{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:08:48Z","timestamp":1787317728611,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU FP7 Health Programme","award":["602706"],"award-info":[{"award-number":["602706"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Elevated circulating cardiac troponin T (cTnT) is frequent in septic shock patients. Signs of myocardial ischemia and myocyte necrosis are not universally present, but the precise mechanism for elevated cTnT is unknown. We investigated plasma and heart tissue metabolites concentration in six septic shock (SS) and three sham swine undergoing a protocol of polymicrobial septic shock and resuscitation, in order to highlight possible pathways and biomarkers involved in troponin release (high sensitive cardiac troponin T, hs-cTnT). The animals were divided into two groups: the high cTnT group (n = 3) were pigs showing a significantly higher concentration of cTnT and lactate after resuscitation; the low cTnT group (n = 6, three sham and three septic shock) characterized by a lower value of cTnT and a lactate level &lt; 2 mmol\/L. Spearman correlation was assessed on plasma fold-change of cTnT, cytokines (TNF-\u03b1 and IL-10), and metabolites. Finally, the fold-change between the end of resuscitation and baseline values (Res.\/BL) of plasma metabolites was used to perform a partial least square discriminant analysis (PLS-DA) with three latent variables. Before building the model, the number of features was reduced by summing up the metabolites of the same class that resulted similarly correlated to cTnT fold-change. Proline and glycine were significantly higher in the high cTnT group at the end of experiment both in the myocardium and plasma analyses. Moreover, plasma proline fold-change was found to be positively correlated with cTnT and cytokine fold-changes, and trans-4-hydroxyproline (t4-OH-Pro) fold-change was positively correlated with cTnT fold-change. The PLS-DA model was able to separate the two groups and, among the first ranked features based on VIP score, we found sugars, t4-OH-Pro, proline, creatinine, total amount of sphingomyelins, and glycine. Proline, t4-OH-Pro, and glycine are very abundant in collagen, and our results may suggest that collagen degradation could represent a possible mechanism contributing to septic myocardial injury. The common phenotype of septic cardiomyopathy could be associated to dysregulated collagen metabolism and\/or degradation, further exacerbated by higher inflammation and oxidative stress.<\/jats:p>","DOI":"10.3390\/metabo12040319","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1281-543X","authenticated-orcid":false,"given":"Bernardo","family":"Bollen Pinto","sequence":"first","affiliation":[{"name":"Department of Acute Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Geneva Perioperative Basic, Translational and Clinical Research Group, Geneva University Hospitals, 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7371-3624","authenticated-orcid":false,"given":"Manuela","family":"Ferrario","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-0208","authenticated-orcid":false,"given":"Antoine","family":"Herpain","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme University Hospital\u2014Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Experimental Laboratory of Intensive Care\u2014Erasme University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Brunelli","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-7207","authenticated-orcid":false,"given":"Karim","family":"Bendjelid","sequence":"additional","affiliation":[{"name":"Department of Acute Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"},{"name":"Department of Anesthesiology, Pharmacology and Intensive Care, Geneva Hemodynamic Research Group, Geneva University Hospitals, 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-2847","authenticated-orcid":false,"given":"Marta","family":"Carrara","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5097-600X","authenticated-orcid":false,"given":"Roberta","family":"Pastorelli","sequence":"additional","affiliation":[{"name":"Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13054-018-2043-8","article-title":"Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: A review of the literature","volume":"22","author":"Ehrman","year":"2018","journal-title":"Crit. 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