Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model

Mitsutomo Kohno, Tatsuhiko Ikeda, Ryo Hashimoto, Yotaro Izumi, Masazumi Watanabe, Hirohisa Horinouchi, Hiromi Sakai, Koichi Kobayashi, Masayuki Iwazaki

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Abstract

Objectives Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. Methods Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer’s solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. Results In the HbV/rHSA and mRBC/rHSA groups, all mice survived 7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. Conclusions The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

Original languageEnglish
Article numbere0178724
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

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Pneumonectomy
hemoglobin
Hemoglobins
erythrocytes
Serum Albumin
animal models
mice
Blood
Blood Substitutes
Hypoxia-Inducible Factor 1
Recovery
blood volume
lung function
Erythrocyte Transfusion
Phospholipids
Intraoperative Complications
Cells
Blood Volume
Oxygen
phospholipids

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kohno, M., Ikeda, T., Hashimoto, R., Izumi, Y., Watanabe, M., Horinouchi, H., ... Iwazaki, M. (2017). Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model. PLoS One, 12(6), [e0178724]. https://doi.org/10.1371/journal.pone.0178724

Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model. / Kohno, Mitsutomo; Ikeda, Tatsuhiko; Hashimoto, Ryo; Izumi, Yotaro; Watanabe, Masazumi; Horinouchi, Hirohisa; Sakai, Hiromi; Kobayashi, Koichi; Iwazaki, Masayuki.

In: PLoS One, Vol. 12, No. 6, e0178724, 01.06.2017.

Research output: Contribution to journalArticle

Kohno, M, Ikeda, T, Hashimoto, R, Izumi, Y, Watanabe, M, Horinouchi, H, Sakai, H, Kobayashi, K & Iwazaki, M 2017, 'Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model', PLoS One, vol. 12, no. 6, e0178724. https://doi.org/10.1371/journal.pone.0178724
Kohno M, Ikeda T, Hashimoto R, Izumi Y, Watanabe M, Horinouchi H et al. Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model. PLoS One. 2017 Jun 1;12(6). e0178724. https://doi.org/10.1371/journal.pone.0178724
Kohno, Mitsutomo ; Ikeda, Tatsuhiko ; Hashimoto, Ryo ; Izumi, Yotaro ; Watanabe, Masazumi ; Horinouchi, Hirohisa ; Sakai, Hiromi ; Kobayashi, Koichi ; Iwazaki, Masayuki. / Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model. In: PLoS One. 2017 ; Vol. 12, No. 6.
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abstract = "Objectives Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40{\%} exchange-transfusion with HbVs. Methods Before performing left pneumonectomies, 40{\%} of the blood volume of mice was replaced with a) lactated Ringer’s solution (control), b) 5{\%} recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. Results In the HbV/rHSA and mRBC/rHSA groups, all mice survived 7 days after pneumonectomy, whereas 100{\%} of the control mice died within a few h and 50{\%} of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. Conclusions The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.",
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N2 - Objectives Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. Methods Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer’s solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. Results In the HbV/rHSA and mRBC/rHSA groups, all mice survived 7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. Conclusions The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

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