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

Audet, Gerald N.; Quinn, Carrie M.; Leon, Lisa R.

doi:10.1152/ajpregu.00286.2015

Cited by 11 publications

(9 citation statements)

References 62 publications

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“…Emerging evidence supports the value of Ang II and Ang-(1-7) as potential biomarkers, mainly in inflammatory diseases [19, 20]. In addition, considering that liver damage is always delayed by a few days, there are few reliable markers to predict the occurrence and prognosis of liver damage as a result of heatstroke [21, 22]. In this study, we first found that the reversed ratio of Ang II and Ang-(1-7) was associated with hepatic damage and illness severity in heatstroke patients.…”

Section: Discussionmentioning

confidence: 99%

AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway

Zhang

Zhu

Tong

et al. 2019

BioMed Research International

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We previously demonstrated that angiotensin-(1-7) (Ang-(1-7)), an essential endocrine factor, inhibits the NLRP3 inflammasome by regulating reactive oxygen species (ROS) in fibrotic livers. We also demonstrated that the NLRP3 inflammasome contributes to the liver damage induced by pyroptosis after heatstroke. However, the role of Ang-(1-7) in the hepatocytes under heat stress remains uncertain. We aimed to examine the change in angiotensin peptides in the livers affected by heatstroke and the effect on the ROS-NLRP3 inflammatory signalling pathway. In vivo, increased angiotensin II (Ang II) and decreased Ang-(1-7) in the serum of heatstroke patients suffering from hepatic dysfunction were observed. The change in angiotensin peptides was considered a potential biomarker that could be used to predict hepatic dysfunction. Enhanced Ang II and attenuated Ang-(1-7) levels were also observed in the liver tissue of heatstroke rats, which were consistent with their receptors and converting enzymes. Hepatic damage associated with increased ROS and protein expression levels of NOX4, NLRP3, caspase-1, and IL-1β was attenuated by AVE 0991, an analogue of Ang-(1-7). In vitro, pyroptosis, characterized by activated caspase-1 and IL-1β, was observed in hepatocytes under heat stress, which was enhanced by Ang II and attenuated by antioxidants, NOX4 siRNA, and AVE 0991. In summary, AVE 0991 attenuates pyroptosis and liver damage induced by heat stress by inhibiting the ROS-NLRP3 inflammatory signalling pathway.

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Section: Discussionmentioning

confidence: 99%

AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway

Zhang

Zhu

Tong

et al. 2019

BioMed Research International

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“…Several extra-cardiac mechanisms were proposed as contributing processes to myocardial damage and development of cardiac arrhythmias in heatstroke, in both humans and animals, including myocardial hypoperfusion and injury, lactic acidosis, hypoxemia, electrolyte imbalance and possibly, direct thermal injury. [87][88][89] Serum cardiac troponins I and T concentrations are increased in naturally occurring exertional and environmental heatstroke in both human patients and dogs, as well as in rats induced with heatstroke. 63,87,90,91 In the latter, cardiac troponin concentration accurately predicted the severity of the heatstroke.…”

Section: Myocardial Damage and Cardiac Arrhythmiamentioning

confidence: 99%

“…[87][88][89] Serum cardiac troponins I and T concentrations are increased in naturally occurring exertional and environmental heatstroke in both human patients and dogs, as well as in rats induced with heatstroke. 63,87,90,91 In the latter, cardiac troponin concentration accurately predicted the severity of the heatstroke. 87 Necropsy findings in dogs with fatal naturally occurring heatstroke invariably showed mild to severe subendocardial, myocardial and epicardial hemorrhages and hyperemia, 58 suggesting that DIC has a pivotal role in the pathogenesis of heatstrokeassociated cardiac arrhythmias.…”

Section: Myocardial Damage and Cardiac Arrhythmiamentioning

confidence: 99%

Pathophysiology of heatstroke in dogs – revisited

2017

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Heatstroke results from a failure to dissipate accumulated heat during exposure to hot environments, or during strenuous physical exercise under heat stress. It is characterized by core body temperatures > 41°C, with central nervous system dysfunction. Functional morphology and thermoregulatory effectors differences between dogs and humans may require special heatstroke protective adaptations in dogs, however, the risk factors for developing heatstroke are similar in both. In dogs, these include hot, especially highly humid environments, excessive physical activity, obesity, large (>15 kg) body weight, being of certain breed (e.g., Labrador retrievers and brachycephalic breeds), upper airway obstruction and prolonged seizures. Lack of acclimation to heat and physical fitness decreases the survival of heat stroked dogs. At the systemic level, blood pooling within the large internal organs (e.g., spleen, liver) is a major contributor to the development of shock and consequent intestinal ischemia, hypoxia and endothelial hyperpermeability, commonly occurring in heatstroke patients. Evoked serious complications include rhabdomyolysis, acute kidney injury, acute respiratory distress syndrome and ultimately, sepsis and disseminated intravascular coagulation. The most common clinical signs in dogs include acute collapse, tachypnea, spontaneous bleeding, shock signs and mental abnormalities, including depression, disorientation or delirium, seizures, stupor and coma. In such dogs, presence of peripheral blood nucleated red blood cells uniquely occurs, and is a highly sensitive diagnostic and prognostic biomarker. Despite early, appropriate body cooling, and intensive supportive treatment, with no available specific treatment to ameliorate the severe inflammatory and hemostatic derangements, the mortality rate is around 50%, similar to that of human heatstroke victims. This review discusses the pathophysiology of canine heatstroke from a veterinarian's point of view, integrating new and old studies and knowledge.

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“…While we did not measure responses at hypothermic depth in the SEV rats, our data at 1D and T c,Max in conjunction with previous mouse studies suggest that increased hypothalamic chemokine/cytokine expression is linked to the recovery T c profile, and could be driving hypothermia in a yet undetermined manor. The key point separating our two rodent models is that hypothermia during recovery in mice is considered a regulated response and necessary for recovery [7,34,39], while it is a marker of severity in rats [6,40]. However, we have previously shown in our mouse model that the greatest alterations in gene expression of the brain (and systemically) occur at hypothermia depth [12].…”

mentioning

confidence: 99%

Altered hypothalamic inflammatory gene expression correlates with heat stroke severity in a conscious rodent model

et al. 2016

Self Cite

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It has been suggested that heat-induced hypothalamic damage mediates core temperature (Tc) disturbances during heat stroke (HS) recovery; this is significant as hypothermia and/or fever have been linked to severity and overall pathological insult. However, to date there has been a lack of histological evidence in support of these claims. We hypothesized that local hypothalamic cytokines and/or chemokines, known regulators of Tc, are mediating the elevation in Tc during HS recovery even in the absence of histological damage. In experiment 1, the hypothalamus of Fischer 344 rats was examined for 84 cytokine/chemokine genes (real-time PCR) at multiple time points (Tc,Max, 1, 3, and 10 days) during mild HS recovery. In experiment 2, the hypothalamus of three different HS severities (MILD, moderate [MOD], and severe [SEV]) in rats were examined for the same genes as experiment 1 as well as six oxidative damage markers, at a single intermediate time point (1 day). Systemic cytokines were also analyzed in experiment 2 across the three severities. There were significant alterations in 25 cytokines/chemokines expression at Tc,Max, but little or no changes in expression at longer time points in experiment 1. In experiment 2 there were significant changes in gene expression in SEV rats only, with MILD and MOD rats showing baseline expression at 1 day, despite an absence of systemic cytokine expression in any severity. There was also no change in any oxidative marker of damage at 1 day, regardless of severity. In conclusion, we show only limited changes during long term recovery from HS, but demonstrate differences in hypothalamic gene expression patterns that may be driving HS pathology and morbidity. These findings contribute to our overall understanding of HS pathology in the CNS, as well as providing avenues for future pharmacological intervention.

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

Cited by 11 publications

References 62 publications

AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway

AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway

Pathophysiology of heatstroke in dogs – revisited

Altered hypothalamic inflammatory gene expression correlates with heat stroke severity in a conscious rodent model

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