Rare genetic syndrome may hold key to cure for heat stroke

Gene found to control muscle contraction in 2 potentially fatal conditions

A genetic disorder that can cause a fatal rise in body temperature in some patients undergoing general anesthesia may hold the key to a cure for heat stroke, according to research published in the April 4 edition of the journal Cell. The findings further suggest that antioxidants, like those currently being tested to protect the lungs of cystic fibrosis patients, may also protect those genetically prone to suffer heat stroke.

According to the current study authors, all U.S. operating rooms should, but do not always, have a supply of a drug called dantrolene on hand, which causes muscles to relax by a unique mechanism. Dantrolene is a must in the rare cases where patients receiving general anesthesia unexpectedly go into whole-body muscle contractions as part of an inherited condition called malignant hyperthermia (MH). Occurring in one in about 10,000 adult patients undergoing general anesthesia, and more frequently in children, MH reactions alter the acid content of blood and tissues, increase heart rate, cause muscle rigidity and trigger a rapid rise in body temperature up to 112° F. Kidney failure and potentially fatal heart arrhythmias can result in the worse cases. MH received national news coverage recently because of the unfortunate case of an 18-year-old Florida high school senior, Stephanie Kuleba, whose death was apparently caused by a fatal reaction to anesthesia during corrective surgery.

Researchers are also interested in MH because it may be caused by the same biochemical pathways as heat stroke, a much more common condition that has caused more U.S. deaths than hurricanes, tornadoes, floods and earthquakes (8,000) together since 1979, according to the Centers for Disease Control and Prevention. Given the number of troops currently operating in deserts, the U.S. military has a keen interest in the work. For the first time, researchers at four universities and in the U.S. Army have provided strong evidence that the genetic and protein defects that cause MH also contribute to the development of heat stroke. They have also identified mechanisms by which both conditions may damage cells.

”Along with cardiac abnormalities, heat stroke is a major culprit in unexpected sudden deaths of otherwise fit, young athletes and soldiers,” said Robert T. Dirksen, Ph.D., associate professor of Pharmacology and Physiology at the University of Rochester Medical Center. “With a better knowledge of these mechanisms, we can begin to better diagnose and treat both disorders, and hopefully, save some lives,” said Dirksen, a co-author on the study.

The Perfect Switch