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Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model
  1. Ryo Hashimoto1,
  2. Mitsutomo Kohno1,
  3. Kana Oiwa1,
  4. Hiroto Onozawa1,
  5. Masazumi Watanabe2,
  6. Hirohisa Horinouchi3,
  7. Hiromi Sakai4,
  8. Koichi Kobayashi2 and
  9. Masayuki Iwazaki1
  1. 1Division of General Thoracic Surgery, Department of Surgery, Tokai University—Isehara Campus, Isehara, Kanagawa, Japan
  2. 2General Thoracic Surgery, Keio University School of Medicine Graduate School of Medicine, Shinjuku-ku, Tokyo, Japan
  3. 3General Thoracic Surgery, Saitama City Hospital, Saitama, Japan
  4. 4Chemistry, Nara Medical University, Kashihara, Nara, Japan
  1. Correspondence to Dr Mitsutomo Kohno; kohno{at}


Background Haemoglobin vesicles (HbVs) are red blood cell (RBC) substitutes with a phospholipid bilayer membrane and a polyethylene modified surface (diameter=250 nm; P50=28 Torr). They can be preserved for years and can be used in patients of all blood types without the risk of infection. Their oxygen affinity can be modified by changing the allosteric effectors.

Methods Left pneumonectomy was performed under mechanical ventilation on rats, followed by rapid exsanguination of ~30% of the total circulating blood volume. Rat RBCs shed in 5% human serum albumin (HSA) solution (rat RBC), HbV with high oxygen affinity in 5% albumin solution (low-P50 HbV, P50=9 Torr), normal HbV suspended in 5% albumin (HbV, P50=28 Torr) or 5% HSA was infused for resuscitation. Haemodynamics and oxygenation were evaluated.

Results Systemic arterial blood pressure significantly decreased after exsanguination and increased after each infusion. In the HbV, low-P50 HbV and rat RBC groups, all rats were liberated from mechanical ventilation and blood pressure was stabilised, whereas 50% of the rats in the HSA group died within 1 hour after weaning from mechanical ventilation. The PaO2 in arterial blood for 1 hour after liberation from mechanical ventilation in the rat RBC, HbV and low-P50 HbV groups was 59.4±12.5, 58.3±10.1 and 70.5±14.5 mm Hg, respectively. The PaO2 in the low-P50 HbV group was significantly higher than those in the rat RBC and HbV groups (p=0.05 for both). Serum lactate elevations due to hypoxic damage were minimised by HbV, low-P50 HbV as well as rat RBCs.

Conclusions The oxygen-carrying ability of HbV was comparable to that of rat RBCs, even under impaired lung function after pneumonectomy. HbVs with high oxygen affinity may have more beneficial effects on oxygenation in pulmonary resection.

  • thoracic surgery

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  • Presented at This study was previously presented as an abstract at the 25th European Conference on General Thoracic Surgery. This study has been also presented as an abstract at the 26th Annual Meeting of the Society of Blood Substitutes, Japan.

  • Contributors Conceptualisation: MK, MW, HH, KK. Funding acquisition: MK, HS. Investigation: RH, MK, KO, HO. Methodology: MK, HH. Resources: HS. Formal analysis: RH, MK. Supervision: HS, KK, MI. Validation: MK. Visualisation: MK. Writing—original draft: RH. Writing—review and editing: MK.

  • Funding This work was supported by Grants Promoting Clinical Trials for Development of New Drugs and Medical Devices from Japan Agency for Medical Research and Development (Grant Number 18lk1403022h0001 to HS and MK), and by a Grant-in-Aid for Fundamental Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 25462183 to MK).

  • Competing interests HS is an inventor on patents related to the production and utilisation of haemoglobin vesicles.

  • Patient consent for publication Not required.

  • Ethics approval All procedures described in this report were approved by the Animal Experimentation Committee of Tokai University (Protocol No. 184044).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. No additional data are available.

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