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Marko Fiege - One of the best experts on this subject based on the ideXlab platform.

  • Phosphodiesterase III inhibition with amrinone leads to contracture development in skeletal muscle preparations of malignant hyperthermia susceptible swine
    European Journal of Anaesthesiology, 2005
    Co-Authors: Marko Fiege, F Wappler, Ralf Weisshorn, M U Gerbershagen, Kerstin Kolodzie, Schulte Am J Esch
    Abstract:

    SummaryBackground 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 o

  • In vitro and in vivo effects of the Phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.
    Anesthesiology, 2003
    Co-Authors: Marko Fiege, Ralf Weisshorn, M U Gerbershagen, Kerstin Kolodzie, Frank Wappler, Jochen Schulte Am Esch
    Abstract:

    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. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.

  • Effects of the Phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients
    Journal of clinical anesthesia, 2000
    Co-Authors: Marko Fiege, Ralf Weisshorn, Frank Wappler, Jens Scholz, Verena Von Richthofen, Jochen Schulte Am Esch
    Abstract:

    Abstract 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. Patients: 47 patients with clinical suspicion for MH undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. Interventions: Biopsies of M. quadriceps femoris were performed in adult patients with a 3-in-1 nerve block and in children with trigger-free general anesthesia. Measurements and Main Result: Patients were first classified as MHS or MHN by the IVCT according to the protocol of the European MH Group (EMHG). Patients with equivocal results (MHE) or with neuromuscular diseases were excluded from the study. Enoximone was added to the organ bath to surplus vital muscle specimens in single bolus concentrations of 0.4, 0.6, 0.8, or 1.6 mmol/L. The in vitro effects of enoximone on muscle contractures and twitch were measured. Seventeen patients were classified as MHS and 30 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles in a dose-dependent manner. Contractures of MHS compared to MHN muscle specimens were significantly larger at all concentrations used in this study. No overlap in maximum contractures was seen between MHS and MHN muscles at a bath concentration of 0.6 mmol/L enoximone only. Conclusions: Diagnosis of MH by an IVCT test with a single bolus administration of enoximone seems to be possible using a concentration of 0.6 mmol/L. The findings of this study may indicate an involvement of the Phosphodiesterase-III and cAMP system in pathogenesis of MH. Further in vivo investigation should determine the trigger potency of enoximone in MH susceptible individuals.

  • Diagnostik der Disposition zur malignen Hyperthermie durch einen in vitro Kontrakturtest mit dem Phosphodiesterase-III-Hemmstoff Enoximon
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie : AINS, 1998
    Co-Authors: Marko Fiege, F Wappler, Jens Scholz, Verena Von Richthofen, B. Brinken, J. Schulte Am Esch
    Abstract:

    PURPOSE Inhibition of Phosphodiesterase III (PDE-III) by enoximone elevates cyclic AMP (cAMP) content and intracellular calcium in human cardiac muscle. An involvement of cAMP in the pathogenesis of malignant hyperthermia (MH) has been suggested, because a higher basal content of cAMP was found in skeletal muscles from MH susceptible (MHS) than in normal (MHN) individuals and swine. In this study the in vitro effects of enoximone on skeletal muscles and the possibility to distinguish MHS from MHN patients were investigated. METHODS Muscle biopsies from 37 patients with clinical suspicion for MH were obtained. The patients were first classified as MHS, MHE (equivocal result) or MHN by the caffeine halothane contracture tests according to the procedure of the European MH Group (EMHG). MHE-patients and patients with neuromuscular diseases were excluded from the study. Enoximone was added cumulatively every five minutes to surplus muscle specimens to obtain organ bath concentrations of 0.2, 0.4, 0.6, 0.8, 1.2 and 1.6 mmol/l. The in vitro effects of enoximone on muscle contractures and twitch were measured. RESULTS Twelve patients were classified as MHS and 21 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles from all patients. MHS muscles developed contractures at significantly lower bath concentrations of enoximone than MHN muscles. Contractures of MHS compared to MHN muscles were significantly larger at bath concentrations of 0.4, 0.6, 0.8 and 1.2 mmol/l enoximone. No overlap in maximum contractures was seen between MHS and MHN muscles at bath concentrations of 0.6 and 0.8 mmol/l enoximone. Muscle twitch increased in both groups after administration of enoximone. CONCLUSION The PDE-III-inhibitor enoximone induces contracture development in skeletal muscles. These contractures were attained at lower concentrations and were larger in MHS compared to MHN muscles. In vitro diagnosis of MH by a contracture test with enoximone appears to be possible. Furthermore, regarding these results a trigger potency for MH by enoximone could not be proved, but the use of enoximone in MHS patients might be dangerous.

Masaki Okajima - One of the best experts on this subject based on the ideXlab platform.

U. Schildnitz - One of the best experts on this subject based on the ideXlab platform.

Jochen Schulte Am Esch - One of the best experts on this subject based on the ideXlab platform.

  • In vitro and in vivo effects of the Phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.
    Anesthesiology, 2003
    Co-Authors: Marko Fiege, Ralf Weisshorn, M U Gerbershagen, Kerstin Kolodzie, Frank Wappler, Jochen Schulte Am Esch
    Abstract:

    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. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.

  • Effects of the Phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients
    Journal of clinical anesthesia, 2000
    Co-Authors: Marko Fiege, Ralf Weisshorn, Frank Wappler, Jens Scholz, Verena Von Richthofen, Jochen Schulte Am Esch
    Abstract:

    Abstract 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. Patients: 47 patients with clinical suspicion for MH undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility. Interventions: Biopsies of M. quadriceps femoris were performed in adult patients with a 3-in-1 nerve block and in children with trigger-free general anesthesia. Measurements and Main Result: Patients were first classified as MHS or MHN by the IVCT according to the protocol of the European MH Group (EMHG). Patients with equivocal results (MHE) or with neuromuscular diseases were excluded from the study. Enoximone was added to the organ bath to surplus vital muscle specimens in single bolus concentrations of 0.4, 0.6, 0.8, or 1.6 mmol/L. The in vitro effects of enoximone on muscle contractures and twitch were measured. Seventeen patients were classified as MHS and 30 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles in a dose-dependent manner. Contractures of MHS compared to MHN muscle specimens were significantly larger at all concentrations used in this study. No overlap in maximum contractures was seen between MHS and MHN muscles at a bath concentration of 0.6 mmol/L enoximone only. Conclusions: Diagnosis of MH by an IVCT test with a single bolus administration of enoximone seems to be possible using a concentration of 0.6 mmol/L. The findings of this study may indicate an involvement of the Phosphodiesterase-III and cAMP system in pathogenesis of MH. Further in vivo investigation should determine the trigger potency of enoximone in MH susceptible individuals.