Intravenous administration of azumolene to reverse malignant hyperthermia in swine

• Published in: Journal of veterinary internal medicine 2010-09, Vol.24 (5), p.1224-1228
• Main Authors: Carmo, P.L. do, Zapata-Sudo, G, Trachez, M.M, Antunes, F, Guimaraes, S.E.F, Debom, R, Rizzi, M.D.R, Sudo, R.T
• Format: Article
• Language: English
• Subjects: acidosis; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - therapeutic use; Anesthesia; Anesthetics, Inhalation - adverse effects; Animals; arrhythmia; caffeine; Calcium; contracture; Female; fever; Genotype; halothane; Halothane - adverse effects; Imidazoles - administration & dosage; Imidazoles - therapeutic use; intravenous injection; landraces; Large White; Male; malignant hyperthermia; Malignant Hyperthermia - drug therapy; Malignant Hyperthermia - etiology; Malignant Hyperthermia - genetics; Malignant Hyperthermia - veterinary; medicine; muscles; Oxazoles - administration & dosage; Oxazoles - therapeutic use; Pig; Skeletal Muscle; suxamethonium; Swine; Swine Diseases - drug therapy; Swine Diseases - genetics
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/j.1939-1676.2010.0556.x

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. Animals: 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; Pco2, 46.2 +/- 9.1 mmHg, HCO3, 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; Pco2, 36.3 +/- 4.5 mmHg; HCO3, 22.9 +/- 2.3 mmol/L) and recovery of normal muscle tone and cardiac rhythm. Conclusions and Clinical Importance: Az represents a possible substitute for dantrolene to reverse MH crisis in susceptible pigs.