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

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane-susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH-susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity.
 ...
PMID:Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome. 142 16

We investigated Greyhounds because of prior reports of malignant hyperthermia (MH) episodes and because Greyhounds may express high genetic relatedness due to inbreeding for generations. Seven Greyhound and six mongrel dogs were given halothane and succinylcholine anesthesia as a challenge to trigger MH. They also underwent semitendinosus muscle biopsy for contracture study with halothane and caffeine. Measurements in vivo of mixed venous and arterial blood gases, cardiac output by thermodilution, temperature, blood pressure, and pulse rate provided sequential data regarding whole body O2 consumption (product of cardiac output and arterial-mixed venous O2 content difference), acid-base status, and arterial CO2 tension. Greyhounds and mongrels had uniformly similar in vivo and in vitro responses, without evidence for MH. Contracture thresholds were higher than those reported for normal swine and humans (8 mM vs. 4 mM). Information on MH susceptibility in this breed is important for laboratory investigation in Greyhounds as well as to veterinary medicine in general. Neither mongrels nor this group of Greyhounds were obviously susceptible to MH. If all Greyhounds are genetically homologous, then Greyhounds may not be specifically MH susceptible. These findings overall may provide a protocol and baseline normal comparative data for determining MH susceptibility in dogs and other species.
 ...
PMID:Evaluation of greyhound susceptibility to malignant hyperthermia using halothane-succinylcholine anesthesia and caffeine-halothane muscle contractures. 146 Aug 48

Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization-induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization-induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm.
 ...
PMID:[The effect of muscle relaxants on masseter tone. An experimental study in an MH-susceptible swine model]. 161 14

The authors report on the course of a fulminant malignant hyperthermia (MH) associated with laminectomy in a 29-year-old man who had been healthy up to that time. Succinylcholine and isoflurane were considered to be the causative triggering agents. Progression could be prevented due to an early suspicion raised by end-expiratory CO2 measurement: treatment was instituted immediately (Dantrolene 2mg/kg body weight, oxygen hyperventilation, external cooling, etc.) Serum creatine kinase increased up to almost 50,000 U/l associated with massive myoglobinuria. Residue-free restitution was achieved within a few days. Decisive for an early detection of MH is the routine performance of end-expiratory CO2 measurement which is definitely superior to temperature control and significantly reduces the time that elapses before treatment is initiated.
 ...
PMID:[The early diagnosis of malignant hyperthermia--the place of end-expiratory CO2 monitoring]. 178 8

We report on the fulminant crisis of malignant hyperthermia occurring in a 30-year-old female during kidney transplantation. In the past, she had been anaesthetised repeatedly without complications. Anaesthesia was induced with thiopental and vecuronium and continued with isoflurane/N2O/O2. After an initially normal course of anaesthesia, the patient developed symptoms of a fulminant malignant hyperthermia (MH) including excessive increase in end expiratory CO2, hyperkalaemia, tachycardia and hyperpyrexia. The patient was saved by the timely administration of dantrolene. A surgical revision required the next day because of bleeding was done under dantrolene cover and took an uncomplicated course. The patient was extubated 7.5 hours after the second intervention and transferred to a normal ward after 4 days. A subsequently performed in vitro contracture test clearly revealed susceptibility to malignant hyperthermia.
 ...
PMID:[Fulminant malignant hyperthermia during the 6th general anesthesia using volatile anesthetics]. 178 10

Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Desflurane is a trigger of malignant hyperthermia in susceptible swine. 190 Mar 98

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.
 ...
PMID:Malignant hyperthermia in dogs. 203 26

Cardiac arrests (CA) occurring during anaesthesia and recovery can be classified into three groups: CA not related to anaesthesia (NACA), CA related to anaesthesia (ACA), whether partially (PACA) or totally (TACA). In the French survey, NACAs were three times more frequent than ACAs. Nearly 25% of ACAs occurred at induction and consisted mainly in TACAs. Another quarter of ACAs occurred during maintenance and consisted mainly in PACAs. About 50% of ACAs occurred after the end of anaesthesia and had the highest mortality rate. Cardiac arrest corresponds to the status of a heart unable to generate the minimum aortic blood flow required for functioning of vital organs. For the brain, a zero-blood flow of more than 4 seconds results in coma. Consequently CA exists when the time interval between two subsequent efficient systoles is greater than 4 seconds. Anaesthetic agents can result in CA by 1) overdose (absolute, relative), 2) anaphylactoid/anaphylactic reactions, 3) specific effects (acetylcholine-like effect, hyperkalaemia and malignant hyperthermia for succinylcholine; vagal effect of vecuronium and atracurium; cardiotoxicity of bupivacaine) and 4) drug interaction. In hypoxic CA, severe neurologic impairment often still exists at the time of onset of CA. The anaesthesia machine and controlled ventilation can induce CA by hypoxic ventilation, overdose of anaesthetic vapour, excessive CO2 reinhalation, hypoventilation, disconnection, excessive pressure in airways. Cardiac hypothermia can be a cause of CA as well as a cause of unsuccessful CPR. Massive infusion of unwarmed fluids and IPPV with unheated gases generate a temperature gradient within the heart which may result in severe arrhythmias and CA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Cardiac arrest during anesthesia and recovery period]. 214 88

An automatic feed back controlled totally closed circuit system (Physioflex) has been developed for quantitative practice of inhalation anesthesia and ventilation. In the circuit system the gas is moved unidirectionally around by a blower at 70 l/min. In the system four membrane chambers are integrated for ventilation. Besides end-expiratory feed back control of inhalation anesthetics, and inspiratory closed loop control of oxygen, the system offers on-line registration of flow, volume and respiratory pressures as well as a capnogram and oxygen consumption. Alveolar ventilation and static compliance can easily be derived. On-line registration of oxygen consumption has proven to be of value for determination of any impairment of tissue oxygen supply when the oxygen delivery has dropped to critical values. Obstruction of the upper or lower airways are immediately detected and differentiated. Disregulations of metabolism, e.g. in malignant hyperthermia, are seen in a pre-crisis phase (increase of oxygen consumption and of CO2 production), and therapy can be started extremely early and before a disastrous condition has developed. Registration of compliance is only one of the continuously available parameters that guarantee a better and adequate control of lung function (e.g. atalectasis is early detected). The newly developed sophisticated anesthesia device enlarges tremendously the monitoring and respiratory diagnostic possibilities of artificial ventilation, gives new insights in the (patho)physiology and detects disturbances of respiratory parameters and metabolism in an early stage.
 ...
PMID:Respiratory diagnostic possibilities during closed circuit anesthesia. 226 Apr 24

Malignant hyperthermia (MH) is a pharmacogenetic disorder. It is classically described as a hypermetabolic state triggered by halogenated anaesthetics and/or depolarizing muscle relaxants. In fact, since Denborough and Lovel's case, it has been shown that MH has a great number of clinical forms. The overwhelming picture of muscular hypercatabolism with fulminating hyperthermia and generalized rigidity is becoming rare. A better knowledge of the first symptoms explains in part the better prognosis: masseter spasm after suxamethonium, an increase in expired CO2 concentration, unexplained tachycardia, ventricular arrhythmias. The use of dantrolene reduced the mortality of MH. The different types of clinical manifestations are due to genetic differences, the concentration of the anaesthetic agent, and the length of time of exposure to the drug. The severity of the episode is linked to environmental factors such as stress, physical exercise, ambient temperature, concomitant use of other drugs. Masseter spasm after suxamethonium is specific for MH, but not pathognomonic. It occurs in 1% of cases in children when using halothane with suxamethonium. However, in those patients who displayed such a spasm, more than 50% had a positive contracture test. Masseter spasm is often associated with severe rhabdomyolysis in patients with muscle dystrophy, especially Duchenne's dystrophy. In the latter case, major cardiac problems may occur at the time of anaesthetic induction. Even if there are no other signs of MH, all patients who have had a masseter spasm must be considered as open to doubt, and should be further explored. MH is often difficult to diagnose in medium severity types.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical features of malignant hyperthermia crisis]. 251 11


1 2 3 4 5 Next >>