{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:27:10Z","timestamp":1775064430632,"version":"3.50.1"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg\n            <jats:sup>2+<\/jats:sup>\n            (ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1\u03b2, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound\/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1\u03b2, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.\n          <\/jats:p>","DOI":"10.1128\/cvi.00390-16","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:22:21Z","timestamp":1472689341000},"page":"863-872","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Small-Volume Adenosine, Lidocaine, and Mg\n            <sup>2+<\/sup>\n            4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics"],"prefix":"10.1128","volume":"23","author":[{"given":"Maddison Jade","family":"Griffin","sequence":"first","affiliation":[{"name":"Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley Louise","family":"Letson","sequence":"additional","affiliation":[{"name":"Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey Phillip","family":"Dobson","sequence":"additional","affiliation":[{"name":"Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2013.04.012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3552"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70112-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70001-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.2762"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31827e83af"},{"key":"e_1_3_2_9_2","article-title":"Characterization of brain-heart interactions in a rodent model of sepsis","author":"Bollen Pinto B","year":"2016","unstructured":"Bollen Pinto B, Ritter C, Michels M, Gambarotta N, Ferrario M, Dal-Pizzol F, Singer M. 26 May 2016. 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