{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:46:10Z","timestamp":1787017570139,"version":"build-2736575974"},"reference-count":97,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:p>\n                    It has been suggested that medications can increase heat stroke (HS) susceptibility\/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (T\n                    <jats:sub>c<\/jats:sub>\n                    ) of male, C57BL\/6J mice ( n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg\/kg or high dose (HI) 5 mg\/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4\u00b0C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (T\n                    <jats:sub>c,Max<\/jats:sub>\n                    )], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to T\n                    <jats:sub>c,Max<\/jats:sub>\n                    , thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at T\n                    <jats:sub>c,Max<\/jats:sub>\n                    , HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to increased systemic morbidity.<\/jats:p>","DOI":"10.1152\/japplphysiol.00242.2017","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T21:10:28Z","timestamp":1496956228000},"page":"544-557","source":"Crossref","is-referenced-by-count":15,"title":["Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke"],"prefix":"10.1152","volume":"123","author":[{"given":"Gerald N.","family":"Audet","sequence":"first","affiliation":[{"name":"Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna M.","family":"Dineen","sequence":"additional","affiliation":[{"name":"Thermal and Mountain Medicine 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