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To enhance the practical feasibility and efficacy of the system, we integrated a minimally invasive CO monitor and a closed-loop control of vasopressin (AVP) infusion to the system and validated the integrated system in dogs with endotoxin-induced shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Based on the circulatory equilibrium framework, the system directly controls systemic vascular resistance and stressed blood volume by titrating NE and Ringer\u2019s acetate solution (RiA), respectively, thereby restoring AP and CO. AVP is automatically initiated once infusion rate of NE is increased higher than 1\u00a0\u03bcg\u00b7kg\u207b\n                      <jats:sup>1<\/jats:sup>\n                      \u00b7min\u207b\n                      <jats:sup>1<\/jats:sup>\n                      . The minimally invasive CO monitor estimates CO (CO\n                      <jats:sub>es<\/jats:sub>\n                      ) by a machine-learning analysis of the peripheral AP contour. In eight anesthetized dogs, the system was implemented, and reference CO (CO\n                      <jats:sub>ref<\/jats:sub>\n                      ) was measured using an aortic flow probe to calibrate CO\n                      <jats:sub>es<\/jats:sub>\n                      and track reference hemodynamics. Endotoxin shock was induced via intravenous lipopolysaccharide infusions. After the target AP and CO\n                      <jats:sub>es<\/jats:sub>\n                      were set to 70\u00a0mmHg and 132 (132\u2013133) mL\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively, the system was activated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The lipopolysaccharide infusion significantly reduced AP from 82 (80\u201385) to 52 (50\u201356) mmHg and CO\n                      <jats:sub>ref<\/jats:sub>\n                      from 132 (125\u2013146) to 90 (80\u2013103) mL\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , and increased the blood lactate level (LAC) from 21 (21\u201323) to 36 (32\u201338) mg\u00b7dL\n                      <jats:sup>\u22121<\/jats:sup>\n                      . Once the system was activated, infusions of NE and RiA were automatically initiated. Infusion of AVP initiated during the system control was associated with significant reduction in NE dose while maintaining AP. Within 5\u00a0min after system activation, AP and CO\n                      <jats:sub>es<\/jats:sub>\n                      were recovered to &gt;65\u00a0mmHg and &gt;122 (122\u2013123) ml\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively. The median absolute performance errors for AP and CO\n                      <jats:sub>es<\/jats:sub>\n                      were &lt;5%. At 60\u00a0min after system activation, AP and CO\n                      <jats:sub>ref<\/jats:sub>\n                      significantly increased to 72 (68\u201375) mmHg and 130 (127\u2013137) ml\u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      and LAC significantly decreased to 26 (25\u201328) mg\u00b7dL\n                      <jats:sup>\u22121<\/jats:sup>\n                      relative to the values observed at endotoxin shock. CO\n                      <jats:sub>es<\/jats:sub>\n                      tracked directional changes in CO\n                      <jats:sub>ref<\/jats:sub>\n                      reasonably well.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This proof-of-concept study validates the feasibility and physiological performance of the system for the hemodynamic management of vasoplegic shock.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40635-026-00977-3","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:25:51Z","timestamp":1789874751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Automated hemodynamic resuscitation system for computer-controlled norepinephrine, vasopressin, and fluid therapy in endotoxin-induced shock: a feasibility and physiological proof-of-concept study"],"prefix":"10.1186","volume":"14","author":[{"given":"Kazumasu","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-4702","authenticated-orcid":false,"given":"Kazunori","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Ohba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Otake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Hiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Fukumitsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sunagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Joe","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Saku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"2","key":"977_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.bjae.2024.10.004","volume":"25","author":"RN Mistry","year":"2025","unstructured":"Mistry RN, Winearls JE (2025) Management of vasoplegic shock. 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All experimental procedures were conducted in accordance with the Guidelines for Animal Experiments established by the Japanese Ministry of Health, Labour and Welfare.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Toru Kawada has received consulting fees from NTT Research, Inc. Yasuyuki Kataoka and Joe Alexander Jr are employees of NTT Research, Inc. Keita Saku has received research funding from Abiomed Inc., NTT Research, Inc., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals Inc., and Zeon Medical Inc.; and honoraria from Abiomed Japan K.K. and Mallinckrodt Pharma K.K.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"124"}}