A new study helps explain why some patients with malignant hyperthermia may suffer from excessive bleeding.
The findings suggest a mutation that causes malignant hyperthermia can disrupt calcium signaling in vascular smooth muscle cells, leading to bleeding abnormalities.
What’s more, researchers found that a drug clinically approved to treat muscle-related symptoms in malignant hyperthermia helped stop bleeding.
Rubén Lopez, of Basel University Hospital in Switzerland, and his colleagues conducted this research and reported their findings in Science Signaling.
Patients with malignant hyperthermia experience dangerously high fever and severe muscle contractions when exposed to general anesthesia.
Malignant hyperthermia is often caused by mutations in the RYR1 gene, which encodes a calcium channel in skeletal muscle called ryanodine receptor type 1 (RyR1).
For some patients with these mutations, malignant hyperthermia is accompanied by a mild bleeding disorder, but whether the 2 conditions are connected has not been clear.
Working in a mouse model of malignant hyperthermia, researchers found that vascular smooth muscle cells with mutated RyR1 displayed frequent spikes in calcium levels, known as calcium sparks. These sparks led to excessive vasodilation and prolonged bleeding.
Blocking the receptor with dantrolene, a drug used to treat malignant hyperthermia, helped reduce bleeding in the mice and in a single human patient, pointing to an unexpected benefit from the drug.
The findings suggest that mutations in RyR1, which is also found in other types of smooth muscle cells such as those in the bladder and uterus, may have a wider range of effects than previously thought.
