Drug Could Help Preserve Brain Function After Cardiac Arrest

An experimental drug that targets a brain system that controls inflammation might help preserve neurological function in people who survive sudden cardiac arrest, new research suggests.

Survival rates for sudden cardiac arrest are low, but recent medical advancements have improved the chances for recovery. Many people who do survive suffer a range of disorders that relate to neurological deficits caused by loss of blood flow to the brain when their heart stops.

The researchers, led by a team at Ohio State University, believe these neurological problems might relate to inflammation and brain-cell death. The study revealed how the brain is damaged during cardiac arrest, as well as how a drug might counter those effects.

The scientists identified in a mouse model how the loss of blood in the brain sets off a process that attracts inflammatory compounds and kills brain cells. The study showed that these damaging effects were associated with alteration of the cholinergic system – an area of the brain that sends signals using the neurotransmitter acetylcholine to regulate inflammation.

Mice that were treated with an experimental drug called GTS-21, which activates acetylcholine, had lower levels of inflammatory chemicals and reduced damage to brain cells in the days following a surgically induced cardiac arrest and subsequent resuscitation.

“This is a drug that has been used safely in humans in clinical trials, so we think our findings have significant clinical potential,” said Courtney DeVries, professor of neuroscience and psychology at Ohio State University and senior author of the study. “Another very important aspect of the study is that the drug was not given until 24 hours after resuscitation, and yet it was successful at reversing inflammatory effects in the brain. So there would be a large therapeutic window of time if this could eventually be used clinically.”

The research is published in the March 2 issue of The Journal of Neuroscience.

Cardiac arrest is not the same as a heart attack, which occurs when blood flow to the heart is interrupted. In sudden cardiac arrest, the heart’s electrical system malfunctions and blood flow stops altogether. The American Heart Association estimates that fewer than 8 percent of people who suffer cardiac arrest in a home or community setting will survive, and that brain damage can occur within four to six minutes after the heart has stopped. Lasting effects of this brain damage can include physiological problems as well as memory loss and increased anxiety and depression.

In this study, the researchers surgically induced cardiac arrest in groups of anesthetized mice and then revived them eight minutes later using cardiopulmonary resuscitation. The scientists then analyzed brain tissue in mice three and seven days after the heart stoppage. Some mice received the drug beginning 24 hours after resuscitation, and some did not.