(Credit: Simon Migaj/Unsplash)
A powerful new computer model replicates biological activity in the heart that precedes sudden cardiac arrest. The advance will help researchers better study the rare but often fatal sequence of events.
Sudden cardiac arrest occurs when an arrhythmia—an irregular heartbeat—disrupts normal electrical activity in the heart and stops it from pumping.
“For the first time, we have come up with a method for relating how distressed molecular mechanisms in heart disease determine the probability of arrhythmias in cardiac tissue,” says Raimond L. Winslow, professor of biomedical engineering at Johns Hopkins University.
Sudden cardiac arrest can occur in people who seem healthy and…is usually fatal—often within minutes.
“The importance of this is that we can now quantify precisely how these dysfunctions drive and influence the likelihood of arrhythmias. That is to say, we now have a way of identifying the most important controlling molecular factors associated with these arrhythmias.”
Sudden cardiac arrest can occur in people who seem healthy and have no known risk factors, the National Institutes of Health says. It is usually fatal—often within minutes—without rapid medical intervention. The arrhythmias linked to sudden cardiac death are rare, however, making it difficult to study how they occur and might be prevented.
As reported in PLOS Computational Biology, the digital model offers important clues that could lead to the identification of treatment targets for drug makers.
“It could lead to better drugs that target the right mechanisms,” says Winslow, senior author of the study. “If you can find a molecule that blocks this particular action, then doing so will significantly reduce the probability of an arrhythmia, whereas other manipulations will have comparatively negligible effects.”
Researchers wanted to learn what led to arrhythmia at three biological levels: in the heart tissue as a whole, within individual heart cells, and within the molecules that make up the cells, including small proteins called ion channels that control the movement of calcium in the heart.
“Calcium is an important player in the functioning of a heart cell,” says Mark Walker, the study’s lead author. “There are a lot of interesting questions about how the handling of calcium in heart cells can sort-of go haywire.”
Walker and colleagues chose to focus on one question: When heart cells possess too much calcium, which can happen in heart disease patients, how does this overload of calcium trigger an arrhythmia?
They discovered that overloaded heart cells expel excess calcium, and, in doing so, generate an electrical signal. If, by chance, enough of these signals come at the same time, arrhythmia can start.