Skip to main content
Top
Published in: Journal of Anesthesia 2/2020

01-04-2020 | Shock | Original Article

1.2% Hydrogen gas inhalation protects the endothelial glycocalyx during hemorrhagic shock: a prospective laboratory study in rats

Authors: Tsunehisa Sato, Soichiro Mimuro, Takasumi Katoh, Tadayoshi Kurita, Sang Kien Truong, Kensuke Kobayashi, Hiroshi Makino, Matsuyuki Doi, Yoshiki Nakajima

Published in: Journal of Anesthesia | Issue 2/2020

Login to get access

Abstract

Purpose

Hydrogen gas (H2) inhalation improved the survival rate of hemorrhagic shock. However, its mechanisms are unknown. We hypothesized that H2 protected the endothelial glycocalyx during hemorrhagic shock and prolonged survival time.

Methods

83 Sprague–Dawley rats were anesthetized with isoflurane. The animals were randomly assigned to 5 groups: room air with no shock, 1.2% H2 with no shock, room air with shock (Control-S), 1.2% H2 with shock (H21.2%-S), and 3.0% H2 with shock (H23.0%-S). Shock groups were bled to a mean arterial pressure of 30–35 mmHg and held for 60 min, then resuscitated with normal saline at fourfold the amount of the shed blood volume.

Results

The syndecan-1 level was significantly lower in the H21.2%-S [8.3 ± 6.6 ng/ml; P = 0.01; 95% confidence interval (CI), 3.2–35.8] than in the Control-S (27.9 ± 17.0 ng/ml). The endothelial glycocalyx was significantly thicker in the H21.2%-S (0.15 ± 0.02 µm; P = 0.007; 95% CI, 0.02–0.2) than in the Control-S (0.06 ± 0.02 µm). The survival time was longer in the H21.2%-S (327 ± 67 min, P = 0.0160) than in the Control-S (246 ± 69 min). The hemoglobin level was significantly lower in the H21.2%-S (9.4 ± 0.5 g/dl; P = 0.0034; 95% CI, 0.6–2.9) than in the Control-S (11.1 ± 0.8 g/dl). However, the H23.0%-S was not significant.

Conclusions

Inhalation of 1.2% H2 gas protected the endothelial glycocalyx and prolonged survival time during hemorrhagic shock. Therapeutic efficacy might vary depending on the concentration.
Literature
1.
go back to reference Kawashima Y, Irita K, Morita K, Tuzaki K, Sawa T. Preoperative hemorrhagic shock and intraoperative bleeding: two main causes of surgical deaths in Japan. J Jpn Soc Blood Trans. 2005;51(1):23–31.CrossRef Kawashima Y, Irita K, Morita K, Tuzaki K, Sawa T. Preoperative hemorrhagic shock and intraoperative bleeding: two main causes of surgical deaths in Japan. J Jpn Soc Blood Trans. 2005;51(1):23–31.CrossRef
2.
go back to reference Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, Ko TC, Paredes A. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011;112(6):1289–95.CrossRef Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, Ko TC, Paredes A. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011;112(6):1289–95.CrossRef
3.
go back to reference Chappell D, Westphal M, Jacob M. The impact of the glycocalyx on microcirculatory oxygen distribution in critical illness. Curr Opin Anaesthesiol. 2009;22(2):155–62.CrossRef Chappell D, Westphal M, Jacob M. The impact of the glycocalyx on microcirculatory oxygen distribution in critical illness. Curr Opin Anaesthesiol. 2009;22(2):155–62.CrossRef
4.
go back to reference Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y, Miyazaki N, Tsujimoto A, Muraki I, Ando Y, Zaikokuji R, Matsumoto A, Kitagaki H, Tamaoki Y, Usui T, Doi T, Yoshida T, Yoshida S, Ushikoshi H, Toyoda I, Ogura S. Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions. Crit Care. 2017;21(1):261.CrossRef Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y, Miyazaki N, Tsujimoto A, Muraki I, Ando Y, Zaikokuji R, Matsumoto A, Kitagaki H, Tamaoki Y, Usui T, Doi T, Yoshida T, Yoshida S, Ushikoshi H, Toyoda I, Ogura S. Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions. Crit Care. 2017;21(1):261.CrossRef
5.
go back to reference Rubio-Gayosso I, Platts SH, Duling BR. Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2006;290(6):H2247–H2256256.CrossRef Rubio-Gayosso I, Platts SH, Duling BR. Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2006;290(6):H2247–H2256256.CrossRef
6.
go back to reference Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost. 2019;17(2):283–94.CrossRef Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thromb Haemost. 2019;17(2):283–94.CrossRef
7.
go back to reference Diebel ME, Martin JV, Liberati DM, Diebel LN. The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation. J Trauma Acute Care Surg. 2018;84(1):75–80.CrossRef Diebel ME, Martin JV, Liberati DM, Diebel LN. The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation. J Trauma Acute Care Surg. 2018;84(1):75–80.CrossRef
8.
go back to reference Kazuma S, Tokinaga Y, Kimizuka M, Azumaguchi R, Hamada K, Yamakage M. Sevoflurane promotes regeneration of the endothelial glycocalyx by upregulating sialyltransferase. J Surg Res. 2019;241:40–7.CrossRef Kazuma S, Tokinaga Y, Kimizuka M, Azumaguchi R, Hamada K, Yamakage M. Sevoflurane promotes regeneration of the endothelial glycocalyx by upregulating sialyltransferase. J Surg Res. 2019;241:40–7.CrossRef
9.
go back to reference Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688–94.CrossRef Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688–94.CrossRef
10.
go back to reference Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen—comprehensive review of 321 original articles. Med Gas Res. 2015;5:12.CrossRef Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K. Beneficial biological effects and the underlying mechanisms of molecular hydrogen—comprehensive review of 321 original articles. Med Gas Res. 2015;5:12.CrossRef
11.
go back to reference Xie K, Liu L, Yu Y, Wang G. Hydrogen gas presents a promising therapeutic strategy for sepsis. Biomed Res Int. 2014;2014:807635.PubMedPubMedCentral Xie K, Liu L, Yu Y, Wang G. Hydrogen gas presents a promising therapeutic strategy for sepsis. Biomed Res Int. 2014;2014:807635.PubMedPubMedCentral
12.
go back to reference Yu Y, Yang Y, Bian Y, Li Y, Liu L, Zhang H, Xie K, Wang G, Yu Y. Hydrogen gas protects against intestinal injury in wild type but not NRF2 knockout mice with severe sepsis by regulating HO-1 and HMGB1 release. Shock. 2017;48(3):364–70.CrossRef Yu Y, Yang Y, Bian Y, Li Y, Liu L, Zhang H, Xie K, Wang G, Yu Y. Hydrogen gas protects against intestinal injury in wild type but not NRF2 knockout mice with severe sepsis by regulating HO-1 and HMGB1 release. Shock. 2017;48(3):364–70.CrossRef
13.
go back to reference Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T. Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice. Anesthesiology. 2013;118(1):105–13.CrossRef Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T. Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice. Anesthesiology. 2013;118(1):105–13.CrossRef
14.
go back to reference Shinbo T, Kokubo K, Sato Y, Hagiri S, Hataishi R, Hirose M, Kobayashi H. Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart. Am J Physiol Heart Circ Physiol. 2013;305(4):H542–H550550.CrossRef Shinbo T, Kokubo K, Sato Y, Hagiri S, Hataishi R, Hirose M, Kobayashi H. Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart. Am J Physiol Heart Circ Physiol. 2013;305(4):H542–H550550.CrossRef
15.
go back to reference Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Ohta S, Fukuda K, Hori S. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation. 2014;130(24):2173–80.CrossRef Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Ohta S, Fukuda K, Hori S. Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation. 2014;130(24):2173–80.CrossRef
16.
go back to reference Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30–5.CrossRef Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun. 2008;373(1):30–5.CrossRef
17.
go back to reference Matsuoka T, Suzuki M, Sano M, Hayashida K, Tamura T, Homma K, Fukuda K, Sasaki J. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017;83(3):469–75.CrossRef Matsuoka T, Suzuki M, Sano M, Hayashida K, Tamura T, Homma K, Fukuda K, Sasaki J. Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg. 2017;83(3):469–75.CrossRef
18.
go back to reference Kataoka H, Ushiyama A, Akimoto Y, Matsubara S, Kawakami H, Iijima T. Structural behavior of the endothelial glycocalyx is associated with pathophysiologic status in septic mice: an integrated approach to analyzing the behavior and function of the glycocalyx using both electron and fluorescence intravital microscopy. Anesth Analg. 2017;125(3):874–83.CrossRef Kataoka H, Ushiyama A, Akimoto Y, Matsubara S, Kawakami H, Iijima T. Structural behavior of the endothelial glycocalyx is associated with pathophysiologic status in septic mice: an integrated approach to analyzing the behavior and function of the glycocalyx using both electron and fluorescence intravital microscopy. Anesth Analg. 2017;125(3):874–83.CrossRef
19.
go back to reference Kobayashi K, Mimuro S, Sato T, Kobayashi A, Kawashima S, Makino H, Doi M, Katoh T, Nakajima Y. Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model. J Anesth. 2018;32(6):880–5. Kobayashi K, Mimuro S, Sato T, Kobayashi A, Kawashima S, Makino H, Doi M, Katoh T, Nakajima Y. Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model. J Anesth. 2018;32(6):880–5.
20.
go back to reference van den Berg BM, Vink H, Spaan JA. The endothelial glycocalyx protects against myocardial edema. Circ Res. 2003;92(6):592–4.CrossRef van den Berg BM, Vink H, Spaan JA. The endothelial glycocalyx protects against myocardial edema. Circ Res. 2003;92(6):592–4.CrossRef
21.
go back to reference Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116(17):1896–906.CrossRef Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116(17):1896–906.CrossRef
22.
go back to reference Becker BF, Chappell D, Bruegger D, Annecke T, Jacob M. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc Res. 2010;87(2):300–10.CrossRef Becker BF, Chappell D, Bruegger D, Annecke T, Jacob M. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc Res. 2010;87(2):300–10.CrossRef
23.
go back to reference Tamura T, Hayashida K, Sano M, Onuki S, Suzuki M. Efficacy of inhaled HYDROGEN on neurological outcome following BRAIN ischemia during post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial. Trials. 2017;18(1):488.CrossRef Tamura T, Hayashida K, Sano M, Onuki S, Suzuki M. Efficacy of inhaled HYDROGEN on neurological outcome following BRAIN ischemia during post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial. Trials. 2017;18(1):488.CrossRef
24.
go back to reference Kohama K, Yamashita H, Aoyama-Ishikawa M, Takahashi T, Billiar TR, Nishimura T, Kotani J, Nakao A. Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation. Surgery. 2015;158(2):399–407.CrossRef Kohama K, Yamashita H, Aoyama-Ishikawa M, Takahashi T, Billiar TR, Nishimura T, Kotani J, Nakao A. Hydrogen inhalation protects against acute lung injury induced by hemorrhagic shock and resuscitation. Surgery. 2015;158(2):399–407.CrossRef
25.
go back to reference Du Z, Liu J, Jia H, Xu W, Zhao X. Three hydrogen-rich solutions protect against intestinal injury in uncontrolled hemorrhagic shock. Int J Clin Exp Med. 2015;8(5):7620–6.PubMedPubMedCentral Du Z, Liu J, Jia H, Xu W, Zhao X. Three hydrogen-rich solutions protect against intestinal injury in uncontrolled hemorrhagic shock. Int J Clin Exp Med. 2015;8(5):7620–6.PubMedPubMedCentral
26.
go back to reference Du Z, Jia H, Liu J, Zhao X, Xu W. Effects of three hydrogen-rich liquids on hemorrhagic shock in rats. J Surg Res. 2015;193(1):377–82.CrossRef Du Z, Jia H, Liu J, Zhao X, Xu W. Effects of three hydrogen-rich liquids on hemorrhagic shock in rats. J Surg Res. 2015;193(1):377–82.CrossRef
27.
go back to reference Aguirre JA, Lucchinetti E, Clanachan AS, Plane F, Zaugg M. Unraveling interactions between anesthetics and the endothelium: update and novel insights. Anesth Analg. 2016;122(2):330–48.CrossRef Aguirre JA, Lucchinetti E, Clanachan AS, Plane F, Zaugg M. Unraveling interactions between anesthetics and the endothelium: update and novel insights. Anesth Analg. 2016;122(2):330–48.CrossRef
28.
go back to reference Iba T. Glycocalyx regulates the intravascular hemostasis. Juntendo Med J. 2016;62(4):330–5.CrossRef Iba T. Glycocalyx regulates the intravascular hemostasis. Juntendo Med J. 2016;62(4):330–5.CrossRef
29.
go back to reference Osuka A, Kusuki H, Yoneda K, Matsuura H, Matsumoto H, Ogura H, Ueyama M. Glycocalyx shedding is enhanced by age and correlates with increased fluid requirement in patients with major burns. Shock. 2018;50(1):60–5.CrossRef Osuka A, Kusuki H, Yoneda K, Matsuura H, Matsumoto H, Ogura H, Ueyama M. Glycocalyx shedding is enhanced by age and correlates with increased fluid requirement in patients with major burns. Shock. 2018;50(1):60–5.CrossRef
30.
go back to reference Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, Ohta S. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016;6:18971.CrossRef Iuchi K, Imoto A, Kamimura N, Nishimaki K, Ichimiya H, Yokota T, Ohta S. Molecular hydrogen regulates gene expression by modifying the free radical chain reaction-dependent generation of oxidized phospholipid mediators. Sci Rep. 2016;6:18971.CrossRef
31.
go back to reference Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol. 2009;104(1):78–89.CrossRef Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol. 2009;104(1):78–89.CrossRef
32.
go back to reference van Bommel J, Siegemund M, Henny ChP, Ince C. Heart, kidney, and intestine have different tolerances for anemia. Transl Res. 2008;151(2):110–7.CrossRef van Bommel J, Siegemund M, Henny ChP, Ince C. Heart, kidney, and intestine have different tolerances for anemia. Transl Res. 2008;151(2):110–7.CrossRef
33.
go back to reference Bihorac A, Delano MJ, Schold JD, Lopez MC, Nathens AB, Maier RV, Layon AJ, Baker HV, Moldawer LL. Incidence, clinical predictors, genomics, and outcome of acute kidney injury among trauma patients. Ann Surg. 2010;252(1):158–65.CrossRef Bihorac A, Delano MJ, Schold JD, Lopez MC, Nathens AB, Maier RV, Layon AJ, Baker HV, Moldawer LL. Incidence, clinical predictors, genomics, and outcome of acute kidney injury among trauma patients. Ann Surg. 2010;252(1):158–65.CrossRef
34.
go back to reference Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015;19:26.CrossRef Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015;19:26.CrossRef
35.
go back to reference Kurita T, Morita K, Fukuda K, Uraoka M, Takata K, Sanjo Y, Sato S. Influence of hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane in a swine model. Anesthesiology. 2005;103(6):1189–94.CrossRef Kurita T, Morita K, Fukuda K, Uraoka M, Takata K, Sanjo Y, Sato S. Influence of hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane in a swine model. Anesthesiology. 2005;103(6):1189–94.CrossRef
36.
go back to reference Nakajima Y, Moriwaki G, Ikeda K, Fujise Y. The effects of sevoflurane on recovery of brain energy metabolism after cerebral ischemia in the rat: a comparison with isoflurane and halothane. Anesth Analg. 1997;85(3):593–9.CrossRef Nakajima Y, Moriwaki G, Ikeda K, Fujise Y. The effects of sevoflurane on recovery of brain energy metabolism after cerebral ischemia in the rat: a comparison with isoflurane and halothane. Anesth Analg. 1997;85(3):593–9.CrossRef
Metadata
Title
1.2% Hydrogen gas inhalation protects the endothelial glycocalyx during hemorrhagic shock: a prospective laboratory study in rats
Authors
Tsunehisa Sato
Soichiro Mimuro
Takasumi Katoh
Tadayoshi Kurita
Sang Kien Truong
Kensuke Kobayashi
Hiroshi Makino
Matsuyuki Doi
Yoshiki Nakajima
Publication date
01-04-2020
Publisher
Springer Singapore
Published in
Journal of Anesthesia / Issue 2/2020
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-020-02737-3

Other articles of this Issue 2/2020

Journal of Anesthesia 2/2020 Go to the issue