Dantrolene: From Better Bacon to a Treatment for Ventricular Fibrillation
The "porcine stress syndrome" is a major cause of poor meat quality and death in the pork industry. It is known to be more prevalent in some pig strains than others,1 and susceptible animals can be identified by challenge with halothane, which results in striking elevation in body temperature. This scenario parallels the clinical entity of familial malignant hyperthermia upon exposure to general anesthetics, which was one of the earliest recognized human pharmacogenetic syndromes. We now know that affected pigs and people share the same molecular mechanism, mutations in the sarcoplasmic reticulum (SR) calcium release channel of skeletal muscle encoded by RYR1.2,3 In the pig world, selective breeding programs have been used to develop strains resistant to malignant hyperthermia. In humans, malignant hyperthermia is an anesthetic emergency and is treated by immediate intravenous administration of dantrolene which is effective and thought to be safe. Chronic oral dantrolene is also approved to treat severe muscle spasticity, and in this setting the limiting toxicity is hepatitis which can be fulminant and fatal in up to 1% of exposed subjects.
- Received December 21, 2013.
- Accepted December 26, 2013.