Effects of theophylline on anesthetized malignant hyperthermia-susceptible pigs.

Background: Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine.

Methods: MH-trigger-free general anesthesia was performed in MHS and MHN swine.

Cumulative and bolus in vitro contracture testing with 4-chloro-3-ethylphenol in malignant hyperthermia positive and negative human skeletal muscles.

In this study we evaluated the in vitro effects of 4-chloro-3-ethylphenol (CEP) using cumulative (12.5-200 micromol/L) or bolus (75 and 100 micromol/L) administrations, on muscle specimens from malignant hyperthermia (MH) susceptible and MH nonsusceptible patients, respectively. In the cumulative CEP in vitro contracture test, contractures were significantly greater in the MH susceptible compared with the MH nonsusceptible muscles in all concentrations between 25 and 100 micromol/L.

Phosphodiesterase-III-inhibition with amrinone leads to contracture development in skeletal muscle preparations of malignant hyperthermia susceptible swine.

Background And Objective: The phosphodiesterase-III (PDE-III) inhibitor enoximone-induced marked contractures in skeletal muscle specimens of malignant hyperthermia (MH) susceptible (MHS) human beings and swine. Whether this is a substance specific effect of enoximone or caused by inhibition of PDE-III remained unclear. Therefore, the effects of the PDE-III inhibitor amrinone in porcine MH normal (MHN) and MHS skeletal muscles were investigated.

Ryanodine contracture threshold times for diagnosis of malignant hyperthermia susceptibility: an experimental approach from a single laboratory.

Study Objectives: To define threshold times for ryanodine contracture testing (RCT) using skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and control individuals.

Design: Prospective study.

Setting: Malignant hyperthermia (MH) laboratory at a university hospital.

Histomorphologic examination of skeletal muscle preparations does not differentiate between malignant hyperthermia-susceptible and -normal patients.

Background: It has been suggested that malignant hyperthermia (MH) can be diagnosed by specific myopathologic alterations. The purpose of this study was to investigate whether there are characteristic myopathologic changes in skeletal muscles of MH-susceptible (MHS) compared with MH-normal (MHN) patients.

Methods: Four hundred forty patients with clinical suspicion of MH were classified as MHN, MH equivocal (MHE), or MHS by the in vitro contracture test with halothane and caffeine.

[Theophylline induces contractures in porcine skeletal muscle preparations with the disposition to malignant hyperthermia].

Objective: Theophylline, a methylxanthine, leads to an increase of the cytoplasmic Ca(2+)-concentration in the muscle cell. Since the in-vitro contracture test (IVCT) with halothane and caffeine does not distinguish a 100% between malignant hyperthermia susceptible (MHS) and non-susceptible (MHN), we examined the in-vitro effects of theophylline in porcine skeletal muscle preparations.

Methods: After approval by the local animal care committee ten MHS- and nine MHN-swine were anaesthetized and muscle biopsies taken.

Dantrolene--a review of its pharmacology, therapeutic use and new developments.

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today.

[Is a presymptomatic malignant hyperthermia in-vitro diagnosis with 4-chloro-3-ethyl phenol possible? A study using porcine skeletal preparations].

Objective: The diagnosis of malignant hyperthermia is currently performed with the in-vitro contracture test (IVCT) with halothane and caffeine. This test has a sensitivity of 99.0 % but only a specificity of 93.

Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine ("ecstasy").

Background: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia. Because of close clinical similarities, an association between MDMA intoxication and malignant hyperthermia (MH) was suggested. The aim of this study was to investigate whether MDMA is a trigger of MH in susceptible swine.

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

Background And Objective: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine.

Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia.

Background: The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved.

In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.

Background: In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated.

Methods: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine.

Results of contracture tests with halothane, caffeine, and ryanodine depend on different malignant hyperthermia-associated ryanodine receptor gene mutations.

Background: More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine.

Methods: Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study.

[In-vitro-effects of cocaine in skeletal muscle specimens of patients susceptible to malignant hyperthermia].

Objective: The abuse of cocaine can cause serious medical complications like tachycardia, rhabdomyolysis, and hyperthermia. Because of the clinical similarities, it has been suggested that cocaine might be a trigger of malignant hyperthermia (MH). Therefore, aim of this study was to investigate the in-vitro effects of cocaine in skeletal muscle specimens of MH susceptible (MHS) and normal (MHN) patients.

Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients.

Study Objectives: To study the in vitro effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible (MHS) and normal (MHN) patients.

Design: Prospective study.

Setting: Malignant hyperthermia (MH) laboratory at a university hospital.

5-HT2 receptor antagonist-mediated inhibition of halothane-induced contractures in skeletal muscle specimens from malignant hyperthermia susceptible patients.

Administration of 5-HT2 receptor agonists induced malignant hyperthermia (MH) in susceptible pigs. Furthermore, the 5-HT2 receptor antagonist ritanserin prevented 5-HT-induced porcine MH. It has been shown that 5-HT2 receptor agonists induce marked contractures in skeletal muscle specimens from MH susceptible (MHS) but not in specimens from normal patients.

4-chloro-m-cresol is a trigger of malignant hyperthermia in susceptible swine.

Background: 4-Chloro-m-cresol (4-CmC) induces marked contractures in skeletal muscle specimens from individuals susceptible to malignant hyperthermia (MHS). In contrast, 4-CmC induces only small contractures in specimens from normal (MHN) patients. 4-CmC is a preservative within a large number of commercially available drug-preparations (e.