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However, sustained catecholamine infusion is linked to cardiac toxicity and impaired responsiveness. Several pre-clinical and clinical studies have investigated the use of alternative vasopressors in the treatment of septic shock, with limited benefits and generally no effect on mortality. Apelin-13 (APL-13) is an endogenous positive inotrope and vasoactive peptide and has been demonstrated cardioprotective with vasomodulator and sparing life effects in animal models of septic shock. A primary objective of this study was to evaluate the NE-sparing effect of APL-13 infusion in an experimental sepsis-induced hypotension.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>For this goal, sepsis was induced by cecal ligation and puncture (CLP) in male rats and the arterial blood pressure (BP) monitored continuously via a carotid catheter. Monitoring, fluid resuscitation and experimental treatments were performed on conscious animals. Based on pilot assays, normal saline fluid resuscitation (2.5\u00a0mL\/Kg\/h) was initiated 3\u00a0h post-CLP and maintained up to the endpoint. Thus, titrated doses of NE, with or without fixed-doses of APL-13 or the apelin receptor antagonist F13A co-infusion were started when 20% decrease of systolic BP (SBP) from baseline was achieved, to restore SBP values\u2009\u2265\u2009115\u2009\u00b1\u20091.5\u00a0mmHg (baseline average\u2009\u00b1\u2009SEM).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A reduction in mean NE dose was observed with APL-13 but not F13A co-infusion at pre-determined treatment time of 4.5\u2009\u00b1\u20090.5\u00a0h (17.37\u2009\u00b1\u20091.74\u00a0\u00b5g\/Kg\/h [APL-13] vs. 25.64\u2009\u00b1\u20092.61\u00a0\u00b5g\/Kg\/h [Control NE] vs. 28.60\u2009\u00b1\u20094.79\u00a0\u00b5g\/Kg\/min [F13A], P\u2009=\u20090.0491). A 60% decrease in NE infusion rate over time was observed with APL-13 co-infusion, (<jats:italic>p<\/jats:italic>\u2009=\u20090.008 vs NE alone), while F13A co-infusion increased the NE infusion rate over time by 218% (<jats:italic>p<\/jats:italic>\u2009=\u20090.003 vs NE\u2009+\u2009APL-13). Associated improvements in cardiac function are likely mediated by (i) enhanced left ventricular end-diastolic volume (0.18\u2009\u00b1\u20090.02\u00a0mL [Control NE] vs. 0.30\u2009\u00b1\u20090.03\u00a0mL [APL-13], <jats:italic>P<\/jats:italic>\u2009=\u20090.0051), stroke volume (0.11\u2009\u00b1\u20090.01\u00a0mL [Control NE] vs. 0.21\u2009\u00b1\u20090.01\u00a0mL [APL-13], <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and cardiac output (67.57\u2009\u00b1\u20098.63\u00a0mL\/min [Control NE] vs. 112.20\u2009\u00b1\u20098.53\u00a0mL\/min [APL-13], <jats:italic>P<\/jats:italic>\u2009=\u20090.0036), and (ii) a reduced effective arterial elastance (920.6\u2009\u00b1\u200981.4\u00a0mmHg\/mL\/min [Control NE] vs. 497.633.44\u00a0mmHg\/mL\/min. [APL-13], <jats:italic>P<\/jats:italic>\u2009=\u20090.0002). APL-13 administration was also associated with a decrease in lactate levels compared to animals only receiving NE (7.08\u2009\u00b1\u20090.40 [Control NE] vs. 4.78\u2009\u00b1\u20090.60 [APL-13], <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>APL-13 exhibits NE-sparing benefits in the treatment of sepsis-induced shock, potentially reducing deleterious effects of prolonged exogenous catecholamine administration.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40635-024-00650-7","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T21:02:41Z","timestamp":1722891761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Apelin-13 administration allows for norepinephrine sparing in a rat model of cecal ligation and puncture-induced septic shock"],"prefix":"10.1186","volume":"12","author":[{"given":"William","family":"Salvail","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dany","family":"Salvail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Chagnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2938-4744","authenticated-orcid":false,"given":"Olivier","family":"Lesur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"issue":"10219","key":"650_CR1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","volume":"395","author":"KE Rudd","year":"2020","unstructured":"Rudd KE, Johnson SC, Agesa KM et al (2020) Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study. 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