Hypoxia-inducible factor prolyl hydroxylase inhibitor alleviates heatstroke-induced acute kidney injury by activating BNIP3-mediated mitophagy.

Hypoxia-induced inflammation and apoptosis are important pathophysiological features of heat stroke-induced acute kidney injury (HS-AKI). Hypoxia-inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF-PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF-PHI could alleviate HS-induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi-1, 3-MA, and Baf-A1 reversed the renoprotective effects of HIF-PHI. Mechanistically, HIF-PHI protects RTECs from inflammation and apoptosis by enhancing Bcl-2 adenovirus E18 19-kDa-interacting protein 3 (BNIP3)-mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF-PHI-induced mitophagy and abolished HIF-PHI-mediated renal protection. Thus, our results indicated that HIF-PHI protects renal function by upregulating BNIP3-mediated mitophagy to improve HS-induced inflammation and apoptosis of RTECs, suggesting HIF-PHI as a promising therapeutic agent to treat HS-AKI.

Biological sex impacts oxidative stress in skeletal muscle in a porcine heat stress model.

Oxidative stress contributes to heat stress (HS)-mediated alterations in skeletal muscle; however, the extent to which biological sex mediates oxidative stress during HS remains unknown. We hypothesized muscle from males would be more resistant to oxidative stress caused by HS than muscle from females. To address this, male and female pigs were housed in thermoneutral conditions (TN; 20.8 ± 1.6°C; 62.0 ± 4.7% relative humidity; n = 8/sex) or subjected to HS (39.4 ± 0.6°C; 33.7 ± 6.3% relative humidity) for 1 (HS1; n = 8/sex) or 7 days (HS7; n = 8/sex) followed by collection of the oxidative portion of the semitendinosus. Although HS increased muscle temperature, by 7 days, muscle from heat-stressed females was cooler than muscle from heat-stressed males (0.3°C; P < 0.05). Relative protein abundance of 4-hydroxynonenal (4-HNE)-modified proteins increased in HS1 females compared with TN (P = 0.05). Furthermore, malondialdehyde (MDA)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration, a DNA damage marker, was increased in HS7 females compared with TN females (P = 0.05). Enzymatic activities of catalase and superoxide dismutase (SOD) remained similar between groups; however, glutathione peroxidase (GPX) activity decreased in HS7 females compared with TN and HS1 females (P ≤ 0.03) and HS7 males (P = 0.02). Notably, HS increased skeletal muscle Ca2+ deposition (P = 0.05) and was greater in HS1 females compared with TN females (P < 0.05). Heat stress increased sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2a protein abundance (P < 0.01); however, Ca2+ ATPase activity remained similar between groups. Overall, despite having lower muscle temperature, muscle from heat-stressed females had increased markers of oxidative stress and calcium deposition than muscle from males following identical environmental exposure.NEW & NOTEWORTHY Heat stress is a global threat to human health and agricultural production. We demonstrated that following 7 days of heat stress, skeletal muscle from females was more susceptible to oxidative stress than muscle from males in a porcine model, despite cooler muscle temperatures. The vulnerability to heat stress-induced oxidative stress in females may be driven, at least in part, by decreased antioxidant capacity and calcium dysregulation.

Effects of sodium bicarbonate ingestion on ventilatory and cerebrovascular responses in resting heated humans.

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptors activity, mitigate hyperthermia-induced hyperventilation. We also assessed that the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested a sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (VE) during the heating were similar in the two trials. Moreover, when VE is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (37.9 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.338), and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-VE relation (13.7 ± 14.9 vs. 15.8 ± 15.6 L/min/°C, P = 0.748). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.

Exertional heat stroke-induced changes in gut microbiota cause cognitive impairment in mice.

BACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent. METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed. RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28. CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.

Regulation of body temperature and blood pressure in women: Mechanisms and implications for heat illness risk.

Increasing global temperatures due to ongoing climate change phenomena have resulted in increased risk of exertional heat illness in otherwise healthy, young individuals who work or play in the heat. With increasing participation of women in athletic, military and industrial activities that involve exertion in the heat, there is a growing need to study female physiology in this context. Mechanisms controlling blood pressure and body temperature have substantial overlap in humans, largely due to autonomic mechanisms which contribute to both. Similarly, illnesses that result from excessive heat exposure can often be traced back to imbalances in one or more of these autonomic mechanisms. In recent years, there has been increased recognition of the importance of sex as a biological variable for basic and applied research in these areas. The goal of this paper is to present an update on the integrative physiology and pathophysiology of responses to heat stress in women (thermoregulation and blood pressure regulation). In this context, it is often the case that differences between sexes are presented as 'advantages' and 'disadvantages' of one sex over the other. In our opinion, this is an over-simplification of the physiology which ignores the nuances and complexities of the integrative physiology of responses to heat exposure and exercise, and their relevance for practical outcomes.

Ingesting carbonated water post-exercise in the heat transiently ameliorates hypotension and enhances mood state.

The objective was to assess if post-exercise ingestion of carbonated water in a hot environment ameliorates hypotension, enhances cerebral blood flow and heat loss responses, and positively modulates perceptions and mood states. Twelve healthy, habitually active young adults (five women) performed 60 min of cycling at 45% peak oxygen uptake in a hot climate (35°C). Subsequently, participants consumed 4°C carbonated or non-carbonated (control) water (150 and 100 mL for males and females regardless of drink type) at 20 and 40 min into post-exercise periods. Mean arterial pressure decreased post-exercise at 20 min only (P = 0.032) compared to the pre-exercise baseline. Both beverages transiently (∼1 min) increased mean arterial pressure and middle cerebral artery mean blood velocity (cerebral blood flow index) regardless of post-exercise periods (all P ≤ 0.015). Notably, carbonated water ingestion led to greater increases in mean arterial pressure (2.3 ± 2.8 mmHg vs. 6.6 ± 4.4 mmHg, P < 0.001) and middle cerebral artery mean blood velocity (1.6 ± 2.5 cm/s vs. 3.8 ± 4.1 cm/s, P = 0.046) at 20 min post-exercise period compared to non-carbonated water ingestion. Both beverages increased mouth exhilaration and reduced sleepiness regardless of post-exercise periods, but these responses were more pronounced with carbonated water ingestion at 40 min post-exercise (mouth exhilaration: 3.1 ± 1.4 vs. 4.7 ± 1.7, P = 0.001; sleepiness: -0.7 ± 0.91 vs. -1.9 ± 1.6, P = 0.014). Heat loss responses and other perceptions were similar between the two conditions throughout (all P ≥ 0.054). We show that carbonated water ingestion temporarily ameliorates hypotension and increases the cerebral blood flow index during the early post-exercise phase in a hot environment, whereas it enhances mouth exhilaration and reduces sleepiness during the late post-exercise phase.

"Unravelling the impacts of climatic heat events on cardiovascular health in animal models".

Climate change has led to an increase in high ambient temperatures, causing extreme heat events worldwide. According to the World Meteorological Organization (WMO), July 2023 marked a historic milestone as the Earth reached its hottest recorded temperature, precisely hitting the critical threshold of 1.5 °C set by the Paris Agreement. This distressing development led to a stark warning from the United Nations, signaling the dawn of what they call "an era of global boiling". The increasing global temperatures can result in high heat stress which leads to various physiological and biochemical alterations in the human body. Given that cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally, heat events exacerbate this public health issue. While clinical and in-vitro studies have suggested a range of pathophysiological and biochemical mechanisms underlying the body's response to heat stress, the complex nature of organ-system level interactions makes precise investigation challenging. To address this knowledge gap effectively, the use of animal models exposed to acute or chronic heat stress can be invaluable. These models can closely replicate the multifaceted effects observed in humans during heat stress conditions. Despite extensive independent reviews, limited focus has been shed on the high heat-induced cardiovascular complications and their mechanisms, particularly utilizing animal models. Therefore, in this comprehensive review, we highlight the crucial biomarkers altered during heat stress, contributing significantly to various CVDs. We explore potential mechanisms underlying heat-induced cardiovascular dysfunction and damage, delving into various animal models. While traditional rodent models are commonly employed, we also examine less conventional models, including ruminants, broilers, canines, and primates. Furthermore, we delve into various potential therapeutic approaches and preventive measures. These insights hold significant promise for the development of more effective clinical interventions against the effects of heat stress on the human cardiovascular system.

Impact of heat waves on human morbidity and hospital admissions in a city of the western mediterranean area.

PURPOSE: The effect of heat waves on mortality is well known, but current evidence on morbidity is limited. Establishing the consequences of these events in terms of morbidity is important to ensure communities and health systems can adapt to them. METHODS: We thus collected data on total daily emergency hospital admissions, admissions to critical care units, emergency department admissions, and emergency admissions for specific diagnoses to Hospital Universitario de Son Espases from 1 January 2005 to 31 December 2021. A heat wave was defined as a period of ≥ 2 days with a maximum temperature ≥ 35 °C, including a 7 day lag effect (inclusive). We used a quasi-Poisson generalized linear model to estimate relative risks (RRs; 95%CI) for heat wave-related hospital admissions. RESULTS: Results showed statistically significant increases in total emergency admissions (RR 1.06; 95%CI 1 - 1.12), emergency department admissions (RR 1.12; 95%CI 1.07 - 1.18), and admissions for ischemic stroke (RR 1.26; 95%CI 1.02 - 1.54), acute kidney injury (RR 1.67; 95%CI 1.16 - 2.35), and heat stroke (RR 18.73, 95%CI 6.48 - 45.83) during heat waves. CONCLUSION: Heat waves increase hospitalization risk, primarily for thromboembolic and renal diseases and heat strokes.

Quantitative Proteomics Provided Insights into the Protective Effects of Heat Acclimation on the Rat Hypothalamus after Exertional Heatstroke.

BACKGROUND: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. METHODS: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. RESULTS: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1ß, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. CONCLUSIONS: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.

Mesenchymal stem cell-derived exosomal miR-548x-3p inhibits pyroptosis of vascular endothelial cells through HMGB1 in heat stroke.

Heat stroke (HS) is an acute physical illness associated with a higher risk of organ dysfunction. This study is the first to explore exosomal miR-548x-3p derived from human bone marrow mesenchymal stem cells (BMSCs) in the pyroptosis of vascular endothelial cells (VECs) associated with HS. Human BMSCs-derived exosome alleviated the injury of the heart, liver, kidney and ileum tissues, the increase of IL-1ß, IL-18 and TNF-α levels, pyroptosis of endothelial cells and the increase of HGMB1, NLRP3, ASC, caspase1 and GSDMD-N protein expression in HS mice and HS-induced human umbilical vein endothelial cells (HUVECs). miR-548x-3p was down-expressed in HS patients, while up-expressed in BMSCs-derived exosome. BMSCs-ExomiR-548x-3p mimics to inhibit pyroptosis, inflammation and HGMB1/NLRP3 activation in HS-induced HUVECs and HS mice, which were blocked by overexpression of HMGB1. In conclusion, human BMSCs-derived exosomes carried miR-548x-3p mimics to inhibit pyroptosis of VECs through HMGB1 in HS mice.

Association between normal saline infusion volume in the emergency department and acute kidney injury in heat stroke patients: a multicenter retrospective study.

BACKGROUND: Previous studies have shown that intravenous normal saline (NS) may be associated with the incidence of acute kidney injury (AKI). This study aimed to evaluate the association between the volume of NS infusion and AKI in heat stroke (HS) patients. METHODS: This multicenter retrospective cohort study included 138 patients with HS. The primary outcome was the incidence of AKI. Secondary outcomes included the need for continuous renal replacement therapy (CRRT), admission to the intensive care unit (ICU), length of stay in the ICU and hospital, and in-hospital mortality. Multivariate regression models, random forest imputation, and genetic and propensity score matching were used to explore the relationship between NS infusion and outcomes. RESULTS: The mean volume of NS infusion in the emergency department (ED) was 3.02 ± 1.45 L. During hospitalization, 33 patients (23.91%) suffered from AKI. In the multivariate model, as a continuous variable (per 1 L), the volume of NS infusion was associated with the incidence of AKI (OR, 2.51; 95% CI, 1.43-4.40; p = .001), admission to the ICU (OR, 3.46; 95% CI 1.58-7.54; p = .002), and length of stay in the ICU (ß, 1.00 days; 95% CI, 0.44-1.56; p < .001) and hospital (ß, 1.41 days; 95% CI, 0.37-2.45; p = .008). These relationships also existed in the forest imputation cohort and matching cohort. There were no differences in the use of CRRT or in-hospital mortality. CONCLUSIONS: The volume of NS infusion was associated with a significant increase in the incidence of AKI, admission to the ICU, and length of stay in the ICU and hospital among patients with HS.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2024 Update.

The Wilderness Medical Society (WMS) convened an expert panel in 2011 to develop a set of evidence-based guidelines for the recognition, prevention, and treatment of heat illness. The current panel retained 5 original members and welcomed 2 new members, all of whom collaborated remotely to provide an updated review of the classifications, pathophysiology, evidence-based guidelines for planning and preventive measures, and recommendations for field- and hospital-based therapeutic management of heat illness. These recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks or burdens for each modality. This is an updated version of the WMS clinical practice guidelines for the prevention and treatment of heat illness published in Wilderness & Environmental Medicine. 2019;30(4):S33-S46.

Case discussion: The effect of extreme temperatures on an older adult.

Climate change can cause high temperatures that can affect the older adult in significant ways. Older adults may not be aware of the dangers of high temperature days and may continue with old habits such as staying in the sun to garden without sunscreen or a hat as they may have done in years past. High temperatures can cause impairment of the tone and structure of blood vessels by interfering with nitric oxide synthesis and cytokine production and can cause systemic inflammation, all of which significantly contribute to dehydration in older adults, who are known to have a decreased sense of thirst, resulting in increased blood viscosity and the risk of heat induced shock and thrombotic strokes. This case discussion highlights the effects of high temperatures due to climate change on an older adult, and what nurse practitioners need to be aware of when assessing older adults who may be suffering from heat exhaustion or heat stroke, and how to manage appropriately.

[Constructing an early-warning model for mortality risk in heat stroke patients based on Fisher discriminant analysis].

Objective: To establish an early warning model to assess the mortality risk of patients with heat stroke disease. Methods: The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model. Results: The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%. Conclusion: The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

Whole genome transcriptomic reveals heat stroke molecular signatures in humans.

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7 ± 0.8°C, and eight were in deep coma (Glasgow Coma Score = 3). The transcriptome showed that genes involved in more than half of the entire chaperome were differentially expressed relative to heat stress control. These include the heat shock protein, cochaperone, and chaperonin genes, indicating a robust HSR. Differentially expressed genes also encoded proteins related to unfolded protein response, DNA repair, energy metabolism, oxidative stress, and immunity. The analysis predicted perturbations of the proteome network and energy production. Cooling therapy attenuated these alterations without complete restoration of homeostasis. We validated the significantly expressed genes by a real-time polymerase chain reaction. The findings reveal the molecular signature of heat stroke. They also suggested that a powerful HSR may not be sufficient to protect against heat injury. The overwhelming proteotoxicity and energy failure could play a pathogenic role. KEY POINTS: Most living species, including humans, have inherent heat stress response (HSR) that shields them against heat-induced macromolecular damage. The role of the HSR in subjects exposed to environmental heat who progressed to heat stroke versus those that did not is unknown. Our findings suggest that heat stroke induces a broad and robust HSR of nearly half of the total heat shock proteins, cochaperones, and chaperonin genes. Heat stroke patients exhibited inhibition of genes involved in energy production, including oxidative phosphorylation and ATP production. Significant enrichment of neurodegenerative pathways, including amyloid processing signalling, the Huntington's and Parkinson's disease signalling suggestive of brain proteotoxicity was noted. The data suggests that more than a powerful HSR may be required to protect against heat stroke. Overwhelming proteotoxicity and energy failure might contribute to its pathogenesis.

Classic heat stroke in a desert climate: A systematic review of 2632 cases.

BACKGROUND: Although classic heat stroke (HS) is one of the most ancient conditions known to humans, the description of its early clinical manifestations, natural course, and complications remains uncertain. OBJECTIVES: A systematic review of the demographics, clinical characteristics, biomarkers, therapy, and outcomes of HS during the Muslim (Hajj) pilgrimage in the desert climate of Mecca, Saudi Arabia. METHODS: We searched the MEDLINE, Embase, Web of Science Core Collection, SCOPUS, and CINAHL databases from inception to April 2022. We summarized the data from eligible studies and synthesized them in narrative form using pooled descriptive statistics. RESULTS: Forty-four studies, including 2632 patients with HS, met the inclusion criteria. Overweight or obesity, diabetes, and cardiovascular disease were prevalent among cases of HS. Evidence suggests that extreme hyperthermia (pooled mean = 42.0°C [95% confidence interval (CI): 41.9, 42.1], range 40-44.8°C) with hot and dry skin (>99% of cases) and severe loss of consciousness (mean Glasgow Coma Scale <8 in 53.8% of cases) were the dominant clinical characteristics of classic HS. Hypotension, tachypnea, vomiting, diarrhea, and biochemical biomarkers indicating mild-to-moderate rhabdomyolysis, acute kidney, liver, heart injury, and coagulopathy were frequent at the onset. Concomitantly, stress hormones (cortisol and catecholamines) and biomarkers of systemic inflammation and coagulation activation were increased. HS was fatal in 1 in 18 cases (pooled case fatality rate = 5.6% [95%CI: 4.6, 6.5]). CONCLUSIONS: The findings of this review suggest that HS induces an early multiorgan injury that can progress rapidly to organ failure, culminating in death, if it is not recognized and treated promptly.

Climate change and nephrology.

Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.

Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

OBJECTIVES: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). METHODS: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. RESULTS: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042). CONCLUSIONS: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. CLINICAL RELEVANCE STATEMENT: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. KEY POINTS: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

Whole-body cooling effectiveness of cold intravenous saline following exercise hyperthermia: a randomized trial.

INTRODUCTION: In some athletic, occupational, military and emergency settings, cold intravenous (IV) fluids are used to facilitate whole-body cooling in an effort to treat heat illness. This treatment has anecdotal support, but currently lacks evidence supporting it as a whole-body cooling modality. Other modalities may offer superior cooling rates, and thus, patient outcomes following treatment. We sought to evaluate cooling rates of cold-IV normal saline immediately following exercise-induced hyperthermia. METHODS: Eight healthy participants (3 females; 25 ± 2y; 72.9 ± 10.9 kg) completed 2 trials in random order. Prior to exercise, participants provided a small urine sample to confirm hydration status via urine specific gravity. Wet bulb globe temperature (WBGT) was assessed throughout trials. In both trials, participants exercised outdoors until rectal temperature (Tre) reached ∼38.9 °C, or volitional exhaustion, and then were cooled. In cooling, participants received either cold-IV (∼5 °C 0.9% NaCl fluids) or no treatment (sat in the shade; passive). Throughout exercise and treatment, Tre and heart rate (HR) were monitored. During exercise and every 10 min throughout cooling, participants were asked to assess thermal sensation. RESULTS: Hydration status (P = .847) was not significantly different prior to exercise between trials. WBGT throughout was not different between trials (P = .426). Maximum Tre reached was not different between cold-IV (38.88 ± 0.30 °C) and passive cooling (38.76 ± 0.28 °C) trials (P = .184). Mean cooling rate for cold-IV (0.039 ± 0.005 °C·min-1) was significantly greater than for passive cooling (0.028 ± 0.005 °C·min-1; P = .002). Tre throughout cooling was not different between trials (P = .707), but did decrease throughout (P = .008), regardless of trial. HR was decreased over time (P < .001), but cold-IV and passive cooling were not different throughout HR recovery (P = .141). Thermal sensation decreased throughout cooling (P < .001), but was not different between trials (p = .278). CONCLUSION: Emergency medical personnel should adopt treatment protocols that employ documented effective treatments for exertional heat stroke. In isolation, our data casts significant doubt for the use of cold-IV saline infusion for whole-body cooling of hyperthermic individuals.

The association of standard base excess upon emergency admission with outcomes in patients with heat stroke.

OBJECTIVES: Standard base excess (SBE) is a quick and effective tool to identify acid-base disorders in critically ill patients, independent of respiratory factors. The predictive value of SBE for adverse outcomes in patients with heat stroke (HS) is still unclear. This study aimed to explore the prognostic significance of SBE for in-hospital mortality and other adverse outcomes in patients with HS. METHODS: A retrospective, observational multicenter cohort study with consecutive patients between 2021 and 2022 was conducted. The SBE was performed upon emergency department (ED) admission. The primary outcome was in-hospital mortality. Secondary outcomes included the use of vasoactive drugs in the ED, admission to the ICU, acute kidney failure, acute heart failure, acute respiratory failure, sepsis, and coagulation impairment. Logistic regression models and receiver operating characteristic (ROC) curves were used to estimate the association of SBE with outcomes in HS patients. Interaction and stratified analyses were also conducted. RESULTS: The median level of SBE was -4.70 (-8.05- -1.55) mmol/L. Overall hospital mortality in these 151 HS patients was 12.58%. SBE was independently associated with hospital mortality (OR 0.81, 95% CI 0.70-0.95, P = 0.011). Age and HS type played interactive roles in the relationship between SBE and in-hospital mortality. The OR between SBE and hospital mortality was 0.5 (95% CI, 0.3-0.9; p < 0.018) in classic HS participants and 0.62 (95% CI, 0.45-0.87; p = 0.005) in participants aged >65 years. The AUC of SBE to predict in-hospital mortality was 0.868 (95% CI: 0.704-0.962) and 0.883 (95% CI: 0.750-0.951) in these two groups, respectively. SBE was significantly associated with admission to the ICU, acute kidney failure, acute respiratory failure, sepsis, and coagulation impairment. CONCLUSION: SBE upon emergency admission was significantly associated with adverse outcomes in patients with HS.