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Anstalt \u00f6ffentlichen Rechts"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Improving intestinal tissue integrity appears to be crucial for maintaining global homeostasis in patients suffering from hemorrhagic shock. Since depletion of regional oxygen reserve might lead to cell death and tissue injury, the maintenance of regional tissue oxygenation appears to prevent intestinal mucosa from barrier shut down. Pyrrolidine dithiocarbamate (PDTC), an inducer of heme oxygenase-1 (HO-1), was reported to improve tissue integrity in various tissues under conditions of restricted oxygen delivery. Therefore, we investigated the effect of PDTC pretreatment on intestinal microvascular oxygenation (\u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      ) as a measure of regional tissue oxygen reserve in a rat model of hemorrhagic shock with subsequent shed blood transfusion. Furthermore, we explored whether the effect of systemic PDTC pretreatment on intestinal \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      is associated with alterations in microvascular and mitochondrial function, as well as heme oxygenase-1 (HO-1) protein expression in the intestine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      40 male Wistar rats were randomized into 4 experimental groups and received standardized instrumentation under general anesthesia. Hemorrhagic shock was induced by arterial blood withdrawal (MAP: 40\u2009\u00b1\u20095 mmHg; 1\u00a0h). Subsequently, shed blood was transfused and animals were observed for 2\u00a0h. Control animals were observed for 3\u00a0h without the induction of hemorrhagic shock. PDTC (100\u00a0mg\u00b7kg\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      , i.p.) or saline was applied 24\u00a0h prior to hemorrhagic shock or control treatment. \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      of the ileum and the colon was continuously evaluated by white-light spectrophotometry. Variables of microvascular blood flow, microvascular diffusion distance and mitochondrial respiration were determined by laser Doppler flowmetry as well as incident dark-field imaging and respirometry. HO-1 protein expression was assessed by western blot analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hemorrhagic shock decreased intestinal \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      . Whereas systemic PDTC application did not increase \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      under physiological conditions, pharmacological pretreatment significantly improved colonic \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      after 60\u00a0min of hemorrhagic shock and accelerated early recovery of ileal and colonic \u00b5HbO\n                      <jats:sub>2<\/jats:sub>\n                      . This observation was independent of microvascular perfusion and mitochondrial respiration. PDTC pretreatment led to an increase of relative HO-1 protein expression in the ileum without a significant effect on colonic protein expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The gastrointestinal tract is at persistent risk to develop tissue injury during hemorrhagic shock. The systemic application of PDTC is a promising pharmacological strategy to improve intestinal oxygen reserve during hemorrhagic shock and subsequent blood transfusion. This might lead to reduced intestinal tissue injury, maintain global homeostasis and reduce morbidity of patients suffering from hemorrhagic shock. However, the exact mechanism by which PDTC pretreatment improves intestinal oxygen reserve has to be elucidated in further studies since neither microvascular nor mitochondrial function was altered after PDTC application in this study. Furthermore, observed effects might include both HO-1-dependent and HO-1-independent mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07413-2","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T13:45:34Z","timestamp":1763041534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pyrrolidine dithiocarbamate accelerates early recovery of intestinal microvascular oxygenation in a reversible model of hemorrhagic shock in rats"],"prefix":"10.1186","volume":"23","author":[{"given":"Stefan","family":"Hof","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandra","family":"Kr\u00fcll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kuebart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Herminghaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Relja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Picker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Truse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"issue":"4","key":"7413_CR1","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1056\/NEJMra1705649","volume":"378","author":"JW Cannon","year":"2018","unstructured":"Cannon JW. 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