title: Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model.
abstract: Multiorgan failure is a catastrophic consequence of heat stroke (HS) and considered the underlying etiology of mortality. Identifying novel biomarkers capable of predicting the extent of HS-induced organ damage will enhance point-of-care triage and treatment. Conscious male F344 rats (n = 32) were radiotelemetered for continuous core temperature (Tc), heart rate, and arterial pressure measurement. Twenty-two animals were exposed to ambient temperature of 37°C to a maximum Tc of 41.9 ± 0.1°C. Rats were euthanized at 24 h of recovery for analysis of plasma biomarkers [cardiac troponin I (cTnI), blood urea nitrogen (BUN), alanine aminotransferase (ALT), albumin, glucose] and histology. Tc profiles observed during recovery stratified HS severity into Mild, Moderate, and Severe. Eleven (50%) animals exhibited an acute compensatory hemodynamic response to heat exposure and a monophasic Tc profile consisting of sustained hyperthermia (∼1°C). Five (23%) rats displayed hemodynamic challenge and a biphasic Tc profile with rapid return to baseline followed by rebound hyperthermia. All biomarkers were significantly altered from control values (P < 0.05). Four (18%) animals exhibited significant hemodynamic compromise during heat and a triphasic profile characterized by rapid cooling to baseline Tc, rebound hyperthermia, and subsequent hypothermia (∼35°C) through 24 h. cTnI showed a 40-fold increase over CON (P < 0.001) and correlated with BUN (r = 0.912) consistent with cardiorenal failure. Hypoglycemia correlated with ALT (r = 0.824) suggestive of liver dysfunction. Histology demonstrated myocardial infarction, renal tubular necrosis, and acute liver necrosis. Two (9%) animals succumbed during HS recovery. This study identified novel biomarkers that predict HS severity and organ damage during acute recovery that could provide clinical significance for identifying key biomarkers of HS pathogenesis.
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts carrie.m.quinn.mil@mail.mil.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Quinn
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.
authors.forename: Rocio M
authors.initials: RM
authors.lastname: Duran
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Audet
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.
authors.forename: Nisha
authors.initials: N
authors.lastname: Charkoudian
authors.affiliation: U.S. Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, Massachusetts.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Leon
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000502:physiology*; D015415:Biomarkers; D001831:Body Temperature / Q000502:physiology*; D002319:Cardiovascular System / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D018883:Heat Stroke / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012720:Severity of Illness Index; D013686:Telemetry
chemical_list: D015415:Biomarkers
keywords: cardiac troponin I; heat stroke; hemodynamic; thermoregulation