PMID- 23138574
OWN - NLM
STAT- MEDLINE
DCOM- 20130524
LR  - 20161125
IS  - 1365-2346 (Electronic)
IS  - 0265-0215 (Linking)
VI  - 30
IP  - 1
DP  - 2013 Jan
TI  - 3,4-Methylenedioxymethamphetamine induces a hyperthermic and hypermetabolic 
      crisis in pigs with and without a genetic disposition for malignant hyperthermia.
PG  - 29-37
LID - 10.1097/EJA.0b013e32835a1127 [doi]
AB  - BACKGROUND: Clinical symptoms of acute 3,4-methylenedioxymethamphetamine (MDMA) 
      intoxication and malignant hyperthermia have many similarities. At present, 
      however, there is contradictory evidence concerning the malignant hyperthermia 
      trigger potency of MDMA. OBJECTIVE: This study was designed to investigate 
      whether MDMA has malignant hyperthermia trigger potential and leads to malignant 
      hyperthermia in pigs with or without a genetic predisposition to the condition. 
      In addition, the therapeutic effectiveness of a new dantrolene sodium suspension 
      was examined. DESIGN: Experimental study, using an animal model of Pietrain pigs. 
      SETTINGS: Institute for Research in Operative Medicine, University of 
      Witten/Herdecke, Hospital Cologne Merheim, Cologne, Germany, October 2006 to 
      February 2007. Trigger-free anaesthesia was performed on seven malignant 
      hyperthermia-susceptible and six malignant hyperthermia-normal Pietrain pigs, and 
      cumulative doses of MDMA were administered to each animal. INTERVENTIONS: After 
      achieving predefined malignant hyperthermia criteria, standardised therapy was 
      initiated; dantrolene sodium suspension (5 mg kg(-1)) was administered and the 
      injection was repeated after 24 min. MAIN OUTCOME MEASURES: The malignant 
      hyperthermia trigger potency of MDMA was analysed by monitoring pH, PaCO2 and 
      temperature. In addition, concentrations of thyroid hormone, mitochondrial 
      uncoupling protein 3, noradrenaline and free fatty acids during administration of 
      MDMA and dantrolene sodium suspension were analysed. RESULTS: MDMA administration 
      led to fulminant hypermetabolic and hyperthermic responses in malignant 
      hyperthermia-susceptible and malignant hyperthermia-normal pigs, with significant 
      decreases in pH (susceptible: pH 7.21 +/- 0.11, normal: pH 7.21 +/- 0.07), severe 
      hypercapnia (susceptible: paCO2 10.3 +/- 3.5 kPa, normal: paCO2 9.8 +/- 1.7 kPa), and 
      hyperthermia (susceptible: 40.6 +/- 2.0 degrees C, normal: 40.1 +/- 0.4 degrees C). There were no 
      significant differences in changes in clinical and laboratory variables between 
      groups. The dantrolene therapy regimen was effective in treating the MDMA-induced 
      metabolic crises. CONCLUSION: MDMA is not a classic trigger for the development 
      of malignant hyperthermia reactions in pigs. MDMA intoxication leads to severe, 
      long-lasting hyperthermia and hypermetabolism in both malignant 
      hyperthermia-susceptible and hyperthermia-normal pigs, with life-threatening 
      malignant hyperthermia-like symptoms which are responsive to supportive treatment 
      and dantrolene sodium suspension.
FAU - Schutte, Jan K
AU  - Schutte JK
AD  - Department of Anaesthesiology and Intensive Care Medicine, Hospital Cologne 
      Merheim, University of Witten/Herdecke, Cologne, Germany. 
      schuettej@kliniken-koeln.de
FAU - Schafer, Ute
AU  - Schafer U
FAU - Becker, Sandra
AU  - Becker S
FAU - Oldewurtel, Christiane
AU  - Oldewurtel C
FAU - Starosse, Alexander
AU  - Starosse A
FAU - Singler, Peter
AU  - Singler P
FAU - Richard, Annette
AU  - Richard A
FAU - Wappler, Frank
AU  - Wappler F
FAU - Gerbershagen, Mark U
AU  - Gerbershagen MU
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Anaesthesiol
JT  - European journal of anaesthesiology
JID - 8411711
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Uncoupling Protein 3)
RN  - F64QU97QCR (Dantrolene)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acidosis/metabolism
MH  - Animals
MH  - Dantrolene/metabolism/pharmacology
MH  - Fatty Acids, Nonesterified/metabolism
MH  - Fever/metabolism
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Hemodynamics
MH  - Homozygote
MH  - Hydrogen-Ion Concentration
MH  - Ion Channels/metabolism
MH  - Malignant Hyperthermia/*genetics
MH  - Mitochondrial Proteins/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Norepinephrine/metabolism
MH  - Swine
MH  - Time Factors
MH  - Uncoupling Protein 3
EDAT- 2012/11/10 06:00
MHDA- 2013/05/28 06:00
CRDT- 2012/11/10 06:00
PHST- 2012/11/10 06:00 [entrez]
PHST- 2012/11/10 06:00 [pubmed]
PHST- 2013/05/28 06:00 [medline]
AID - 10.1097/EJA.0b013e32835a1127 [doi]
PST - ppublish
SO  - Eur J Anaesthesiol. 2013 Jan;30(1):29-37. doi: 10.1097/EJA.0b013e32835a1127.