Abstract
Arterial hypocapnia (AH), induced by voluntary or forced hyperventilation of the lungs, is accompanied by a decrease in cerebral blood flow (due to an increase in the arteriole tone) and an increase in the affinity of hemoglobin for oxygen. As a result, an oxygen supply to cortical tissue decreases and zones with a critically low oxygen tension (pO2) are formed in brain tissue. The distribution of pO2 in cerebral cortex during AH has not been studied enough. The aim of the work was to evaluate the effectiveness of oxygen supply to brain tissue at the level of arterial and venous microvessels at AH. To do this, the following tasks were set: (1) to study the distribution of the pO2 on the arterial and venous microvessels of the rat cerebral cortex; (2) to analyze tissue pO2 profiles near the walls of these microvessels. On anesthetized Wistar rats under conditions of forced hyperventilation (PaCO2 = 17.1 ± 0.7 mm Hg), the distribution of oxygen tension on the wall of pial and radial arterioles with a lumen diameter of 7–70 µm and on the wall of pial and ascending venules with a lumen diameter of 7–300 µm was studied. In tissue, near the wall of cortical arterioles and venules with a lumen diameter of 10–20 µm, tissue pO2 profiles were measured. Measurements of pO2 during spontaneous breathing of the animal with air served as a control. All pO2 measurements were made using platinum polarographic microelectrodes with a tip diameter of 3–5 µm. Visualization of the electrode tip and microvessels was carried out using a LUMAM-K1 microscope with epiobjectives of the contact type. This work presents for the first-time direct measurements of pO2 on the walls of arterioles and venules of the rat cerebral cortex and in tissues at different distances from the walls of these microvessels at AH. It has been shown that AH results in significant decrease in the oxygen supply to cerebral cortex, that is manifested by a significant drop of the pO2’s on venous microvessels and in tissue in the immediate vicinity of the studied microvessels. It has been shown, that the role of arterioles as a direct source of oxygen to brain tissue, is significantly reduced during arterial hypocapnia. Forced hyperventilation results in significant deterioration of oxygen supply to cerebral cortex, despite elevated pO2 values in the systemic arterial blood and in blood of systemic cerebral veins (sagittal sinus).
REFERENCES
Curley G, Kavanagh BP, Laffey JG (2010) Hypocapnia and the injured brain: more harm than benefit. Crit Care Med 38(5): 1348–1359. https://doi.org/10.1097/CCM.0b013e3181d8cf2b
Tavel ME (2021) Hyperventilation Syndrome: Why Is It Regularly Overlooked? Am J Med 134(1): 13–15. https://doi.org/10.1016/j.amjmed.2020.07.006
Godoy DA, Rovegno M, Lazaridis C, Badenes R (2021) The effects of arterial CO2 on the injured brain: Two faces of the same coin. J Crit Care 61: 207–215. https://doi.org/10.1016/j.jcrc.2020.10.028
Kramer KEP, Anderson EE (2022) Hyperventilation-Induced Hypocapnia in an Aviator. Aerosp Med Hum Perform 93(5): 470–471. https://doi.org/10.3357/AMHP.5975.2022
Ringer SK, Clausen NG, Spielmann N, Weiss M (2019) Effects of moderate and severe hypocapnia on intracerebral perfusion and brain tissue oxygenation in piglets. Paediatr Anaesth 29(11): 1114–1121. https://doi.org/10.1111/pan.13736
Ito H, Kanno I, Ibaraki M, Hatazawa J, Miura S (2003) Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. J Cereb Blood Flow Metab 23(6): 665–670. https://doi.org/10.1097/01.WCB.0000067721.64998.F5
Harper AM, Glass HI (1965) Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. J Neurol Neurosurg Psychiatry 28(5): 449–452. https://doi.org/10.1136/jnnp.28.5.449
Nwaigwe CI, Roche MA, Grinberg O, Dunn JF (2000) Effect of hyperventilation on brain tissue oxygenation and cerebrovenous PO2 in rats. Brain Res 868(1): 150–156. https://doi.org/10.1016/s0006-8993(00)02321-0
Grote J, Zimmer K, Schubert R (1981) Effects of severe arterial hypocapnia on regional blood flow regulation, tissue PO2 and metabolism in the brain cortex of cats. Pflugers Arch 391(3): 195–199. https://doi.org/10.1007/BF00596170
Duling BR, Kuschinsky W, Wahl M (1979) Measurements of the perivascular PO2 in the vicinity of the pial vessels of the cat. Pflugers Arch 383(1): 29–34. https://doi.org/10.1007/BF00584471
Vovenko EP (1999) Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in normoxia: an experimental study on rats. Pflugers Arch 437(4): 617–623. https://doi.org/10.1007/s004240050825
Sharan M, Popel AS, Hudak ML, Koehler RC, Traystman RJ, Jones MD Jr (1998) An analysis of hypoxia in sheep brain using a mathematical model. Ann Biomed Eng 26(1): 48–59. https://doi.org/10.1114/1.50
Steyn-Ross DA, Steyn-Ross ML, Sleigh JW, Voss LJ (2023) Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick’s Law Model of Diffusion. Int J Mol Sci 24(7): 6450. https://doi.org/10.3390/ijms24076450
Sharan M, Vovenko EP, Vadapalli A, Popel AS, Pittman RN (2008) Experimental and theoretical studies of oxygen gradients in rat pial microvessels. J Cereb Blood Flow Metab 28(9): 1597–1604. https://doi.org/10.1038/jcbfm.2008.51
Lyons DG, Parpaleix A, Roche M, Charpak S (2016) Mapping oxygen concentration in the awake mouse brain. Elife 5: e12024. https://doi.org/10.7554/eLife.12024
Li B, Esipova TV, Sencan I, Kilic K, Fu B, Desjardins M, Moeini M, Kura S, Yaseen MA, Lesage F, Ostergaard L, Devor A, Boas DA, Vinogradov SA, Sakadzic S (2019) More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction. Elife 8: e42299. https://doi.org/10.7554/eLife.42299
Shih AY, Driscoll JD, Drew PJ, Nishimura N, Schaffer CB, Kleinfeld D (2012) Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. J Cereb Blood Flow Metab 32(7): 1277–1309. https://doi.org/10.1038/jcbfm.2011.196
Sakadzic S, Mandeville ET, Gagnon L, Musacchia JJ, Yaseen MA, Yucel MA, Lefebvre J, Lesage F, Dale AM, Eikermann-Haerter K, Ayata C, Srinivasan VJ, Lo EH, Devor A, Boas DA (2014) Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 5: 5734. https://doi.org/10.1038/ncomms6734
Parpaleix A, Goulam HY, Charpak S (2013) Imaging local neuronal activity by monitoring PO2 transients in capillaries. Nat Med 19(2): 241–246. https://doi.org/10.1038/nm.3059
Vovenko EP, Chuikin AE (2008) Oxygen tension in rat cerebral cortex microvessels in acute anemia. Neurosci Behav Physiol 38(5): 493–500. https://doi.org/10.1007/s11055-008-9007-4
Shonat RD, Johnson PC (1997) Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study. Am J Physiol 272(5 Pt 2): H2233–H2240. https://doi.org/10.1152/ajpheart.1997.272.5.H2233
Celaya-Alcala JT, Lee GV, Smith AF, Li B, Sakadzic S, Boas DA, Secomb TW (2021) Simulation of oxygen transport and estimation of tissue perfusion in extensive microvascular networks: Application to cerebral cortex. J Cereb Blood Flow Metab 41(3): 656–669. https://doi.org/10.1177/0271678X20927100
Ward J (2006) Oxygen delivery and demand. Surgery (Oxf) 24(10): 354–360. https://doi.org/10.1053/j.mpsur.2006.08.010
Sakadzic S, Yaseen MA, Jaswal R, Roussakis E, Dale AM, Buxton RB, Vinogradov SA, Boas DA, Devor A (2016) Two-photon microscopy measurement of cerebral metabolic rate of oxygen using periarteriolar oxygen concentration gradients. Neurophotonics 3 (4): 045005. https://doi.org/10.1117/1.NPh.3.4.045005
Nishimura N, Schaffer CB, Friedman B, Lyden PD, Kleinfeld D (2007) Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci USA 104(1): 365–370. https://doi.org/10.1073/pnas.0609551104
Kasischke KA, Lambert EM, Panepento B, Sun A, Gelbard HA, Burgess RW, Foster TH, Nedergaard M (2011) Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions. J Cereb Blood Flow Metab 31(1): 68–81. https://doi.org/10.1038/jcbfm.2010.158
Scheufler KM, Lehnert A, Rohrborn HJ, Nadstawek J, Thees C (2004) Individual value of brain tissue oxygen pressure, microvascular oxygen saturation, cytochrome redox level, and energy metabolites in detecting critically reduced cerebral energy state during acute changes in global cerebral perfusion. J Neurosurg Anesthesiol 16(3): 210–219. https://doi.org/10.1097/00008506-200407000-00005
Zhang K, Zhu L, Fan M (2011) Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases. Front Mol Neurosci 4: 5. https://doi.org/10.3389/fnmol.2011.00005
Vovenko EP, Chuikin AE (2010) Tissue oxygen tension profiles close to brain arterioles and venules in the rat cerebral cortex during the development of acute anemia. Neurosci Behav Physiol 40(7): 723–731. https://doi.org/10.1007/s11055-010-9318-0
West JB (2019) Three classical papers in respiratory physiology by Christian Bohr (1855–1911) whose work is frequently cited but seldom read. Am J Physiol Lung Cell Mol Physiol 316(4): L585–L588. https://doi.org/10.1152/ajplung.00527.2018
Vovenko EP, Chuikin AE (2013) Longitudinal Oxygen Tension Gradients in Small Cortical Microvessels in the Rat Brain on Development of Acute Anemia. Neurosci Behav Physiol 43(6): 748–754. https://doi.org/10.1007/s11055-013-9804-2
Funding
This work was supported by State Program 47 of the State Program “Scientific and Technological Development of the Russian Federation” (2019-2030), topic 0134-2019-0001.
Author information
Authors and Affiliations
Contributions
The idea of the work, conducting experiments, writing and editing the article—E.P.V. Conducting experiments, processing data, discussing the work, preparing a draft of the article—I.B.S.
Corresponding author
Ethics declarations
COMPLIANCE WITH ETHICAL STANDARDS
The studies were conducted in accordance with the regulations established by the MHSD of the Russian Federation no. 708n of 23.08.10 (“Rules of Laboratory Practice”), Directive 2010/63/EU of the European Parliament and Council of the European Union on the protection of animals used for scientific purposes, and the requirements of the Commission for the Control of the Keeping and Use of Laboratory Animals at the Institute of Physiology named after I.P. Pavlov, Russian Academy of Sciences (protocol no. 09/05 of 05.09.2022). I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences (Minutes no. 09/05 of 05.09.2022).
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.
Additional information
Translated by A. Dyomina
Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 8, pp. 1068–1079https://doi.org/10.31857/S0869813923080113.
Rights and permissions
About this article
Cite this article
Vovenko, E.P., Sokolova, I.B. Distribution of Oxygen Tension on Microvessels and in Tissue of Rat Brain Cortex at Severe Arterial Hypocapnia. J Evol Biochem Phys 59, 1392–1401 (2023). https://doi.org/10.1134/S0022093023040300
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0022093023040300