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.

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.

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 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.

scholarly journals High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers

2019 ◽  
Vol 57 (5) ◽  
pp. 623-632 ◽  
Author(s):  
Paul O. Collinson ◽  
Amy K. Saenger ◽  
Fred S. Apple ◽  
Keyword(s):  
Cardiac Troponin ◽  
Task Force ◽  
Clinical Chemistry ◽  
Point Of Care ◽  
High Sensitivity ◽  
Laboratory Medicine ◽  
International Federation ◽  
Cardiac Biomarkers ◽  
Educational Materials ◽  
Extensive Information

AbstractThe International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) formed a Task Force on the Application of Cardiac Bio-markers (TF-CB) in 2008, re-designated in 2018 as a committee (C-CB), to produce educational materials on cardiac biomarkers. Established in June 2017, definitive tables covering the majority of high-sensitivity, contemporary and point-of-care (POC) cTn assays have been developed by the C-CB and are available on the IFCC website. These tables provide extensive information about assays’ analytical characteristics and encompass information on diagnostic discriminants, particularly the 99th percentiles, as provided by the manufacturers.

scholarly journals Alpha-Lipoic Acid Protects Cardiomyocytes against Heat Stroke-Induced Apoptosis and Inflammatory Responses Associated with the Induction of Hsp70 and Activation of Autophagy

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hsin-Hsueh Shen ◽  
Yu-Shiuan Tseng ◽  
Ni-Chun Kuo ◽  
Ching-Wen Kung ◽  
Sherif Amin ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Myocardial Injury ◽  
Inflammatory Responses ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Antioxidant Properties ◽  
Mitochondrial Enzymes ◽  
Protective Effects ◽  
Anion Formation ◽  
Anti Inflammatory

Heat stroke (HS) is a life-threatening illness and defined as when body temperature elevates above 40°C accompanied by the systemic inflammatory response syndrome that results in multiple organ dysfunctions. α-Lipoic acid (ALA) acts as a cofactor of mitochondrial enzymes and exerts anti-inflammatory and antioxidant properties in a variety of diseases. This study investigates the beneficial effects of ALA on myocardial injury and organ damage caused by experimental HS and further explores its underlying mechanism. Male Wistar rats were exposed to 42°C until their rectal core temperature reached 42.9°C and ALA was pretreared 40 or 80 mg/kg (i.v.) 1.5 h prior to heat exposure. Results showed that HS-induced lethality and hypothermia were significantly alleviated by ALA treatment that also improved plasma levels of CRE, LDH, and CPK and myocardial injury biomarkers myoglobin and troponin. In addition, ALA reduced cardiac superoxide anion formation and protein expression of cleaved caspase 3 caused by HS. Proinflammatory cytokine TNF-α and NF-κB pathways were significantly reduced by ALA treatment which may be associated with the upregulation of Hsp70. ALA significantly increased the Atg5-12 complex and LC3B II/LC3B I ratio, whereas the p62 and p-mTOR expression was attenuated in HS rats, indicating the activation of autophagy by ALA. In conclusion, ALA ameliorated the deleterious effects of HS by exerting antioxidative and anti-inflammatory capacities. Induction of Hsp70 and activation of autophagy contribute to the protective effects of ALA in HS-induced myocardial injury.

Predictive Value of The Combined Detection of Platelets, D-Dimer, and Procalcitonin On Severe Heat Stroke

2021 ◽  
Author(s):  
wang lei ◽  
jiang dai shan ◽  
zhang Yi ◽  
jia han yu ◽  
shen jun hua
Keyword(s):  
Body Temperature ◽  
Characteristic Curve ◽  
Heat Stroke ◽  
Area Under The Curve ◽  
General Information ◽  
The Body ◽  
Control Group ◽  
Clinical Test ◽  
Roc Curve Analysis ◽  
Combined Detection

Abstract BackgroundTo explore the clinical characteristics of patients with severe heat stroke, we explored the early sensitive indicators of heat stroke (HS) patients, with a view to early intervention for HS patients. MethodsFrom July 30, 2015 to October 5, 2020, 70 inpatients with severe heat stroke admitted to the Second Affiliated Hospital of Nantong University, Jiangsu Province were selected as the research objects. The general information and clinical test indicators of the patients were recorded, and all patients were assessed for acute physiology (APACH Ⅱ) upon admission. According to the severity of heatstroke, they were divided into three groups: control group (heat cramps and heat exhaustion), EHS, and CHS to compare the differences in indicators of each group. Further draw the receiver operating characteristic curve (ROC).Results1. According to the severity of heat stroke, 28 cases were divided into the control group, 24 cases in the EHS group, and 18 cases in the CHS group. The body temperature of the EHS group and the CHS group was significantly higher than that of the control group (both P<0.05), but there was no statistical difference in the body temperature of the EHS group and the CHS group; the DD, PCT, and APACH of the EHS group were significantly higher than those of the control group and the CHS group (both P＜0.05); PLT, CRP, Na, GLU of EHS group were lower than those of control group and CHS group (all P＜0.05), and the decrease of PLT was more significant; CHS group HbA1C was significantly higher than that of control group and EHS group (all P <0.05). 2. ROC curve analysis the areas under the curves of DD, PCT, and PLT are 0.670, 0.705, 0.791, respectively, the sensitivity is 40.48%, 100%, 73.81%, and the specificity is 96.43%, 32.14%, 78.57%, respectively. Using the combined analysis of the three series tests, the area under the curve was 0.838, the sensitivity was 71.43%, and the specificity was 85.71%. ConclusionsEHS patients have higher DD, PCT, APACH, but PLT, CRP, Na, and blood sugar are lower. At the same time, the significant decrease of PLT and the increase of PCT and DD may be early sensitive indicators of HS. The combined detection of the three can be used as a reference basis for early diagnosis of HS and critical illness.

Heat

2020 ◽  
pp. 1687-1689
Author(s):  
Michael A. Stroud
Keyword(s):  
Physical Activity ◽  
Body Temperature ◽  
Supportive Care ◽  
Physiological Responses ◽  
Heat Stroke ◽  
Heat Exposure ◽  
High Humidity ◽  
Heat Exhaustion ◽  
Clinical Presentations ◽  
Cold Core

Rising body temperature triggers behavioural and physiological responses including reduction in physical activity, alterations of clothing, skin vasodilatation, and sweating. Heat-related illness is relatively common, especially with high humidity or prolonged physical activity. Risk can be reduced by acclimatization with repeated heat exposure, but some individuals seem to be particularly susceptible. Clinical presentations of heat-related illness include (1) ‘heat exhaustion’—the commonest manifestation, with symptoms including nausea, weakness, headache, and thirst. Patients appear dehydrated, complain of being hot, and are flushed and sweaty. Treatment requires rest and fluids, given orally or (in severe cases) intravenously. (2) ‘Heat stroke’ victims often complain of headache, may be drowsy or irritable, and may claim to feel cold. Core temperature is usually 38–41°C, but the patient is shivering with dry, vasoconstricted skin. Treatment requires (a) aggressive rapid cooling; (b) close biochemical monitoring; (c) supportive care for organ failure. There is significant mortality.

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