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This study used a post-hoc, multimodal approach\u2014including single-nucleus RNA sequencing (snRNA-seq), echocardiography, mitochondrial function, and histopathology\u2014to characterize SIC in a non-human primate model. Archived data and samples from six baboons challenged with 37.5 mg\/kg of purified peptidoglycan were analyzed. Vital signs and echocardiography were monitored for 8 hours; the endpoint was survival at 168 hours or euthanasia for irreversible organ failure. Septic shock\u2014defined by hypotension, tachycardia, and elevated lactate\u2014was associated with poor outcomes. Echocardiography showed reduced intravascular volume, contraction, stroke volume, and cardiac index. SnRNA-seq revealed distinct transcriptomic profiles: non-survivors exhibited inflammation, mitochondrial dysfunction, and maladaptive remodeling; survivors showed activation of pathways supporting contraction, metabolism, and repair. Cell-type analysis highlighted metabolic dysfunction in cardiomyocytes, TNF\/NF-\u03baB-driven inflammation in endothelial cells, and stress responses in fibroblasts and pericytes. Mitochondrial analysis showed impaired electron transport and disrupted metabolism. Histopathology revealed inflammation and myofibrillar damage, more severe in non-survivors. This model recapitulates key SIC features and supports mechanistic and therapeutic discovery.<\/jats:p>","DOI":"10.1101\/2025.06.16.659963","type":"posted-content","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T11:30:16Z","timestamp":1750505416000},"source":"Crossref","is-referenced-by-count":0,"title":["Multimodal Analysis of Sepsis-induced Cardiomyopathy in a Baboon Model"],"prefix":"10.64898","author":[{"given":"Tomohiro","family":"Abe","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-6160","authenticated-orcid":false,"given":"Robert","family":"Silasi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi S.","family":"Keshari","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-9885","authenticated-orcid":false,"given":"Narcis","family":"Popescu","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Girija","family":"Regmi","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Aging and Metabolism, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin","family":"Georgescu","sequence":"additional","affiliation":[{"name":"Genes and Human Disease, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2919-3624","authenticated-orcid":false,"given":"Mariko","family":"Kudo","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Lupu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6167-3175","authenticated-orcid":false,"given":"Kenneth","family":"Humphries","sequence":"additional","affiliation":[{"name":"Aging and Metabolism, Oklahoma Medical Research Foundation; Oklahoma City, OK, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe H.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Michale E. 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