Vancomycin modestly attenuates symptom severity during onset of and recovery from exertional heat stroke in mice.

Increased intestinal permeability during exertion and subsequent leakage of bacteria into circulation is hypothesized to accelerate exertional heat stroke (EHS) onset and/or exacerbate EHS severity. To provide proof of concept for this theory, we targeted intestinal microbiota via antibiotic prophylaxis and determined whether vancomycin would delay EHS onset and/or mitigate EHS severity and mortality rates using a mouse model of EHS. Mice were ) designated as EHS or Exercise Control (ExC) and ) given 7 days of vancomycin (VEHS, VExC) or untreated water (EHS, ExC) before EHS/Exercise.

Ovariectomy aggravates the pathophysiological response to exertional heat stroke in mice.

Female mice have a greater capacity for exercising in the heat than male mice, reaching greater power output and longer times of heat exposure before succumbing to exertional heat stroke (EHS). Differences in body mass, size, or testosterone do not explain these distinct sex responses. Whether the ovaries could account for the superior exercise capacity in the heat in females remains unknown.

Exertional heat stroke: pathophysiology and risk factors.

Exertional heat stroke, the third leading cause of mortality in athletes during physical activity, is the most severe manifestation of exertional heat illnesses. Exertional heat stroke is characterised by central nervous system dysfunction in people with hyperthermia during physical activity and can be influenced by environmental factors such as heatwaves, which extend the incidence of exertional heat stroke beyond athletics only. Epidemiological data indicate mortality rates of about 27%, and survivors display long term negative health consequences ranging from neurological to cardiovascular dysfunction.

Identification of therapeutic targets in a murine model of severe exertional heat stroke.

Exertional heat stroke (EHS) is a potentially lethal condition resulting from high core body temperatures (T) in combination with a systemic inflammatory response syndrome (SIRS) with varying degrees of severity across victims, and limited understanding of the underlying mechanism(s). We established a mouse model of severe EHS to identify mechanisms of hyperthermia/inflammation that may be responsible for organ damage. Mice were forced to run on a motorized wheel in a 37.

Drug-Induced Hyperthermia Review.

Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs.

Classic and exertional heatstroke.

In the past two decades, record-breaking heatwaves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a heat illness characterized by the rapid rise of core body temperature above 40 °C and central nervous system dysfunction. It is categorized as classic when it results from passive exposure to extreme environmental heat and as exertional when it develops during strenuous exercise.

Impact of successive exertional heat injuries on thermoregulatory and systemic inflammatory responses in mice.

The purpose of the study was to determine if repeated exertional heat injuries (EHIs) worsen the inflammatory response. We assessed the impact of a single EHI bout (EHI0) or two separate EHI episodes separated by 1 (EHI1), 3 (EHI3), and 7 (EHI7) days in male C57BL/6J mice ( = 236). To induce EHI, mice underwent a forced running protocol until loss of consciousness or core temperature reached ≥ 42.

The Role of Skeletal Muscles in Exertional Heat Stroke Pathophysiology.

The active participation of skeletal muscles is a unique characteristic of exertional heat stroke. Nevertheless, the only well-documented link between skeletal muscle activities and exertional heat stroke pathophysiology is the extensive muscle damage (e. g.

Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture.

Exertional heat stroke (EHS) and malignant hyperthermia (MH) are life-threatening conditions, triggered by different environmental stimuli that share several clinical symptoms and pathophysiological features. EHS manifests during physical activity normally, but not always, in hot and humid environments. MH manifests during exposure to haloalkane anesthetics or succinylcholine, which leads to a rapid, unregulated release of calcium (Ca) within the skeletal muscles inducing a positive-feedback loop within the excitation-contraction coupling mechanism that culminates in heat stroke-like symptoms, if not rapidly recognized and treated.

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

Background: Immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear.

Objectives: We sought to understand the effect of immune challenge on heat stroke pathology.

Patients/methods: Using a mouse model of classic heat stroke, we examined the impact of prior viral or bacterial infection on hematological aspects of recovery.

Prior viral illness increases heat stroke severity in mice.

New Findings: What is the central question of this study? We hypothesized that prior illness would increase the susceptibility to and severity of heat stroke (HS). What is the main finding and its importance? We provide the first experimental evidence, using a mouse model of HS, that recent viral illness increases the severity of HS. Our data indicate that this effect is not attributable to the exacerbation of hyperthermia but is a consequence of ongoing coagulation and systemic inflammatory reactions.

Biochemical recovery from exertional heat stroke follows a 16-day time course.

Background: The aim of this study was to characterize the time-resolved progression of clinical laboratory disturbances days-following an exertional heat stroke (EHS). Currently, normalization of organ injury clinical biomarker values is the primary indicator of EHS recovery. However, an archetypical biochemical recovery profile following EHS has not been established.

Delayed metabolic dysfunction in myocardium following exertional heat stroke in mice.

Key Points: Exposure to exertional heat stroke (EHS) is associated with increased risk of long-term cardiovascular disorders in humans. We demonstrate that in female mice, severe EHS results in metabolic changes in the myocardium, emerging only after 9-14 days. This was not observed in males that were symptom-limited at much lower exercise levels and heat loads compared to females.

Serum and peritoneal exudate concentrations after high doses of β-lactams in critically ill patients with severe intra-abdominal infections: an observational prospective study.

Background: Critically ill patients with severe intra-abdominal infections (IAIs) requiring surgery may undergo several pharmacokinetic (PK) alterations that can lead to β-lactam underdosage.

Objectives: To measure serum and peritoneal exudate concentrations of β-lactams after high doses and optimal administration schemes.

Methods: This observational prospective study included critically ill patients with suspicion of IAI who required surgery and a β-lactam antibiotic as empirical therapy.

Controversies in exertional heat stroke diagnosis, prevention, and treatment.

During the past several decades, the incidence of exertional heat stroke (EHS) has increased dramatically. Despite an improved understanding of this syndrome, numerous controversies still exist within the scientific and health professions regarding diagnosis, pathophysiology, risk factors, treatment, and return to physical activity. This review examines the following eight controversies: ) reliance on core temperature for diagnosing and assessing severity of EHS; ) hypothalamic damage induces heat stroke and this mediates "thermoregulatory failure" during the immediate recovery period; ) EHS is a predictable condition primarily resulting from overwhelming heat stress; ) heat-induced endotoxemia mediates systemic inflammatory response syndrome in all EHS cases; ) nonsteroidal anti-inflammatory drugs for EHS prevention; ) EHS shares similar mechanisms with malignant hyperthermia; ) cooling to a specific body core temperature during treatment for EHS; and ) return to physical activity based on physiological responses to a single-exercise heat tolerance test.

Influence of prior illness on exertional heat stroke presentation and outcome.

Introduction: Precipitating factors that contribute to the severity of exertional heat stroke (EHS) are unclear. The purpose of this study was to determine the effect of prior illness (PI) on EHS severity.

Methods: We performed a retrospective clinical record review of 179 documented cases of EHS at the Marine Corps Base in Quantico, Virginia.

Use of the heat tolerance test to assess recovery from exertional heat stroke.

Exercise or work in hot environments increases susceptibility to exertional heat illnesses such as exertional heat stroke (EHS). EHS occurs when body heat gain exceeds body heat dissipation, resulting in rapid body heat storage and potentially life-threatening consequences. EHS poses a dangerous threat for athletes, agriculture workers, and military personnel, as they are often exposed to hot environmental conditions that restrict body heat loss or contribute to body heat gain.

Sex-dependent responses to exertional heat stroke in mice.

With increasing participation of females in endurance athletics and active military service, it is important to determine if there are inherent sex-dependent susceptibilities to exertional heat injury or heat stroke. In this study we compared responses of male and female adult mice to exertional heat stroke (EHS). All mice were instrumented for telemetry core temperature measurements and were exercise-trained for 3 wk before EHS.

Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke.

It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (T) of male, C57BL/6J mice ( = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating.

Unique cytokine and chemokine responses to exertional heat stroke in mice.

Unlabelled: In heat stroke, cytokines are believed to play important roles in multiorgan dysfunction and recovery of damaged tissue. The time course of the cytokine response is well defined in passive heat stroke (PHS), but little is known about exertional heat stroke (EHS). In this study we used a recently developed mouse EHS model to measure the responses of circulating cytokines/chemokines and cytokine gene expression in muscle.

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

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.

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

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.