{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:52:54Z","timestamp":1791399174999,"version":"4.3.3"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"16","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemorrhagic shock remains a leading cause of mortality due to impaired oxygen delivery following severe blood loss. Hemoglobin-based oxygen carriers (HBOCs) are promising alternatives to red blood cell transfusion; however, their molecular size critically governs nitric oxide (NO) scavenging, vascular reactivity, and overall safety. Here, we systematically evaluated acellular human hemoglobin (hHb) and four polymerized hemoglobin formulations with progressively increasing molecular weights (PolyhHb-10, \u223c1080 kDa; PolyhHb-12, \u223c1200 kDa; PolyhHb-15, \u223c1490 kDa; and PolyhHb-16, \u223c1570 kDa) to define size-dependent determinants of vascular function. Ex vivo, isolated mesenteric arterioles from New Zealand white rabbits were perfused with HBOC\u2212whole blood mixtures (1:0, 1:1, and 1:3) across physiologically relevant flow rates to quantify shear-mediated vasodilation and endothelial function. The acetylcholine challenge was used to probe NO bioavailability. In vivo validation was performed in Golden Syrian hamsters using a dorsal window chamber model to assess microvascular hemodynamics, including the vessel diameter, blood flow, and functional capillary density. PolyhHb-12 consistently preserved endothelial-dependent vasodilation and exhibited minimal NO scavenging across conditions. In contrast, larger polymers (PolyhHb-15 and PolyhHb-16) showed paradoxically increased NO scavenging despite improved capillary perfusion, indicating a trade-off between microcirculatory flow enhancement and endothelial signaling. In vivo, increasing the molecular size yielded diminishing returns in overall hemodynamic stability. Together, these findings identify an intermediate molecular size as optimal for balancing rheological properties, NO bioavailability, and vascular function. PolyhHb-12 emerges as a lead candidate, supporting the design of next-generation HBOCs with improved safety and efficacy for hemorrhagic shock resuscitation.<\/jats:p>","DOI":"10.1021\/acsabm.6c00900","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T07:47:11Z","timestamp":1785138431000},"page":"7582-7593","source":"Crossref","is-referenced-by-count":1,"title":["Optimizing the Hemoglobin-Based Oxygen Carrier Molecular Size to Balance Vascular Function and Hemodynamic Responses after Transfusion"],"prefix":"10.1021","volume":"9","author":[{"given":"Carlos","family":"Munoz","sequence":"first","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0101-4628","authenticated-orcid":true,"given":"Daniela","family":"Lucas","sequence":"additional","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinda","family":"Martinez","sequence":"additional","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-3789","authenticated-orcid":true,"given":"Nathaniel","family":"Ung","sequence":"additional","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4698-2332","authenticated-orcid":true,"given":"Mohd Asim","family":"Khan","sequence":"additional","affiliation":[{"name":"The Ohio State University , , , ,","place":["Columbus, Ohio, United States, 43210-1132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-3920","authenticated-orcid":true,"given":"Tanmay","family":"Salvi","sequence":"additional","affiliation":[{"name":"The Ohio State University , , , ,","place":["Columbus, Ohio, United States, 43210-1132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6367-3046","authenticated-orcid":true,"given":"Griffin J.","family":"Beyer","sequence":"additional","affiliation":[{"name":"The Ohio State University , , , ,","place":["Columbus, Ohio, United States, 43210-1132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre F.","family":"Palmer","sequence":"additional","affiliation":[{"name":"The Ohio State University , , , ,","place":["Columbus, Ohio, United States, 43210-1132"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-2839","authenticated-orcid":true,"given":"Pedro","family":"Cabrales","sequence":"additional","affiliation":[{"name":"University of California San Diego , , , ,","place":["La Jolla, California, United States, 92093-0021"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"issue":"6","key":"2026081707165377500_cit1","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.amjsurg.2016.08.018","article-title":"Time Is the Enemy: Mortality in Trauma Patients with Hemorrhage from Torso Injury Occurs Long before the \u201cGolden Hour\u201d","volume":"212","author":"Alarhayem","year":"2016","journal-title":"Am. 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Trauma Acute Care Surg."},{"key":"2026081707165377500_cit3","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1111\/trf.16528","article-title":"Prehospital Whole Blood Reduces Early Mortality in Patients with Hemorrhagic Shock","volume":"61","author":"Braverman","year":"2021","journal-title":"Transfusion"},{"issue":"S1","key":"2026081707165377500_cit4","doi-asserted-by":"publisher","first-page":"S203","DOI":"10.1111\/trf.16991","article-title":"Nationwide Estimates of the Need for Prehospital Blood Products after Injury","volume":"62","author":"Hashmi","year":"2022","journal-title":"Transfusion"},{"key":"2026081707165377500_cit5","doi-asserted-by":"publisher","first-page":"S286","DOI":"10.1111\/trf.16461","article-title":"More Sophisticated than a Drink Cooler or an Old Sphygmomanometer but Still Not Adequate for Prehospital Blood: A Market Review of Commercially Available Equipment for Prehospital Blood Transport and Administration","volume":"61","author":"Martin","year":"2021","journal-title":"Transfusion"},{"issue":"3","key":"2026081707165377500_cit6","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/voxs.12498","article-title":"The Use of Prehospital Blood Products in the Resuscitation of Trauma Patients: A Review of Prehospital Transfusion Practices and a Description of Our Regional Whole Blood Program in San Antonio, TX","volume":"14","author":"Pokorny","year":"2019","journal-title":"ISBT Sci. 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Physiol."}],"container-title":["ACS Applied Bio Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsabm.6c00900","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/16\/7582\/66251685\/mt-2026-00900z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/16\/7582\/66251685\/mt-2026-00900z.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:23:45Z","timestamp":1786965825000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article\/9\/16\/7582\/5232122\/Optimizing-the-Hemoglobin-Based-Oxygen-Carrier"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":32,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,7,24]]},"published-print":{"date-parts":[[2026,8,17]]}},"URL":"https:\/\/doi.org\/10.1021\/acsabm.6c00900","relation":{},"ISSN":["2576-6422"],"issn-type":[{"value":"2576-6422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}