Malignant Hyperthermia (MH)

Malignant hyperthermia (MH) is an inherited disorder of skeletal muscle in which exposure to certain triggering factors can lead to a sudden and life-threatening hypermetabolic state. It is most commonly associated with a reaction to certain general anesthetics, but an episode can also be triggered by other factors, such as intense physical exertion, stress, mating, or illness. A horse with a genetic predisposition may show no clinical signs under normal conditions. However, when an episode is triggered, an uncontrolled increase in skeletal muscle metabolism occurs. Typical clinical signs include muscle rigidity, a rapid increase in body temperature, increased heart rate, cardiac arrhythmias, excessive sweating, and shallow breathing. At the same time, an increase in the concentration of carbon dioxide in the blood and the development of metabolic acidosis may occur. The condition can progress rapidly and, without timely intervention, may result in the death of the horse.

In American Paint Horses, Appaloosas, and Quarter Horses, malignant hyperthermia is associated with the c.7363C>G mutation in the RYR1 gene, which encodes ryanodine receptor 1. This protein forms a calcium channel in skeletal muscle that regulates the release of calcium ions from the sarcoplasmic reticulum and thus plays a fundamental role in muscle contraction. When an episode is triggered, excessive amounts of calcium are released into the muscle cells. The result is intense muscle activity and a sharp increase in metabolism, during which large amounts of heat are produced and other characteristic signs of malignant hyperthermia develop.

The predisposition to malignant hyperthermia is inherited in an autosomal dominant manner, meaning that a single copy of the mutated allele inherited from one parent is sufficient for its manifestation. In affected individuals, the risk of transmitting the condition to offspring is 50%.

The presence of the mutation does not mean that the horse will necessarily experience an acute episode during its lifetime. The development of an episode is significantly influenced by the presence of triggering factors. Genetic testing makes it possible to identify horses with a predisposition to malignant hyperthermia before clinical problems develop. Knowledge of the genotype is important not only for breeding planning, but also for veterinary care and planning general anesthesia, as it allows the veterinarian to be alerted to the increased risk and to adjust the choice of anesthetics and other procedures accordingly.

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References:

Aleman, M., Riehl, J., Aldridge, BM., LeCouteur, RA., Stott, JL., Pessah, IN.: Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia. Muscle Nerve 30:356–65, 2004. PubMed reference: 15318347