Intravenous administration of azumolene to reverse malignant hyperthermia in swine.
BACKGROUND
The efficacy of intravenous (IV) administration of azumolene (Az), an analogue 30-fold more soluble than dantrolene, on pigs susceptible to malignant hyperthermia (MH) is incompletely understood.


OBJECTIVE
To evaluate efficacy of Az on MH crisis in pigs.


METHODS
Eight normal (MHN) and 7 susceptible to MH (MHS) pigs (Landrace × Large White × Pietran).


METHODS
Prospective, laboratory trial. Hypermetabolic crisis was observed in MHS pigs, but not in MHN pigs, after a combined administration of inhaled halothane (1.5%) and IV injection of succinylcholine (SCh; 2.5 mg/kg). Susceptibility was confirmed using a caffeine and halothane contracture test. Az was administered 15 minutes after administration of SCh.


RESULTS
Respiratory acidosis (pH 7.16 ± 0.02; Pco(2) , 46.2 ± 9.1 mmHg, HCO(3) , 22.5 ± 2.3 mmol/L), fever (38.2 ± 1.1°C), cardiac arrhythmias, and muscle contracture were observed in MHS pigs. MHS pigs (n = 5) treated with Az (2 mg/kg IV) survived the crisis with attenuation of signs (pH 7.30 ± 0.10; Pco(2) , 36.3 ± 4.5 mmHg; HCO(3) , 22.9 ± 2.3 mmol/L) and recovery of normal muscle tone and cardiac rhythm.


CONCLUSIONS
Az represents a possible substitute for dantrolene to reverse MH crisis in susceptible pigs.
do Carmo
P L
PL
Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Zapata-Sudo
G
G
Trachez
M M
MM
Antunes
F
F
Guimarães
S E F
SE
Debom
R
R
Rizzi
M D R
MD
Sudo
R T
RT
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000627:therapeutic use*; D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D005260:Female; D005838:Genotype; D006221:Halothane / Q000009:adverse effects; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008305:Malignant Hyperthermia / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000662:veterinary*; D010080:Oxazoles / Q000008:administration & dosage* / Q000627:therapeutic use*; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000235:genetics
D018712:Analgesics, Non-Narcotic; D018685:Anesthetics, Inhalation; D007093:Imidazoles; D010080:Oxazoles; C061387:azumolene; D006221:Halothane