Resuscitation from hemorrhagic shock by carbon monoxide- and oxygen-carrying capacities of artificial red cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03824
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Nara Medical University
• Principal Investigator: Sakai Hiromi 奈良県立医科大学, 医学部, 教授 (70318830)
• Co-Investigator(Kenkyū-buntansha): 松平 崇 奈良県立医科大学, 医学部, 講師 (20570998) ; 山本 惠三 奈良県立医科大学, 医学部, 准教授 (90254490)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 人工酸素運搬体 / 輸血代替 / 虚血再灌流傷害 / 一酸化炭素 / 蘇生液 / 出血性ショック / リポソーム / DDS

Outline of Final Research Achievements

Artificial red blood cell (HbV) is a promising new pharmaceutic that can complement blood transfusion therapy. When CO-bound HbV was administered to rats in hemorrhagic shock, hemodynamics and blood gas parameters recovered to almost normal values, showing sufficient resuscitation effect. Surprisingly, there were no signs suggesting CO toxicity. In addition, the number of necrotic cells in the cerebral hippocampus was reduced by administration of CO-HbV, demonstrating its effectiveness in reducing ischemia-reperfusion injury. The absence of effects on the central nervous system was confirmed from functional observation battery evaluation, and furthermore, the absence of CO toxicity-induced changes was confirmed from brain hippocampal histopathology. Based on these findings, CO-HbV was considered to be a target for practical application as a new pharmaceutic.

Free Research Field

医工学・生体材料学

Academic Significance and Societal Importance of the Research Achievements

輸血用血液が確保できない状況において、出血性ショック状態の患者に対し緊急的にO2運搬機能のある蘇生液を投与できれば、循環血液量の回復とO2供給量の補充により救命率が格段に向上する。HbVは血液型が無く、感染源も含まず、備蓄ができるので、いつでもどこでも必要時に投与できる。しかし蘇生時に生じる虚血再灌流障害を低減する方策が求められている。COは毒ガスであるが、本研究では、意外にもCO-HbVはCOを徐放し虚血再灌流障害を低減できること、そしてHbVはCO徐放後にO2運搬体として作動することもわかった。毒(CO)をもって毒(ROS)を制する新しい製剤として期待ができる。