{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T13:19:40Z","timestamp":1778505580871,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T00:00:00Z","timestamp":1726876800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Artificial Organs"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Phase I clinical trial of an artificial oxygen carrier (liposome\u2010encapsulated hemoglobin vesicles [HbVs]) is safely completed, considering the other clinical application. Herein, we aimed to investigate the resuscitation effects of HbVs in cases of lethal hemorrhage, including the mechanisms involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Optical mapping analysis (OMP) and electrophysiological studies (EPS), immunostaining pathological examination for hypoxia\u2010inducible factor\u20101\u03b1 (HIF1\u2010alpha) in the heart tissue, and blood troponin I (TnI) level measurements were performed in rats that underwent five rounds of spontaneous arterial bleeding with up to 65% hemorrhage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten rats in each group were resuscitated by a transvenous infusion of 5% albumin (ALB), washed erythrocytes (wRBC), HbVs (HbV), 50% HbV diluted by 5% albumin (50% HbV), and 66% HbV diluted by 5% albumin (66% HbV). The rats in the ALB and 50% HbV groups died, whereas those in the other groups survived. OMP showed impaired action potential duration dispersion (APDd) in the left ventricle in the ALB and 50% HbV groups, which was attenuated in the other groups. Lethal arrhythmias were provoked by EPS in the ALB and 50% HbV groups but not in the other groups. HIF1\u2010alpha was positively stained only in the ALB and 50% HbV groups. TnI levels were elevated in the ALB and 50% HbV groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Acute lethal hemorrhage causes myocardial ischemia with hypoxia and arrhythmias, which may be induced by impaired APDd and myocardial damage, reflected in the increased levels of HIF1\u2010alpha and TnI. HbVs could be useful for resuscitation and may help save patients with injuries such as gunshot wounds.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aor.14858","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T03:14:26Z","timestamp":1726888466000},"page":"39-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liposome\u2010encapsulated hemoglobin rescues hemorrhagic shock heart through anti\u2010ischemic and anti\u2010arrhythmogenic effects on myocardium in repetitive 65% bleeding rat model"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-6260","authenticated-orcid":false,"given":"Bonpei","family":"Takase","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine National Defense Medical College  Tokorozawa Japan"},{"name":"Division of Cardiology Iruma Heart Hospital  Iruma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Higashimura","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine National Defense Medical College  Tokorozawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine National Defense Medical College  Tokorozawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology National Defense Medical College  Tokorozawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Cardiology National Defense Medical College  Tokorozawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-3032","authenticated-orcid":false,"given":"Hiromi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Medicine Nara Medical University  Nara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007977"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001042"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-023-2706-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001262"},{"key":"e_1_2_8_6_1","first-page":"72","article-title":"Blood volume in rat","volume":"26","author":"Lee HB","year":"1985","journal-title":"J Nucl 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