Brain tissue oxygen tension: Is it a derivative of arterial blood?,Critical Care

当前位置： X-MOL 学术 › Crit. Care › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Brain tissue oxygen tension: Is it a derivative of arterial blood?
Critical Care ( IF 15.1 ) Pub Date : 2022-09-23 , DOI: 10.1186/s13054-022-04130-w
Gurgen Harutyunyan ₁ , Varsenik Harutyunyan Jaghatspanyan ₂ , Emma Martirosyan ₃ , Rosa Isabel Benitez Bermejo ₄ , Garnik Harutyunyan ₂ , Andrés Sánchez Gimeno ₁ , Pau Ignasi García Zapata ₁ , Armen Varosyan ₅ , Suren Soghomonyan ₆

Affiliation

The article of Thomas Gargadennec’s et al. “Detection of cerebral hypoperfusion with a dynamic hyperoxia test using brain oxygenation pressure monitoring” [1] is a big step forward towards a new paradigm in neurotrauma: the high brain tissue oxygen pressure (PbrO₂) presence by oxygen challenge (OC) from baseline to 100% in brain-injured patients is in fact independent from local perfusion sufficiency (i.e. the cut-off of regional cerebral blood flow < 3.5 ml/100 gxmin). Accordingly, with OC the PbrO₂ in the tissue of traumatic brain injury (TBI) patients without hypoperfusion reaches up to 123 [96–138] mmHg (supplement 2) [1].

This daily challenge of PbrO₂, whose mechanisms of action in the end capillaries remain uncertain until today, is explained by authors as an “increase in interstitial oxygen diffusion at the arterial capillary side” [1].

Indeed, with OC in all groups of traumatic and non-traumatic brain injury patients, the PbrO₂ reaches to arterial oxygen pressure (PO₂) levels (i.e. 62 mmHg in hypoperfusion zones and 91 mmHg in no brain hypoperfusion zones). Therefore, the blood that is in said environment has to be arterial.

On the other hand, as confirmed by Johnston and colleagues, “normally it is assumed that there is a minimal oxygen gradient between the extracellular space and the end-capillary compartment, and thus that PbrO₂ reflects end-capillary oxygen tension” [2].

As we know, the Clark electrode measures PO₂ in a volume of 1 mm³, where there are millions of cells and hundreds of capillaries; this “small” volume encloses such a “megacontent” which is practically in an environment of the same pressure. Consequently, the end-capillary PO₂ in this volume is at least equal or higher than the PO₂ measured by PbrO₂ electrode.

Accepting data presented in the article that the changes of PbrO₂ by OC in all brain-injured patients raise to arterial levels of PO₂, we can confirm that in a fairly large homogeneous brain volume, the venous capillary side blood has arterial level of PO₂ by hyperoxia. As confirmation, the MRI-derived brain extracellular PO₂ data with OC (which includes a much larger volume of tissue) are consistent with data from the literature obtained using invasive techniques and exceed 100 mmHg [3].

However, current literature indicates no significant change in cerebral metabolic rate of brain tissue oxygen consumption by normobaric hyperoxia [4,5,6,7] and oxygen extraction fraction (OEF) at 0.56 ± 0.06 in reversible tissues [8]. That is, the OC at the end of cerebral capillaries causes high PO₂ which is typical to arterial blood with the presence of blood with low oxygen saturation of Hb (SO₂) (i.e. venous blood).

With the classical knowledge, it is impossible to explain the presence of such a high PO₂ at the end-capillary side of brain tissue: according to the sigmoid “S”-shaped oxyhaemoglobin dissociation curve (ODC), the SO₂ with OC in the brain tissue end-capillary part is expected to be near 100%, which would mean the miserly oxygen extraction and massive mitochondrial dysfunction by hyperoxia.

The solution of this puzzle is in the field of biochemistry: the described high increase in PbrO₂ with OC is possible only with intracapillary conformational change of haemoglobin (Hb) quaternary state from relaxed (R) to tens (T), which has a lower Hb–O₂ affinity, highest buffering capacity and hyperbolic and low form of ODC [9].

The existence of Hb T state in the cerebral microcirculation is essential: first, it increases PO₂ with low SO₂ in the capillary venous part. Second, it favours to equally distribute PO₂ among all cells by capillary length in homogeneous tissue. And finally, it incomparably increases Hb buffering capacity to maximum, reaching the human Haldane coefficient at 0.6 (i.e. the release of 1 mol of oxygen will allow the Hb to bind a 0.6 mol of H +) [9].

Assuming this, we can confirm that the increase in PbrO₂ by OC is a phenomenon due to T state of Hb in the cerebral venous capillary side with or without local perfusion involvement. Furthermore, the biological sense of cerebral autoregulation is to maintain Hb T quaternary state in the cerebral end-capillary part.

Acknowledgements are due to the authors who confirm the presence of arterial PO₂ equivalent PbrO₂ with OC in various types of brain injury patients, regardless of the state of local perfusion.

Thanks to this practical discovery and the biochemical explanation of the process (i.e. intracapillary R to T transition of Hb), many discrepancies in neurotrauma patients can be clarified (we have discussed in detail elsewhere) [10, 11].

Brain tissue oxygen pressure is derived from end-capillary oxygen tension independent of oxygen challenge and reflects the T state of haemoglobin.

Not applicable.

Gargadennec T, Ferraro G, Chapusette R, et al. Detection of cerebral hypoperfusion with a dynamic hyperoxia test using brain oxygenation pressure monitoring. Crit Care. 2022;26:35. https://doi.org/10.1186/s13054-022-03918-0.
Article PubMed PubMed Central Google Scholar
Johnston AJ, Steiner LA, Gupta AK, Menon DK. Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity. Br J Anaesth. 2003;90(6):774–86. https://doi.org/10.1093/bja/aeg104.
CAS Article PubMed Google Scholar
Muir ER, Cardenas DP, Duong TQ. MRI of brain tissue oxygen tension under hyperbaric conditions. Neuroimage. 2016;133:498–503. https://doi.org/10.1016/j.neuroimage.2016.03.040.
Article PubMed Google Scholar
Magnoni S, Ghisoni L, Locatelli M, Caimi M, Colombo A, Valeriani V, et al. Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a micro-dialysis study. J Neurosurg. 2003;98:952–8. https://doi.org/10.3171/jns.2003.98.5.0952.
Article PubMed Google Scholar
Diringer MN. Hyperoxia: Good or bad for the injured brain? Curr Opin Crit Care. 2008;14:167–71. https://doi.org/10.1097/MCC.0b013e3282f57552.
Article PubMed PubMed Central Google Scholar
Diringer MN, Aiyagari V, Zazulia AR, Videen TO, Powers WJ. Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron emission tomography in patients with acute severe head injury. J Neurosurg. 2007;106:526–9. https://doi.org/10.3171/jns.2007.106.4.526.
Article PubMed Google Scholar
Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation and oxidative metabolism. J Cereb Blood Flow Metab. 2012;32:1909–18. https://doi.org/10.1038/jcbfm.2012.93.
CAS Article PubMed PubMed Central Google Scholar
Powers WJ, Grubb RL Jr, Darriet D, Raichle ME. Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans. J Cereb Blood Flow Metab. 1985;5:600–8. https://doi.org/10.1038/jcbfm.1985.89.
CAS Article PubMed Google Scholar
Voet D, Voet JG. Biochemistry. 4th ed. New York: Wiley; 2010.
Google Scholar
Harutyunyan G, Harutyunyan G, Mkhoyan G. New viewpoint in exaggerated increase of PtiO2 with normobaric hyperoxygenation and reasons to limit oxygen use in neurotrauma patients. Front Med. 2018;5:119. https://doi.org/10.3389/fmed.2018.00119.
Article Google Scholar
Harutyunyan G, Avitsian R. Revisiting ischemia after brain injury: oxygen may not be the only problem. J Neurosurg Anesthesiol. 2020;32(1):5–8. https://doi.org/10.1097/ANA.0000000000000650.
Article PubMed Google Scholar

Download references

None to declare.

None.

Authors and Affiliations

Emergency Department, Hospital 9 de Octubre, VITHAS, Valle de la Ballestera 59, 46015, Valencia, Spain
Gurgen Harutyunyan, Andrés Sánchez Gimeno & Pau Ignasi García Zapata
Faculty of Pharmacy, Universitat De València, C. del Cementerio, 1, 46100, Burjassot, Valencia, Spain
Varsenik Harutyunyan Jaghatspanyan & Garnik Harutyunyan
Faculty of General Medicine, Yerevan State Medical University, 2 Koryun St, 0025, Yerevan, Armenia
Emma Martirosyan
Consorcio Hospital General Universitario de Valencia, Av. de les Tres Creus, 2, 46014, Valencia, Spain
Rosa Isabel Benitez Bermejo
Erebouni Medical Center, Titogradyan St. 14, 0087, Yerevan, Armenia
Armen Varosyan
Clinical Department of Anesthesiology, The Ohio State University Wexner Medical Center, N411 Doan Hall, 410 West 10th Avenue, Columbus, OH, 43210, USA
Suren Soghomonyan

Authors

Gurgen HarutyunyanView author publications
You can also search for this author in PubMed Google Scholar
Varsenik Harutyunyan JaghatspanyanView author publications
You can also search for this author in PubMed Google Scholar
Emma MartirosyanView author publications
You can also search for this author in PubMed Google Scholar
Rosa Isabel Benitez BermejoView author publications
You can also search for this author in PubMed Google Scholar
Garnik HarutyunyanView author publications
You can also search for this author in PubMed Google Scholar
Andrés Sánchez GimenoView author publications
You can also search for this author in PubMed Google Scholar
Pau Ignasi García ZapataView author publications
You can also search for this author in PubMed Google Scholar
Armen VarosyanView author publications
You can also search for this author in PubMed Google Scholar
Suren SoghomonyanView author publications
You can also search for this author in PubMed Google Scholar

Contributions

GH, VHJ, ASG and PIGZ wrote the manuscript; SS, GH, EM, AV and RIBB critically revised the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Gurgen Harutyunyan.

Ethics approval and consent to participate

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

Cite this article

Harutyunyan, G., Harutyunyan Jaghatspanyan, V., Martirosyan, E. et al. Brain tissue oxygen tension: Is it a derivative of arterial blood?. Crit Care 26, 286 (2022). https://doi.org/10.1186/s13054-022-04130-w

Download citation

Received: 19 May 2022
Accepted: 20 August 2022
Published: 23 September 2022
DOI: https://doi.org/10.1186/s13054-022-04130-w

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

中文翻译：

脑组织氧张力：它是动脉血的衍生物吗？

Thomas Gargadennec 等人的文章。“使用脑氧合压力监测通过动态高氧测试检测脑灌注不足”[1] 是朝着神经创伤新范式迈出的一大步：从基线开始氧挑战 (OC)导致的高脑组织氧压 (PbrO ₂ )脑损伤患者的 100% 实际上与局部灌注充足无关（即局部脑血流量的截止值 < 3.5 ml/100 gxmin）。因此，使用 OC 时，没有低灌注的创伤性脑损伤 (TBI) 患者组织中的 PbrO ₂高达 123 [96–138] mmHg（补充 2）[1]。

PbrO ₂的这一日常挑战，其在毛细血管末端的作用机制直到今天仍然不确定，作者将其解释为“动脉毛细血管侧的间质氧扩散增加”[1]。

事实上，在所有创伤性和非创伤性脑损伤患者组中使用 OC，PbrO ₂达到动脉氧压 (PO ₂ ) 水平（即在低灌注区为 62 mmHg，在无脑低灌注区为 91 mmHg）。因此，在所述环境中的血液必须是动脉的。

另一方面，正如 Johnston 及其同事所证实的，“通常假设细胞外空间和毛细血管末端隔室之间存在最小的氧梯度，因此 PbrO ₂反映了毛细血管末端氧张力”[2] .

众所周知，克拉克电极测量体积为 1 mm ^{3的 PO}₂，其中有数百万个细胞和数百个毛细血管；这个“小”的体积包含了这样一个“大容量”，实际上处于相同压力的环境中。因此，该体积中的末端毛细管PO ₂至少等于或高于PbrO ₂电极测得的PO _{2 。}

接受文章中提供的数据，即所有脑损伤患者的 OC对 PbrO _{2的变化升高到动脉水平的 PO}₂，我们可以确认在相当大的均匀脑容量中，静脉毛细血管侧血液具有动脉水平的 PO ₂高氧。作为确认，MRI 衍生的 OC 脑细胞外 PO ₂数据（包括更大体积的组织）与使用侵入性技术获得的文献数据一致，超过 100 mmHg [3]。

然而，目前的文献表明，常压高氧 [4,5,6,7] 和可逆组织中的氧提取分数 (OEF) 为 0.56 ± 0.06 [8] 对脑组织耗氧量的脑代谢率没有显着变化。也就是说，脑毛细血管末端的 OC 会导致高 PO ₂，这对于动脉血来说是典型的，同时存在 Hb (SO ₂ ) 低氧饱和度的血液（即静脉血）。

用经典知识无法解释脑组织毛细血管端侧存在如此高的 PO ₂：根据乙状结肠“S”形氧合血红蛋白解离曲线（ODC），SO ₂与 OC 在预计脑组织毛细血管末端部分接近100%，这意味着高氧导致的氧气提取和大量线粒体功能障碍。

这个难题的解决方案是在生物化学领域：所描述的 PbrO ₂与 OC 的高增加只有在血红蛋白 (Hb) 四元态从松弛 (R) 到数十 (T) 的毛细血管内构象变化时才有可能，其具有较低的Hb–O ₂亲和力、最高缓冲能力以及双曲线和低形式的 ODC [9]。

脑微循环中Hb T状态的存在是必不可少的：首先，它增加了毛细血管静脉部分低SO _2的PO_{2 。}其次，它倾向于通过均匀组织中的毛细血管长度将PO ₂均匀地分布在所有细胞中。最后，它无可比拟地将 Hb 缓冲能力提高到最大，达到人类 Haldane 系数为 0.6（即释放 1 mol 氧气将使 Hb 与 0.6 mol H + 结合）[9]。

假设这一点，我们可以确认OC增加的PbrO ₂是由于脑静脉毛细血管侧Hb的T状态引起的现象，有或没有局部灌注受累。此外，脑自动调节的生物学意义是维持脑毛细血管末梢部分的Hb T四元状态。

致谢是由于作者证实在各种类型的脑损伤患者中存在动脉 PO ₂等效 PbrO _{2和 OC，无论局部灌注状态如何。}

由于这一实际发现和过程的生化解释（即 Hb 的毛细血管内 R 到 T 转变），神经外伤患者的许多差异可以得到澄清（我们已在别处详细讨论）[10, 11]。

脑组织氧压来自与氧刺激无关的毛细血管末端氧张力，反映了血红蛋白的 T 状态。

不适用。

Gargadennec T、费拉罗 G、Chapusette R 等。使用脑氧合压力监测通过动态高氧测试检测脑灌注不足。暴击护理。2022；26:35。https://doi.org/10.1186/s13054-022-03918-0。
文章 PubMed PubMed Central Google Scholar
约翰斯顿 AJ、施泰纳 LA、古普塔 AK、梅农 DK。脑氧血管反应性和脑组织氧反应性。Br J Anaesth。2003；90(6):774–86。https://doi.org/10.1093/bja/aeg104。
CAS 文章 PubMed 谷歌学术
Muir ER，Cardenas DP，Duong TQ。高压条件下脑组织氧张力的MRI。神经影像。2016；133:498–503。https://doi.org/10.1016/j.neuroimage.2016.03.040。
文章 PubMed 谷歌学术
Magnoni S、Ghisoni L、Locatelli M、Caimi M、Colombo A、Valeriani V 等。严重颅脑损伤高氧后脑代谢缺乏改善：微透析研究。神经外科杂志。2003；98:952–8。https://doi.org/10.3171/jns.2003.98.5.0952。
文章 PubMed 谷歌学术
迪林格 MN。高氧：对受伤的大脑是好是坏？Curr Opin Crit Care。2008；14：167–71。https://doi.org/10.1097/MCC.0b013e3282f57552。
文章 PubMed PubMed Central Google Scholar
Diringer MN、Aiyagari V、Zazulia AR、Videen TO、Powers WJ。高氧对急性严重颅脑损伤患者使用正电子发射断层扫描测量的氧的脑代谢率的影响。神经外科杂志。2007；106:526-9。https://doi.org/10.3171/jns.2007.106.4.526。
文章 PubMed 谷歌学术
Xu F, Liu P, Pascual JM, Xiao G, Lu H. 缺氧和高氧对脑血流、血氧合和氧化代谢的影响。J Cereb 血流代谢。2012；32：1909-18。https://doi.org/10.1038/jcbfm.2012.93。
CAS 文章 PubMed PubMed Central Google Scholar
Powers WJ、Grubb RL Jr、Darriet D、Raichle ME。脑血流量和脑氧代谢率对人类脑功能和活力的需求。J Cereb 血流代谢。1985；5：600–8。https://doi.org/10.1038/jcbfm.1985.89。
CAS 文章 PubMed 谷歌学术
Voet D，Voet JG。生物化学。第 4 版。纽约：威利；2010 年。
谷歌学术
Harutyunyan G、Harutyunyan G、Mkhoyan G. 常压高氧合导致 PtiO2 过度增加的新观点以及限制神经外伤患者氧气使用的原因。前医学。2018；5:119。https://doi.org/10.3389/fmed.2018.00119。
文章谷歌学术
Harutyunyan G, Avitsian R. 重新审视脑损伤后的缺血：氧气可能不是唯一的问题。J Neurosurg 麻醉剂。2020；32（1）：5-8。https://doi.org/10.1097/ANA.0000000000000650。
文章 PubMed 谷歌学术

下载参考资料

无需申报。

没有任何。

作者和附属机构

急诊科，医院 9 de Octubre, VITHAS, Valle de la Ballestera 59, 46015, Valencia, Spain
Gurgen Harutyunyan、Andrés Sánchez Gimeno 和 Pau Ignasi García Zapata
药学院, Universitat De València, C. del Cementerio, 1, 46100, Burjassot, Valencia, Spain
Varsenik Harutyunyan Jaghatspanyan & Garnik Harutyunyan
埃里温国立医科大学普通医学院，2 Koryun St, 0025, Yerevan, Armenia
艾玛·马蒂罗相
Consorcio Hospital General Universitario de Valencia, Av. de les Tres Creus, 2, 46014, 瓦伦西亚, 西班牙
罗莎·伊莎贝尔·贝尼特斯·贝尔梅霍
Erebouni Medical Center, Titogradyan St. 14, 0087, Yerevan, Armenia
阿门·瓦罗相
俄亥俄州立大学韦克斯纳医学中心麻醉科临床部，N411 Doan Hall, 410 West 10th Avenue, Columbus, OH, 43210, USA
苏伦·索霍莫尼扬

作者

Gurgen Harutyunyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Varsenik Harutyunyan Jaghatspanyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Emma Martirosyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Rosa Isabel Benitez Bermejo查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Garnik Harutyunyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Andrés Sánchez Gimeno查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Pau Ignasi García Zapata查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Armen Varosyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者
Suren Soghomonyan查看作者的出版物
您也可以在PubMed Google Scholar中搜索该作者

贡献

GH、VHJ、ASG 和 PIGZ 撰写了手稿；SS、GH、EM、AV 和 RIBB 严格修改了手稿。所有作者都阅读并批准了手稿。

通讯作者

与 Gurgen Harutyunyan 的通信。

伦理批准和同意参与

不适用。

利益争夺

作者声明他们没有相互竞争的利益。

出版商注

Springer Nature 对出版地图和机构附属机构的管辖权主张保持中立。

开放存取本文根据知识共享署名 4.0 国际许可进行许可，该许可允许以任何媒介或格式使用、共享、改编、分发和复制，只要您对原作者和来源给予适当的信任，并提供链接到知识共享许可，并说明是否进行了更改。本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果文章的知识共享许可中未包含材料，并且您的预期用途不受法律法规的允许或超出允许的用途，则您需要直接从版权所有者那里获得许可。要查看此许可证的副本，请访问 http://creativecommons.org/licenses/by/4.0/。

转载和许可