Ritanserin attenuates the in vitro effects of the 5-HT2 receptor agonist DOI on skeletal muscles from malignant hyperthermia-susceptible patients.
OBJECTIVE
To study the in vitro effects of the serotonin2 (5-HT2) receptor agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and normal (MHN) patients following pretreatment with the 5-HT2 receptor antagonist ritanserin.


METHODS
Prospective study.


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


METHODS
41 patients undergoing in vitro contracture test for diagnosis of MH susceptibility.


METHODS
Skeletal muscle biopsies in adult patients were performed with a 3-in-1 nerve block with 40 ml prilocaine 1%. In children, general anesthesia was induced with 50 micrograms/kg alfentanil intravenously (i.v.) and 2 to 2.5 micrograms/kg propofol i.v. and maintained with a continuous infusion of propofol (< or = 150 micrograms/kg/min) and nitrous oxide (66%) in oxygen.


RESULTS
Patients were first classified as MHS or MHN by the in vitro contracture test according to the European MH protocol. Surplus muscle specimens of 21 MHS and 20 MHN patients were used in this study. At first, DOI was added to the organ bath at a concentration of 0.02 mM. In the second part of the study, muscle specimens were preincubated with ritanserin 0.01 mM for 10 minutes before DOI 0.02 mM was added to the bath. Muscle specimens from all patients developed contractures after administration of DOI. The onset of contractures was significantly faster in MHS muscles, and the magnitude of contracture was significantly greater than in MHN. The muscle twitch decreased significantly in both groups after DOI. After pretreatment with ritanserin, start of contracture was significantly delayed in MHS muscles. MHN muscles failed to develop contractures. The maximum level of contracture was significantly reduced in MHS. Muscle twitch decreased also in both MHS and MHN groups.


CONCLUSIONS
The findings may indicate that stimulation of 5-HT2 receptors is involved in MH induction. Furthermore, 5-HT2 receptor antagonists could possibly be effective in preventing MH. Additional studies are required to determine if administration of 5-HT2 receptor antagonists could be of additional value in the treatment or prevention of anesthetic-induced MH.
Wappler
F
F
Department of Anesthesiology, University-Hospital Eppendorf, Hamburg, Germany.
Scholz
J
J
Oppermann
S
S
von Richthofen
V
V
Steinfath
M
M
Schulte am Esch
J
J
D000293:Adolescent; D000328:Adult; D000662:Amphetamines / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis* / Q000503:physiopathology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D011446:Prospective Studies; D011985:Receptors, Serotonin / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine