In vivo and in vitro responses to magnesium sulphate in porcine malignant hyperthermia.

Magnesium sulphate has previously been shown therapeutic in porcine malignant hyperthermia. It was given intravenously in doses of 99 mg. kg -~ before and 277 mgkg -~ after an episode of malignant hyperthermia had been produced by halothane 1.5 per cent, in agroup of four malignant hyperthermia susceptible swine. Two groups of four additional MH susceptible and MH resistant swine received a constanl infusion of magnesium sulphate 10 mg. kg -~ until approximately 95 per cent depression of foretoe twitch was produced. Four hyperthermia susceptible controls received saline infusions. All were then immediately challenged with succinylcholine 2 rag. kg -t and halothane 1.5 per cent. Muscle strips from three other malignant hyperthermia swine were exposed in vitro to magnesium sulphate with and without halothane, and response of twitch tension and contracture were measured. The malignant hyperthermia response to halothane 1.5 per cent was attenuated but not prevented by pretreatment with magnesium sulphate. It did not appear to be therapeutic in this group. Depression of toe twitch by magnesium sulphate was similar in MH susceptible and MH resistant pigs. Pretreatment wilh magnesium sulphate markedly attentuated the response to a succinylcholine-halothane challenge in MH susceptible pigs. In vitro magnesium sulphate depressed twitch and halothane coutracture responses. We conclude that magnesium sulphate is partially prophylactic for the malignant hyperthermia challenge. The mechanism of this response is likely secondary to calcium ion antagonism at multiple sites. The muscle relaxant reponse to magnesium sulphate cannot be used as a diagnostic test for porcine malignant hyperthermia. INTRAVENOUS MAGNESIUM ION has been s h o w n to be of therapeut ic benefit in es tabl ished porcine mal ignant hyper thermia (MH).I'2 The aetiology of MH is unknown but may involve abnormal calcium ion metabol i sm in skeletal muscle. 3 Magnes ium ion can antagonize physiological even t s mediated by calcium ion. This s tudy eva lua tes the effect of in t ravenous m a g n e s i u m sulphate on the response to malignant hyperthermia challenge by anaes thes ia and on the already es tabl ished MH syndrome . Response o f foretoe twitch tension depress ion to in t ravenous magnes ium sulphate in malignant hyper thermia suscept ib le (MHS) and malignant hyper the rmia res is tant (MHR) swine was evaluated. The effects of increased magnes i um sulphate concentration on basal twitch and cont rac ture response to halothane of muscle strips obtained from malignant hyper the rmia suscept ible animals were also measured in vilro. METHODS AND MATERIALS The exper imcnta l animals were pure-bred PoE.H. Flewellen, M.D., Assitant Professor; T.E. Nelson, Ph.D., Assistant Professor, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, 77550 U.S.A. Supported in part by NIH Grant 23875-01. Canad. Anaesth. Soc. J., vol. 27, no. 4, July 1980 land China mal ignant hyper the rmia suscept ib le (MHS) or Hampsh i re mal ignant hyper the rmia res is tant (MHR) swine. Susceptibil i ty was established by first subject ing each animal to in vi tro caffeine-halothane cont rac ture testing. 4 Anaesthesia was induced and mainta ined in all experiments with th iopentone 2.5 per cent , in a dose sufficient to allow orotracheal intubat ion and to obtund limb m o v e m e n t when halothane was not being added. Oxygen 4 l i tres, min t was provided through a semi-closed circle carbon dioxide absorption breathing circuit. Ventilation was assisted or controlled with a Bird Mark 4A ventilator. Peak expired carbon dioxide and halothane concent ra t ions were moni tored by con t inuous sampling from the exhala t ion hose . Rectal t empera ture was also moni tored continuously. Fluids and th iopentone were adminis tered through an ear vein catheter . Arte.rial p ressure was measu red by t r ansduce r and recorded f rom an ear artery. Magnes ium sulphate was administered through an anter ior vena cava ca the ter and blood was sampled for magnes ium from the arterial line. Foretoe twitch tens ion (indirectly s t imulated) was t ransduced and recorded as previously descr ibed, s Rest ing tens ion was 100 g. Lacta ted Ringer ' s solution 5 ml . kg t was infused during all exper imenta l procedures .