Xenon, currently under investigation for use in humans, offers some advantages over routinely used gases, but whether it can trigger malignant hyperthermia has not been previously investigated. Froeba et al. tested nine pigs for the presence of the RYR1 arg-615-cys mutation by restriction analysis on genomic DNA. This genetic mutation is associated with an abnormally high release of calcium in the skeletal muscle. The nine pigs in which this mutation was verified were premedicated with intramuscular azaperone, and anesthesia was induced with pentobarbital sodium. Ventilation was performed with a standard semiclosed circuit anesthesia machine modified to provide for xenon application. Systemic and pulmonary artery pressures, as well as central venous pressure, were continuously recorded using calibrated pressure transducers aligned at the right atrial level. Cardiac output was measured using thermodilution, and mass spectrometry was used to measure concentrations of xenon, oxygen, and nitrogen in the inspiratory limb of the ventilator cycle.
After instrumentation, animals were allowed to recover for 1 h. After control data were obtained, heating pads were switched off and xenon was administered. Blood sampling and cardiac output measurement were repeated every 10 min for 2 h, at which point xenon was discontinued and allowed to wash out over a period of 30 min. After obtaining a second set of control data, the investigators connected the pigs to a second anesthesia machine and, as a positive control, administered halothane, followed 15 min later by succinylcholine. Blood sampling and cardiac output measurements were repeated every 10 min until death. Exposure to xenon did not induce changes in metabolic or hemodynamic parameters and produced no elevations in plasma catecholamine levels indicative of malignant hyperthermia. However, within 20 min of halothane and succinylcholine administration, fatal malignant hyperthermia episodes were initiated in all study animals. These studies suggest that xenon may not be a triggering agent of malignant hyperthermia.