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


METHODS
Prospective study.


METHODS
Malignant hyperthermia (MH) laboratory at a university hospital.


METHODS
47 patients with clinical suspicion for MH undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility.


METHODS
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.


RESULTS
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.
Fiege
M
M
Department of Anesthesiology, University-Hospital Eppendorf, Hamburg, Germany. fiege@uke.uni-hamburg.de
Wappler
F
F
Scholz
J
J
Weisshorn
R
R
von Richthofen
V
V
Schulte am Esch
J
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D046508:Culture Techniques; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D017335:Enoximone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000145:classification / Q000175:diagnosis / Q000503:physiopathology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies
D010726:Phosphodiesterase Inhibitors; D017335:Enoximone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3