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3.
J Surg Res ; 171(2): 762-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20673918

ABSTRACT

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.


Subject(s)
Anticoagulants/pharmacology , Chondroitin Sulfates/pharmacology , Dermatan Sulfate/pharmacology , Heat Exhaustion/drug therapy , Heat Stroke/prevention & control , Heparitin Sulfate/pharmacology , Acute Disease , Animals , Antithrombin III , Cytokines/blood , Disease Models, Animal , Fibrin Fibrinogen Degradation Products/metabolism , HMGB1 Protein/blood , Heat Exhaustion/immunology , Heat Exhaustion/pathology , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Intestine, Small/drug effects , Intestine, Small/pathology , Liver/drug effects , Liver/pathology , Lung/drug effects , Lung/pathology , Male , Nitrates/blood , Nitric Oxide/blood , Nitrites/blood , Peptide Hydrolases/blood , Rats , Rats, Wistar , Survival Rate
4.
Exerc Sport Sci Rev ; 32(4): 174-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15604937

ABSTRACT

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.


Subject(s)
Heat Stress Disorders/physiopathology , Malignant Hyperthermia/physiopathology , Physical Exertion , Acidosis/genetics , Acidosis/metabolism , Adolescent , Child , Dantrolene/therapeutic use , Fatal Outcome , Genetic Predisposition to Disease , Heat Exhaustion/drug therapy , Heat Exhaustion/genetics , Heat Exhaustion/physiopathology , Heat Stress Disorders/drug therapy , Heat Stress Disorders/genetics , Humans , Male , Malignant Hyperthermia/drug therapy , Malignant Hyperthermia/genetics , Muscle Relaxants, Central/therapeutic use , Mutation , Risk Factors , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/metabolism
5.
J Appl Physiol (1985) ; 97(4): 1275-82, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15358751

ABSTRACT

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.


Subject(s)
Amino Acids, Branched-Chain/administration & dosage , Dehydration/drug therapy , Dehydration/physiopathology , Dietary Supplements , Heat Exhaustion/drug therapy , Heat Exhaustion/physiopathology , Physical Endurance/drug effects , Psychomotor Performance/drug effects , Adult , Dehydration/etiology , Heat Exhaustion/complications , Humans , Male , Physical Exertion/drug effects , Treatment Outcome
6.
J Appl Physiol (1985) ; 96(3): 951-6, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14657039

ABSTRACT

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.


Subject(s)
Dietary Proteins/administration & dosage , Exercise/physiology , Military Medicine , Muscle Fatigue/drug effects , Adolescent , Analysis of Variance , Body Composition/drug effects , Body Composition/physiology , Dietary Supplements , Double-Blind Method , Health , Heat Exhaustion/drug therapy , Heat Exhaustion/physiopathology , Humans , Male , Muscle Fatigue/physiology , South Carolina
7.
Anaesthesia ; 48(12): 1057-60, 1993 Dec.
Article in English | MEDLINE | ID: mdl-7904429

ABSTRACT

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.


Subject(s)
3,4-Methylenedioxyamphetamine/analogs & derivatives , Dantrolene/therapeutic use , Designer Drugs , Heat Exhaustion/drug therapy , Substance-Related Disorders/drug therapy , Adolescent , Adult , Blood Coagulation Disorders/chemically induced , Dancing , Female , Fever/chemically induced , Fever/drug therapy , Humans , Male , N-Methyl-3,4-methylenedioxyamphetamine , Renal Insufficiency/chemically induced , Rhabdomyolysis/chemically induced
8.
Crit Care Med ; 20(8): 1192-3, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1643904
10.
Crit Care Med ; 19(2): 176-80, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1989755

ABSTRACT

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.


Subject(s)
Dantrolene/therapeutic use , Heat Exhaustion/drug therapy , Double-Blind Method , Female , Heat Exhaustion/complications , Heat Exhaustion/therapy , Humans , Length of Stay , Male , Middle Aged
11.
Kosm Biol Aviakosm Med ; 24(6): 53-5, 1990.
Article in Russian | MEDLINE | ID: mdl-1981379

ABSTRACT

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.


Subject(s)
Disease Models, Animal , Heat Exhaustion/drug therapy , Hyperthermia, Induced/adverse effects , Stress, Physiological/drug therapy , Adrenergic Agonists/administration & dosage , Amobarbital/administration & dosage , Animals , Drug Therapy, Combination , Female , Heat Exhaustion/etiology , Male , Rats , Stress, Physiological/etiology , Tranquilizing Agents/administration & dosage
12.
Med J Aust ; 153(9): 565-6, 1990 Nov 05.
Article in English | MEDLINE | ID: mdl-2233489
13.
Crit Care Med ; 18(3): 290-2, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2302955

ABSTRACT

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.


Subject(s)
Dantrolene/therapeutic use , Heat Exhaustion/drug therapy , Body Temperature Regulation/drug effects , Body Weight , Female , Heat Exhaustion/physiopathology , Humans , Male , Middle Aged
14.
Patol Fiziol Eksp Ter ; (5): 32-4, 1989.
Article in Russian | MEDLINE | ID: mdl-2616212

ABSTRACT

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.


Subject(s)
Butylated Hydroxytoluene/therapeutic use , Heat Exhaustion/drug therapy , Kidney/drug effects , Animals , Citric Acid Cycle/drug effects , Drug Evaluation, Preclinical , Glycolysis/drug effects , Heat Exhaustion/metabolism , Heat Exhaustion/mortality , Kidney/metabolism , Male , Oxidation-Reduction/drug effects , Rats
18.
Am J Emerg Med ; 4(5): 399-405, 1986 Sep.
Article in English | MEDLINE | ID: mdl-3741558

ABSTRACT

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.


Subject(s)
Dantrolene/therapeutic use , Disease Models, Animal , Heat Exhaustion/drug therapy , Animals , Creatine Kinase/blood , Creatinine/blood , Dantrolene/pharmacology , Dogs , Heat Exhaustion/blood , Heat Exhaustion/pathology , Heat Exhaustion/physiopathology , Hemodynamics/drug effects , Isoenzymes/blood
19.
Poult Sci ; 65(9): 1659-63, 1986 Sep.
Article in English | MEDLINE | ID: mdl-3022276

ABSTRACT

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.


Subject(s)
Ammonium Chloride/therapeutic use , Bicarbonates/therapeutic use , Chickens , Heat Exhaustion/veterinary , Poultry Diseases/prevention & control , Sodium/therapeutic use , Animals , Blood Chemical Analysis/veterinary , Drinking , Heat Exhaustion/drug therapy , Heat Exhaustion/prevention & control , Hydrogen-Ion Concentration , Male , Poultry Diseases/drug therapy , Sodium Bicarbonate
20.
Drugs ; 32(2): 130-68, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3527659

ABSTRACT

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.


Subject(s)
Dantrolene/therapeutic use , Malignant Hyperthermia/drug therapy , Muscle Spasticity/drug therapy , Neuroleptic Malignant Syndrome/drug therapy , Animals , Calcium/metabolism , Central Nervous System/drug effects , Dantrolene/adverse effects , Dantrolene/blood , Dantrolene/pharmacology , Endocrine Glands/drug effects , Heat Exhaustion/drug therapy , Humans , Kinetics , Malignant Hyperthermia/prevention & control , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Myocardial Contraction/drug effects , Neuromuscular Junction/drug effects , Respiration/drug effects
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