Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model

2014 ◽  
Vol 117 (9) ◽  
pp. 971-978 ◽  
Author(s):  
Carrie M. Quinn ◽  
Rocio M. Duran ◽  
Gerald N. Audet ◽  
Nisha Charkoudian ◽  
Lisa R. Leon
Keyword(s):  
Troponin I ◽  
Point Of Care ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Fold Increase ◽  
Organ Damage ◽  
Stroke Severity ◽  
Conscious Rat ◽  
Novel Biomarkers

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.

Point-of-care cardiac troponin test accurately predicts heat stroke severity in rats

2015 ◽  
Vol 309 (10) ◽  
pp. R1264-R1272 ◽  
Author(s):  
Gerald N. Audet ◽  
Carrie M. Quinn ◽  
Lisa R. Leon
Keyword(s):  
Cardiac Troponin ◽  
Point Of Care ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Field Tests ◽  
Organ Damage ◽  
Band Intensity ◽  
Health Concern ◽  
Clinical Test ◽  
Stroke Severity

Heat stroke (HS) remains a significant public health concern. Despite the substantial threat posed by HS, there is still no field or clinical test of HS severity. We suggested previously that circulating cardiac troponin (cTnI) could serve as a robust biomarker of HS severity after heating. In the present study, we hypothesized that (cTnI) point-of-care test (ctPOC) could be used to predict severity and organ damage at the onset of HS. Conscious male Fischer 344 rats ( n = 16) continuously monitored for heart rate (HR), blood pressure (BP), and core temperature (Tc) (radiotelemetry) were heated to maximum Tc (Tc,Max) of 41.9 ± 0.1°C and recovered undisturbed for 24 h at an ambient temperature of 20°C. Blood samples were taken at Tc,Max and 24 h after heat via submandibular bleed and analyzed on ctPOC test. POC cTnI band intensity was ranked using a simple four-point scale via two blinded observers and compared with cTnI levels measured by a clinical blood analyzer. Blood was also analyzed for biomarkers of systemic organ damage. HS severity, as previously defined using HR, BP, and recovery Tc profile during heat exposure, correlated strongly with cTnI ( R2 = 0.69) at Tc,Max. POC cTnI band intensity ranking accurately predicted cTnI levels ( R2 = 0.64) and HS severity ( R2 = 0.83). Five markers of systemic organ damage also correlated with ctPOC score (albumin, alanine aminotransferase, blood urea nitrogen, cholesterol, and total bilirubin; R2 > 0.4). This suggests that cTnI POC tests can accurately determine HS severity and could serve as simple, portable, cost-effective HS field tests.

scholarly journals Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model

2019 ◽  
Author(s):  
Elizabeth A. Proctor ◽  
Shauna M. Dineen ◽  
Stephen C. Van Nostrand ◽  
Madison K. Kuhn ◽  
Christopher D. Barrett ◽  
...  
Keyword(s):  
Body Temperature ◽  
Mouse Model ◽  
Core Body Temperature ◽  
Heat Stroke ◽  
Organ Damage ◽  
Supervised Machine Learning ◽  
Stroke Severity ◽  
Immune Challenge ◽  
Core Body ◽  
D Dimer

AbstractHeat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.Key pointsA signature of pro-coagulation markers predicts circadian core body temperature and levels of organ damage in heat strokeChanges in coagulopathy-related gene expression are evidenced before histopathological organ damage

scholarly journals NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zi-Teng Zhang ◽  
Xiao-Lei Gu ◽  
Xin Zhao ◽  
Xian He ◽  
Hao-Wei Shi ◽  
...  
Keyword(s):  
Heat Tolerance ◽  
Knockout Mice ◽  
Nlrp3 Inflammasome ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Neutralizing Antibody ◽  
Underlying Mechanism ◽  
Stroke Severity ◽  
Inflammasome Activation ◽  
Prior Infection

Abstract Background Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. Methods In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1β neutralizing antibody was injected to test potential therapeutic effect on heat stroke. Results Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1β in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1β production with prior infection condition. Furthermore, IL-1β neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. Conclusions Based on the above results, NLRP3/IL-1β induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1β may serve as a biomarker for heat stroke severity and potential therapeutic method.

scholarly journals Protective Effects of Salidroside on Mitochondrial Functions against Exertional Heat Stroke-Induced Organ Damage in the Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wei Zhang ◽  
Ming Peng ◽  
Yang Yang ◽  
Zhangwu Xiao ◽  
Bin Song ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Organ Damage ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Protective Effects ◽  
Exertional Heat Stroke ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Functions

Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. The present study was designed to evaluate the protective effects of salidroside on EHS by improving mitochondrial functions in the rat model. Liver and heart mitochondria were observed by transmission electron microscopy and mitochondrial membrane potential (ΔΨm) was detected by a fluorescent probe. Intramitochondrial free Ca2+concentration, mitochondrial respiratory control ratio (RCR), reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and malondialdehyde (MDA) activity were detected by the corresponding kits. RT-PCR was performed to estimate peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α) and manganese form of SOD (MnSOD) mRNA expression. The results demonstrated that salidroside was able to relieve EHS damage by reducing the swelling of mitochondria, ROS levels, and MDA activity, as well as increasing ΔΨm, RCR, free Ca2+concentration, SOD, PGC-1α, and MnSOD mRNA levels. In conclusion, salidroside has protective effects on mitochondrial functions against exertional heat stroke-induced organ damage in the rat.

scholarly journals A Case of Exertional Heat Stroke Complicated by Hypoxic Hepatitis

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Bertram K. Woitok ◽  
Shawki Bahmad ◽  
Gregor Lindner
Keyword(s):  
Supportive Care ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Multiorgan Failure ◽  
Heat Stroke ◽  
Exertional Heat Stroke ◽  
Hypoxic Hepatitis ◽  
Threatening Condition ◽  
Life Threatening ◽  
Delayed Referral

Background.Exertional heat stroke is a life-threatening condition often complicated by multiorgan failure. We hereby present a case of a 25-year-old male presenting with syncope after a 10  km run in 28°C outside temperature who developed acute liver failure. Case Presentation. Initial temperature was found to be 41.1°C, and cooling measures were rapidly applied. He suffered from acute renal failure and rhabdomyolysis and proceeded to acute liver failure (ASAT 6100 U/l and ALAT 6561 U/l) due to hypoxic hepatitis on day 3. He did not meet criteria for emergency liver transplantation and recovered on supportive care. Conclusions. Acute liver failure due to heat stroke is a life-threatening condition with often delayed onset, which nevertheless resolves on supportive care in the majority of cases; thus, a delayed referral to transplant seems to be reasonable.

scholarly journals A novel mouse model of heatstroke accounting for ambient temperature and relative humidity

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Kazuyuki Miyamoto ◽  
Keisuke Suzuki ◽  
Hirokazu Ohtaki ◽  
Motoyasu Nakamura ◽  
Hiroki Yamaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Temperature ◽  
Relative Humidity ◽  
Ambient Temperature ◽  
Core Body Temperature ◽  
Heat Exposure ◽  
Organ Damage ◽  
Core Body ◽  
The Impact ◽  
Treatment Water

Abstract Background Heatstroke is associated with exposure to high ambient temperature (AT) and relative humidity (RH), and an increased risk of organ damage or death. Previously proposed animal models of heatstroke disregard the impact of RH. Therefore, we aimed to establish and validate an animal model of heatstroke considering RH. To validate our model, we also examined the effect of hydration and investigated gene expression of cotransporter proteins in the intestinal membranes after heat exposure. Methods Mildly dehydrated adult male C57/BL6J mice were subjected to three AT conditions (37 °C, 41 °C, or 43 °C) at RH > 99% and monitored with WetBulb globe temperature (WBGT) for 1 h. The survival rate, body weight, core body temperature, blood parameters, and histologically confirmed tissue damage were evaluated to establish a mouse heatstroke model. Then, the mice received no treatment, water, or oral rehydration solution (ORS) before and after heat exposure; subsequent organ damage was compared using our model. Thereafter, we investigated cotransporter protein gene expressions in the intestinal membranes of mice that received no treatment, water, or ORS. Results The survival rates of mice exposed to ATs of 37 °C, 41 °C, and 43 °C were 100%, 83.3%, and 0%, respectively. From this result, we excluded AT43. Mice in the AT 41 °C group appeared to be more dehydrated than those in the AT 37 °C group. WBGT in the AT 41 °C group was > 44 °C; core body temperature in this group reached 41.3 ± 0.08 °C during heat exposure and decreased to 34.0 ± 0.18 °C, returning to baseline after 8 h which showed a biphasic thermal dysregulation response. The AT 41 °C group presented with greater hepatic, renal, and musculoskeletal damage than did the other groups. The impact of ORS on recovery was greater than that of water or no treatment. The administration of ORS with heat exposure increased cotransporter gene expression in the intestines and reduced heatstroke-related damage. Conclusions We developed a novel mouse heatstroke model that considered AT and RH. We found that ORS administration improved inadequate circulation and reduced tissue injury by increasing cotransporter gene expression in the intestines.

Assessing the Performance of a Novel Point-of-Care Qualitative Assay for Early Diagnosis of Acute Coronary Syndrome

Cardiology ◽  
2020 ◽  
pp. 1-8
Author(s):  
Ronny Alcalai ◽  
Boris Varshisky ◽  
Ahmad Marhig ◽  
David Leibowitz ◽  
Larissa Kogan-Boguslavsky ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Chest Pain ◽  
Diagnostic Accuracy ◽  
Diagnostic Performance ◽  
Troponin I ◽  
Point Of Care ◽  
Final Diagnosis ◽  
Cardiac Biomarkers ◽  
Fatty Acid Binding ◽  
Coronary Syndrome

<b><i>Background:</i></b> Early and accurate diagnosis of acute coronary syndrome (ACS) is essential for initiating lifesaving interventions. In this article, the diagnostic performance of a novel point-of-care rapid assay (SensAheart<sup>©</sup>) is analyzed. This assay qualitatively determines the presence of 2 cardiac biomarkers troponin I and heart-type fatty acid-binding protein that are present soon after onset of myocardial injury. <b><i>Methods:</i></b> We conducted a prospective observational study of consecutive patients who presented to the emergency department with typical chest pain. Simultaneous high-sensitive cardiac troponin T (hs-cTnT) and SensAheart testing was performed upon hospital admission. Diagnostic accuracy was computed using SensAheart or hs-cTnT levels versus the final diagnosis defined as positive/negative. <b><i>Results:</i></b> Of 225 patients analyzed, a final diagnosis of ACS was established in 138 patients, 87 individuals diagnosed with nonischemic chest pain. In the overall population, as compared to hs-cTnT, the sensitivity of the initial SensAheart assay was significantly higher (80.4 vs. 63.8%, <i>p</i> = 0.002) whereas specificity was lower (78.6 vs. 95.4%, <i>p</i> = 0.036). The overall diagnostic accuracy of SensAheart assay was similar to the hs-cTnT (82.7% compared to 76.0%, <i>p</i> = 0.08). <b><i>Conclusions:</i></b> Upon first medical contact, the novel point-of-care rapid SensAheart assay shows a diagnostic performance similar to hs-cTnT. The combination of 2 cardiac biomarkers in the same kit allows for very early detection of myocardial damage. The SensAheart assay is a reliable and practical tool for ruling-in the diagnosis of ACS.

Exertional heat stroke in a young man with a documented rise in troponin I

2008 ◽  
Vol 25 (5) ◽  
pp. 283-284 ◽  
Author(s):  
R Whiticar ◽  
D Laba ◽  
S Smith
Keyword(s):  
Troponin I ◽  
Heat Stroke ◽  
Exertional Heat Stroke
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