Síndrome serotoninérgico durante una ola de calor / Serotonin syndrome during a heat wave

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Danaparoid sodium attenuates the effects of heat stress.

BACKGROUND: Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke. MATERIALS AND METHODS: Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples. RESULTS: In rats pretreated with DA, induction of cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation. CONCLUSION: Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.

Is there a link between malignant hyperthermia and exertional heat illness?

Exertional heat illness (EHI) and malignant hyperthermia (MH) are two potentially lethal conditions. It has been suggested that a subset of MH susceptible persons may be predisposed to EHI. We examine the current understanding of these disorders and explore evidence of a relationship. Screening for the muscle type I ryanodine receptor gene should help clarify the relationship between MH and EHI.

Branched-chain amino acid supplementation and human performance when hypohydrated in the heat.

The serotonin system may contribute to reduced human performance when hypohydrated in the heat. This study determined whether branched-chain amino acid (BCAA) supplementation could sustain exercise and cognitive performance in the heat (40 degrees C dry bulb, 20% relative humidity) when hypohydrated by 4% of body mass. Seven heat-acclimated men completed two experimental trials, each consisting of one preparation and one test day. On day 1, a low-carbohydrate diet was eaten and subjects performed exhaustive cycling (morning) and treadmill exercise in the heat (afternoon) to lower muscle glycogen and achieve the desired hypohydration level. On day 2, subjects consumed an isocaloric BCAA and carbohydrate (BC) or carbohydrate-only drink during exercise. Experimental trials included 60 min of cycle ergometry (50% peak oxygen uptake) followed by a 30-min time trial in the heat. A cognitive test battery was completed before and after exercise, and blood samples were taken. BC produced a 2.5-fold increase (P < 0.05) in plasma BCAA and lowered (P < 0.05) the ratios of total tryptophan to BCAA and large neutral amino acid. Blood prolactin, glucose, lactate, and osmolality were not different between trials but increased over time. Cardiovascular and thermoregulatory data were also similar between trials. BC did not alter time-trial performance, cognitive performance, mood, perceived exertion, or perceived thermal comfort. We conclude that BCAA does not alter exercise or cognitive performance in the heat when subjects are hypohydrated.

Postexercise protein supplementation improves health and muscle soreness during basic military training in Marine recruits.

Elevated postexercise amino acid availability has been demonstrated to enhance muscle protein synthesis acutely, but the long-term impact of postexercise protein supplementation on variables such as health, muscle soreness, and function are unclear. Healthy male US Marine recruits from six platoons (US Marine Corps Base, Parris Island, SC; n = 387; 18.9 +/- 0.1 yr, 74.7 +/- 1.1 kg, 13.8 +/- 0.4% body fat) were randomly assigned to three treatments within each platoon. Nutrients supplemented immediately postexercise during the 54-day basic training were either placebo (0 g carbohydrate, 0 g protein, 0 g fat), control (8, 0, 3), or protein supplement (8, 10, 3). Subjects and observers making measurements and data analysis were blinded to subject groupings. Compared with placebo and control groups, the protein-supplemented group had an average of 33% fewer total medical visits, 28% fewer visits due to bacterial/viral infections, 37% fewer visits due to muscle/joint problems, and 83% fewer visits due to heat exhaustion. Recruits experiencing heat exhaustion had greater body mass, lean, fat, and water losses. Muscle soreness immediately postexercise was reduced by protein supplementation vs. placebo and control groups on both days 34 and 54. Postexercise protein supplementation may not only enhance muscle protein deposition but it also has significant potential to positively impact health, muscle soreness, and tissue hydration during prolonged intense exercise training, suggesting a potential therapeutic approach for the prevention of health problems in severely stressed exercising populations.

Exertional heat stroke induced by amphetamine analogues. Does dantrolene have a place?

There are increasing numbers of patients admitted to hospital as a result of ingesting amphetamine-like drugs. The most severe cases exhibit hyperthermia, rhabdomyolysis, coagulopathy and renal failure. We describe six such patients with varying severity of intoxication, and have reviewed the recent literature with particular reference to the use of dantrolene. One of our patients died but the others all survived. There is little evidence that dantrolene influenced the outcome in patients reported to date. We believe that a controlled trial should be carried out in amphetamine-related hyperthermia before the use of dantrolene becomes widespread.

Ineffectiveness of dantrolene sodium in the treatment of heatstroke.

STUDY OBJECTIVE: To determine the efficacy of dantrolene sodium in the treatment of heatstroke. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Heatstroke center in Makkah, Saudi Arabia. PATIENTS: Fifty-two adult patients with heatstroke. INTERVENTIONS: Patients were assigned to receive either dantrolene sodium (2 mg/kg body weight iv) or placebo. Conventional cooling therapy was initiated in all. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in the mean cooling times for the treatment and control groups (67.9 vs. 69 min). There was only one death in the control group. Complications were seen in six (23%) patients receiving dantrolene sodium and seven (27%) patients receiving placebo; the difference was not statistically significant. There was no significant difference in the mean number of hospital days (4.7 +/- 2.0 vs. 2.9 +/- 0.9 days). CONCLUSION: Treatment with dantrolene sodium at the dose used, did not prove beneficial to patients with heatstroke.

[Pharmacological correction of stress reactions after hyperthermia]. / Farmakologicheskaia korrektsiia stressovoi reaktsii pri gipertermii.

It was demonstrated experimentally that aminazine, phentolamine, nuredal, sapilent, teperin, dopegyt improved significantly the health status of animals exposed to high temperature and in many cases prevented their death. This gives evidence that the sympathetic nervous system plays a leading role in heat stroke and that sympathotrophic drugs can be used for protective purpose during acute overheating.

Is dantrolene effective in heat stroke patients?

Dantrolene (2.45 mg/kg body weight, range 2 to 4) was administered iv in eight heat stroke (HS) patients and compared with a control group of 12 patients of similar age, weight, and temperature range (41.9 degrees to 44 degrees C). Body surface cooling was conducted in air conditioned rooms at temperatures of 18 degrees to 23 degrees C. Mean cooling time in the dantrolene group was 49.7 +/- 4.4 (SEM) min, whereas cooling time in the control group was 69.2 +/- 4.8 min. The decrease in temperature was significantly greater in the dantrolene group, for whom the cooling time was decreased by about 19.5 min (p less than .01). Although cooling time was significantly shorter in the dantrolene group, there was no difference in the recovery of both groups. Dantrolene is an expensive drug and justification for its routine use in HS remains to be evaluated.

[The effect of ionol on oxidative-reductive processes in the kidney during heat stroke]. / Vliianie ionola na okislitel'no-vosstanovitel'nye protsessy v pochke pri teplovom udare.

Heat stroke was induced in intact rats in a thermal chamber (45 degrees C) and simultaneously a group of animals was subjected to overheating for the same time but was given intraperitoneal injections of ionol (120 mg/kg) for 2 days and 30 minutes before exposure in the chamber. Significant increase of the concentration of intermediates--lactate, pyruvate, malate, glutamate, ammonia--and decrease of the alpha-ketoglutarate content occurred in the renal tissue in animals of both groups. The NAD/NADH ratio in the cytoplasm and mitochondria reduced essentially, to a greater degree in animals given ionol injections. The last named were distinguished by higher survival and lower degree of hyperthermia.

Dantrolene sodium for treatment of heatstroke victims: lack of efficacy in a canine model.

Dantrolene sodium, a skeletal-muscle relaxant known to be effective for treatment of malignant hyperthermia, was evaluated for efficacy in treatment of heatstroke. Non-exertional heatstroke was induced in 11 dogs by external heating following barbiturate anesthesia. When core temperature reached 43 degrees C (109.4 degrees F) heating was discontinued and control animals (n = 6) were allowed to cool passively in room air. Treatment animals (n = 5) received 5 mg/kg dantrolene sodium intravenously at the start of room-air cooling. Serial temperatures (pulmonary arterial, rectal, cerebral, and subcutaneous), blood chemistry tests (including electrolytes, liver enzymes, and complete blood count), and hemodynamic parameters (including cardiac output, arterial pressure, and urinary output) were followed for 12 hours after induction of heatstroke. Autopsies, including gross and microscopic examination, were performed on all animals. Dantrolene administration did not significantly affect cooling rates, hemodynamic parameters, pathological changes, or clinical outcome. Statistically significant changes in urinary output and serum creatinine observed in the first hours after dantrolene administration can be attributed to the mannitol vehicle in which the drug was delivered. There were no statistically significant differences in these values at 12 hours. Dantrolene sodium does not appear to enhance passive cooling in treatment of non-exertional canine heatstroke.

Use of ammonium chloride and sodium bicarbonate in acute heat exposure of broilers.

Ammonium chloride (NH4Cl) and sodium bicarbonate (NaHCO3) were added separately to the drinking water of 42- to 52-day-old broilers. Birds were given access to the water ad libitum for a total of 42.5 hr consisting of 18.5 hr prior to an 8-hr interval of severe heat exposure and a further 16 hr-post exposure. Water and feed intake during the treatment period were unaffected by either NH4Cl at 6.25 g/liter (.63%) of distilled water (DW) or NaHCO3 at 3.15 g/liter (.32%) DW. Water intake was increased by approximately 20% in birds given water containing 6.25 g of NaHCO3/liter (.63%) DW, while both feed and water intake were severely limited by NH4Cl at 31 g/liter (3.1%) DW. Blood pH of birds was substantially lowered by consumption of NH4Cl, while consumption of NaHCO3 did not significantly affect blood pH. Blood pH of all treatments increased during the heat exposure period and declined afterward; however, blood pH change appeared to be more pronounced for birds receiving the NH4CL. A correlation coefficient (r = -.31) existed between blood pH and mortality, while a correlation (r = -.72) was demonstrated between water consumption and mortality.

Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity.

Dantrolene sodium acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle. Recently, dantrolene has been used very successfully in the treatment of several rare hypercatabolic syndromes which have previously been associated with high mortality rates. In malignant hyperthermia, where early diagnosis and treatment usually with intravenous dantrolene in association with other supportive measures (and often subsequent dantrolene therapy) is performed, recovery is seen in virtually 100% of patients. There is a rapid resolution of hyperthermia, dysrhythmias, muscle rigidity, tachycardia, hypercapnia, mottled or cyanotic skin, and metabolic acidosis, and a slower normalisation of myoglobinuria and elevated serum creatine phosphokinase levels. In patients with family history or previous episodes of malignant hyperthermia, prophylactic treatment with dantrolene prior to anaesthesia prevents the syndrome occurring in most cases. Where malignant hyperthermia has developed patients have been successfully treated with further dantrolene therapy. Dantrolene has also been used successfully in the treatment of a few cases of heat stroke and the neuroleptic malignant syndrome--both of which have many similarities to malignant hyperthermia. Dantrolene is well established in the treatment of patients with muscle spasticity where it generally improves at least some of the components of spasticity (i.e. hyper/hypotonia, clonus, muscle cramps and spasms, resistance to stretch and flexor reflexes, articular movement, neurological and motor functions and urinary control). However, in some patients, particularly those with multiple sclerosis, dantrolene may not be effective, and in many cases muscular strength may diminish. Long term dantrolene therapy has been associated with hepatic toxicity and may cause problems in patients treated for disorders of muscle spasticity. Thus, dantrolene offers a unique advance in the therapy available for the treatment of hypercatabolic disorders and is also useful in the treatment of muscle spasticity of various aetiology.