duration of voluntary threshold apnea on the course of anesthesia during major abdominal surgery in patients with different metabolic types: a pilot study. Sovremennye problemy nauki i obrazovaniya. 2023; 6: 101. DOI: 10.17513/spno.33083 (in Russian)]
4. Lindsey B.G., Nuding S.C., Segers L.S., Morris K.F. Carotid bodies and the integrated cardiorespiratory response to hypoxia. Physiology (Bethesda). 2018; 33 (4): 281–97. DOI: 10.1152/physiol.00014.2018
5. Ogoh S., Tarumi T. Cerebral blood flow regulation and cognitive function: a role of arterial baroreflex function. J. Physiol. Sci. 2019; 69 (6): 813–23. DOI: 10.1007/s12576-019-00704-6
6. Kaufmann H., Norcliffe-Kaufmann L., Palma J.A. Baroreflex Dysfunction. N. Engl. J. Med. 2020; 382 (2): 163–78. DOI: 10.1056/NEJMra1509723
7. Conde S.V., Sacramento J.F., Melo B.F., Fonseca-Pinto R., Romero-Ortega M.I., Guarino M.P. Blood Pressure Regulation by the Carotid Sinus Nerve: Clinical Implications for Carotid Body Neuromodulation. Front Neurosci. 2022; 15: 725751. DOI: 10.3389/fnins.2021.725751
8. Kronsbein H., Gerlach D.A., Heusser K., Hoff A., Hoffmann F., Diedrich A., Ehmke H. еt al. Testing individual baroreflex responses to hypoxia-induced peripheral chemoreflex stimulation. Clin Auton Res. 2020; 30 (6): 531–40. DOI: 10.1007/s10286-019-00660-6
9. Brognara F., Castania J.A., Kanashiro A., Dias D.P.M., Salgado H.C. Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex. Front Immunol. 2021; 12: 637845. DOI: 10.3389/fimmu.2021.637845
10. Zera T., Moraes D.J.A., da Silva M.P., Fisher J.P., Paton J.F.R. The Logic of Carotid Body Connectivity to the Brain. Physiology (Bethesda). 2019; 34 (4): 264–82. DOI: 10.1152/physiol.00057.2018
11. Lazarov N.E., Atanasova D.Y. Carotid Body Dysfunction and Mechanisms of Disease. Adv Anat Embryol Cell Biol. 2023; 237: 123–38. DOI: 10.1007/978-3-031-44757-0_8
12. Conde S.V., Martins F.O., Sacramento J.F. Carotid body interoception in health and disease. Auton Neurosci. 2024; 255: 103207. DOI: 10.1016/j.autneu.2024.103207
13. Iturriaga R., Alcayaga J., Chapleau M., Somers V. Carotid body chemoreceptors: physiology, pathology, and implications for health and disease. Physiol Rev. 2021; 101: 1177–235. DOI:10.1152/physrev.00039.2019
14. Ortega-Sáenz P., López-Barneo J. Physiology of the carotid body: from molecules to disease. Annu Rev Physiol. 2020; 82: 127–49. DOI:10.1146/annurev-physiol-020518-114427
15. Zhang D., Liu J., Zheng H., Tu H., Muelleman R.L., Li Y.L. Effect of angiotensin II on voltage-gated sodium currents in aortic baroreceptor neurons and arterial baroreflex sensitivity in heart failure rats. J. Hypertens. 2015; 33 (7): 1401–10. DOI: 10.1097/HJH.0000000000000563
16. Pan Y.X., Gao L., Wang W.Z., Zheng H., Liu D., Patel K.P., Zucker I.H. еt al. Exercise training prevents arterial baroreflex dysfunction in rats treated with central angiotensin II. Hypertension. 2007; 49 (3): 519–27. DOI: 10.1161/01.HYP.0000256955.74461.93
17. Dos Santos Ferreira Silva M.P., Ferreira M.J., Shecaira T.P., da Silva Dias D., Kimura D.C., Irigoyen M.C., Gomes G.N. еt al. Impact of exercise training associated with enalapril treatment on blood pressure variability and renal dysfunctions in an experimental model of arterial hypertension and postmenopause. PLoS One. 2024; 19 (1): 0296687. DOI: 10.1371/journal.pone.0296687
18. Tran N., Garcia T., Aniqa M., Ali S., Ally A., Nauli S.M. Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States. Am J Biomed Sci Res. 2022; 15 (2): 153–77.
19. Légat L., Smolders I., Dupont A.G. AT1 Receptor Mediated Hypertensive Response to Ang II in the Nucleus Tractus Solitarii of Normotensive Rats Involves NO Dependent Local GABA Release. Front Pharmacol. 2019; 10: 460. DOI: 10.3389/fphar.2019.00460
20. Li B., Gao M.X., Yang W.L., Chai C., Zhang D.X., Cai H.Y., Liu J. еt al. Inhibitory effects of sulfur dioxide within the nucleus tractus solitarii of rats: involvement of Calcium Ion channels, Adenine nucleoside triphosphate-sensitive potassium channels, and the nitric oxide/cyclic Guanine trinucleotide phosphate pathway. Neuroreport. 2019; 30 (13): 914–20. DOI: 10.1097/WNR.0000000000001304
21. McMillan N.J., Jacob D.W., Shariffi B., Harper J.L., Foster G.E., Manrique-Acevedo C., Padilla J. еt al. Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults. Am. J. Physiol Heart Circ Physiol. 2024; 327 (1): H000. DOI: 10.1152/ajpheart.00253.2024
22. Keir D.A., Pogliaghi S., Inglis E.C., Murias J.M., Iannetta D. The Respiratory Compensation Point: Mechanisms and Relation to the Maximal Metabolic Steady State. Sports Med. 2024. DOI: 10.1007/s40279-024-02084-3
23. Tubek S., Niewiński P., Paleczny B., Langner A., Banasiak W., Ponikowski P. Human carotid bodies as a therapeutic target: new insights from a clinician’s perspective. Kardiol Pol. 2018; 76 (10): 1426–33. DOI: 10.5603/KP.a2018.0178
24. Tubek S., Niewinski P., Paleczny B., Langner-Hetmanczuk A., Banasiak W., Ponikowski P. Acute hyperoxia reveals tonic influence of peripheral chemoreceptors on systemic vascular resistance in heart failure patients. Sci Rep. 2021; 11 (1): 20823. DOI: 10.1038/s41598-021-99159-2
25. Torres-Torrelo H., Ortega-Sáenz P., Gao L., López-Barneo J. Lactate sensing mechanisms in arterial chemoreceptor cells. Nat Commun. 2021; 12: 4166. DOI:10.1038/s41467-021-24444-7
26. Shin M.K., Eraso C.C., Mu Y.P., Gu C., Yeung B.H.Y., Kim L.J., Liu X.R. еt al. Leptin Induces Hypertension Acting on Transient Receptor Potential Melastatin 7 Channel in the Carotid Body. Circ Res. 2019; 125 (11): 989–1002. DOI: 10.1161/CIRCRESAHA.119.315338
27. Iturriaga R., Del Rio R., Alcayaga J. Carotid Body Inflammation: Role in Hypoxia and in the Anti-inflammatory Reflex. Physiology (Bethesda). 2022; 37 (3): 128–40. DOI: 10.1152/physiol.00031.2021
28. Pauza A.G., Thakkar P., Tasic T., Felippe I., Bishop P., Greenwood M.P., Rysevaite-Kyguoliene K. еt al. GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition. Circ Res. 2022; 130 (5): 694–707. DOI: 10.1161/CIRCRESAHA.121.319874
29. Stocco E., Barbon S., Tortorella C., Macchi V., De Caro R., Porzionato A. Growth factors in the carotid body—an update. Int J Mol Sci. 2020; 21: 7267. DOI:10.3390/ijms21197267
30. Brognara F., Castania J.A., Kanashiro A., Dias D.P.M., Salgado H.C. Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex. Front Immunol. 2021; 12: 637845. DOI: 10.3389/fimmu.2021.637845
31. Liu X., He L., Stensaas L., Dinger B., Fidone S. Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. Am J Physiol Lung Cell Mol Physiol. 2009; 296 (2): 158–66. DOI: 10.1152/ajplung.90383.2008
32. Nouri-Vaskeh M., Sharifi A., Khalili N., Zand R., Sharifi A. Dyspneic and non-dyspneic (silent) hypoxemia in COVID-19: Possible neurological mechanism. Clin Neurol Neurosurg. 2020; 198: 106217. DOI: 10.1016/j.clineuro.2020.106217
33. Geraldes V., Carvalho M., Goncalves-Rosa N., Tavares C., Laranjo S., Rocha I. Lead toxicity promotes autonomic dysfunction with increased chemoreceptor sensitivity. Neurotoxicology. 2016; 54: 170–7. DOI: 10.1016/j.neuro.2016.04.016
34. Diaz-Jara E., Pereyra K., Vicencio S., Olesen M.A., Schwarz K.G., Toledo C., Diaz H.S. еt al. Superoxide dismutase 2 deficiency is associated with enhanced central chemoreception in mice: Implications for breathing regulation. Redox Biol. 2024; 69: 102992. DOI: 10.1016/j.redox.2023.102992
35. Bock J.M., Hanson B.E., Asama T.F., Feider A.J., Hanada S., Aldrich A.W., Dyken M.E. еt al. Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea. J. Appl Physiol (1985). 2021; 130 (1): 87–95. DOI: 10.1152/japplphysiol.00696.2020
36. Sutovska H., Babarikova K., Zeman M., Molcan L. Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review. Int. J. Mol. Sci. 2022; 23 (5): 2885. DOI: 10.3390/ijms23052885
37. Niewinski P., Engelman Z.J., Fudim M., Tubek S., Paleczny B., Jankowska E.A., Banasiak W. еt al. Clinical predictors and hemodynamic consequences of elevated peripheral chemosensitivity in optimally treated men with chronic systolic heart failure. J. Card Fail. 2013; 19 (6): 408–15. DOI: 10.1016/j.cardfail.2013.03.013
38. Langner-Hetmańczuk A., Tubek S., Niewiński P., Ponikowski P. The Role of Pharmacological Treatment in the Chemoreflex Modulation. Front Physiol. 2022; 13: 912616. DOI: 10.3389/fphys.2022.912616
39. Fontana M., Emdin M., Giannoni A., Iudice G., Baruah R., Passino C. Effect of acetazolamide on chemosensitivity, Cheyne-Stokes respiration, and response to effort in patients with heart failure. Am. J. Cardiol. 2011; 107 (11): 1675–80. DOI: 10.1016/j.amjcard.2011.01.060
40. Worley M.L., Reed E.L., Chapman C.L., Kueck P., Seymour L., Fitts T., Zazulak H. еt al. Acute beetroot juice consumption does not alter cerebral autoregulation or cardiovagal baroreflex sensitivity during lower-body negative pressure in healthy adults. Front Hum Neurosci. 2023; 17: 1115355. DOI: 10.3389/fnhum.2023.1115355
41. Giannoni A., Borrelli C., Gentile F., Mirizzi G., Coceani M., Paradossi U., Vergaro G. еt al. Central apnoeas and ticagrelor-related dyspnoea in patients with acute coronary syndrome. Eur. Heart J. Cardiovasc Pharmacother. 2021; 7 (3): 180–8. DOI: 10.1093/ehjcvp/pvaa089
42. Katayama P.L., Leirão I.P., Kanashiro A., Luiz J.P.M., Cunha F.Q., Navegantes L.C.C., Menani J.V. еt al. The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex. Brain Behav Immun. 2022; 102: 370–86. DOI: 10.1016/j.bbi.2022.03.014
43. Del Rio R., Moya E.A., Iturriaga R. Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link. Eur Respir J. 2010; 36 (1): 143–50. DOI: 10.1183/09031936.00158109