Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation-contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 +/- 58 to 159 +/- 57 nmol.min-1.mg-1 (mU/mg) and from 577 +/- 82 to 177 +/- 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 +/- 2.4 to 3.11 +/- 0.67 nM/s at 300 nM Ca and 38.7 +/- 10.5 to 16.3 +/- 8.0 nM/s at 1500 nM Ca, respectively (all p less than 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p less than 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac and muscle fatigue due to relative functional overload induced by excessive stimulation, hypersensitive excitation-contraction coupling, or diminished performance capacity correlates with sarcoplasmic reticulum failure. 205 42

We have performed the tourniquet-twitch test of Roberts and Ryan in normal and in malignant hyperthermia (MH) patients and relatives. This test measures the ratio of electrically induced thumb twitches noted after 10 min of ischemia with those noted immediately prior to the ischemia. We found no significant differences in this ratio between normal subjects and those who have had MH reactions, or relatives of such individuals. Furthermore, we have observed no significant differences in tourniquet-twitch ratios between those with normal caffeine-halothane contractures and persons with caffeine-halothane contractures tests positive for MH. These findings do not agree with those of Roberts and Ryan, who reported that tourniquet-twitch ratios were higher in MH patients than in normal patients. We have, however, determined that subjects with tourniquet-twitch ratios greater than or equal to 1.8 are substantially younger than those with tourniquet-twitch ratios less than or equal to 1.0. Therefore we do not believe that the tourniquet-twitch test is useful as a diagnostic, or even as a screening test for MH.
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PMID:Failure of the tourniquet-twitch test as a diagnostic or screening test for malignant hyperthermia. 375 52

The effect was examined of dantrolene, a drug for malignant hyperthermia acting through preventing release of Ca from the ryanodine-type intracellular stores in muscle cells, on ischemic delayed neuronal death in field CA1 of gerbil hippocampus. Dantrolene (1.6 mM in concentration, 3 microliters each in volume), when administered bilaterally in the lateral ventricles 30 min after reperfusion after transient forebrain ischemia for 3 min at 37 degrees C, significantly protected against the neuronal death. It is proposed that the dantrolene-sensitive (most likely, the ryanodine-type) intracellular Ca stores in CA1 pyramidal cells play a pivotal role in the development of ischemic neuronal damage.
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PMID:Dantrolene protects against ischemic, delayed neuronal death in gerbil brain. 823 63

Malignant hyperthermia is a complication of general anesthesia that is especially problematic if it occurs during renal transplantation because myoglobinemia, shock, and ischemia play a role in injuring the transplanted kidney. In this report, we describe a case of malignant hyperthermia, its clinical course, and the measures taken to successfully treat it and preserve the function of a kidney allograft.
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PMID:Successful treatment of intraoperative malignant hyperthermia during renal transplantation. 866 18

The purpose of this study was to describe the perceptions of nurse anesthesia students (NAS) who used a MedSim simulator (MedSim USA, Inc, Ft Lauderdale, Fla) as part of their educational training. A convenience sample of 12 NAS in their first year of clinical training was researched. The researcher analyzed data qualitatively from observations made during 4 different sessions. Session 1 introduced the students to the simulator. Session 2 involved each student performing an anesthetic induction. A minor incident such as hypotension, hypertension, bradycardia or tachycardia occurred in session 3, and a major incident such as cardiac ischemia, anaphylaxis, bronchospasm, or malignant hyperthermia occurred in session 4. Data collection involved observation by the primary investigator, journal entries by the anesthesia students, and focus group interviews with the students. Results of the study indicate that, although students experience feelings of apprehension, uneasiness, or fear during the sessions, they felt it was very educational. Disadvantages include the lack of reality, lack of knowledge on handling crisis events, possibility of fixation errors, and the presence of anxiety. Advantages include improved critical thinking and decision-making skills, increased confidence, and improved clinical preparation. Results can be used to assist instructors in improving the students' learning experiences and to teach more effectively.
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PMID:Nurse anesthesia students' perceptions of the anesthesia patient simulator: a qualitative study. 1207 70

Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica. The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 degrees F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica. This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.
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PMID:Yersinia septic shock following an autologous transfusion in a pediatric patient. 1262 Feb 65

Calcium, as a second messenger, has an important role in a variety of cellular functions. However, disruption of intracellular calcium homeostasis leads to cytotoxicity and cell death. Excessive calcium release from intracellular stores, via the calcium channel ryanodine receptor, contributes to cell damage. Dysfunction of calcium homeostasis is established in tissue culture and animal models of ischemia, hypoxia, seizure, trauma, anesthesia, and neurodegenerative diseases. Dantrolene, the primary drug to treat malignant hyperthermia, is a ryanodine receptor antagonist. Dantrolene inhibits abnormal calcium release from the sarco-endoplasmic reticulum, which is the primary intracellular calcium store. Dantrolene has been investigated widely for its possible cytoprotective effects against cell damage in different tissue culture or animal models of diseases involving cytotoxicity induced by disruption of intracellular calcium homeostasis in pathogenesis. In this review, we summarize the role of the disruption of intracellular calcium homeostasis on cell death, the pharmacologic and pharmacokinetic features of dantrolene, and the cytoprotective effects and potential application of dantrolene for the inhibition of cell damage in a wide variety of models of stress and disease.
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PMID:The cytoprotective effects of dantrolene: a ryanodine receptor antagonist. 2086 18

Dantrolene, an FDA approved drug to treat malignant hyperthermia and muscle spasm, has been demonstrated to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediated toxicity of host cells. Ryanodine receptor overactivation and associated disruption of intracellular Ca2+ homeostasis play important roles in SARS-CoV-2 infection and replication of host cells. Dantrolene, as an inhibitor of RyRs, is expected to ameliorate these detrimental effects of SARS-CoV-2 in host cells. Additionally, dantrolene has also been shown to inhibit multiple cell or organ damage induced by hypoxia/ischemia, mitochondria damage, oxidative stresses, inflammation, impairment of autophagy and apoptosis, etc., which are often the causes of severity and mortality of COVID-19 patients. We have repurposed that dantrolene has a high potential at treating COVID-19 patients and reducing its morbidity and mortality.
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PMID:Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis? 3309 Apr 34