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Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients.
J Clin Anesth. 2000 Mar; 12(2):123-8.JC

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.

Authors+Show Affiliations

Department of Anesthesiology, University-Hospital Eppendorf, Hamburg, Germany. fiege@uke.uni-hamburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

10818326

Citation

Fiege, M, et al. "Effects of the phosphodiesterase-III Inhibitor Enoximone On Skeletal Muscle Specimens From Malignant Hyperthermia Susceptible Patients." Journal of Clinical Anesthesia, vol. 12, no. 2, 2000, pp. 123-8.
Fiege M, Wappler F, Scholz J, et al. Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients. J Clin Anesth. 2000;12(2):123-8.
Fiege, M., Wappler, F., Scholz, J., Weisshorn, R., von Richthofen, V., & Schulte am Esch, J. (2000). Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients. Journal of Clinical Anesthesia, 12(2), 123-8.
Fiege M, et al. Effects of the phosphodiesterase-III Inhibitor Enoximone On Skeletal Muscle Specimens From Malignant Hyperthermia Susceptible Patients. J Clin Anesth. 2000;12(2):123-8. PubMed PMID: 10818326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients. AU - Fiege,M, AU - Wappler,F, AU - Scholz,J, AU - Weisshorn,R, AU - von Richthofen,V, AU - Schulte am Esch,J, PY - 2000/5/20/pubmed PY - 2000/7/8/medline PY - 2000/5/20/entrez SP - 123 EP - 8 JF - Journal of clinical anesthesia JO - J Clin Anesth VL - 12 IS - 2 N2 - 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. SN - 0952-8180 UR - https://www.unboundmedicine.com/medline/citation/10818326/Effects_of_the_phosphodiesterase_III_inhibitor_enoximone_on_skeletal_muscle_specimens_from_malignant_hyperthermia_susceptible_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0952-8180(00)00124-0 DB - PRIME DP - Unbound Medicine ER -