Genetically Engineered Pig Provides a Novel Tool to Study Life-Threatening Arrhythmias

A NYU Langone Medical Center research team has developed the first large animal model of an inherited arrhythmic syndrome. This animal model system should help heart scientists parse those mechanisms that establish the heart rhythm and conduct electrical impulses around the heart. This novel pig model can also help in the development of better treatments for inherited forms of life-threatening arrhythmias, which are a significant cause of sudden cardiac death.

These findings were published online in the Journal of Clinical Investigation. Already, this model system helped define what causes lethal arrhythmias in those patients with abnormal cardiac sodium channels. Normal conduction of electrical currents throughout the heart requires the normal functioning of these sodium channels. Disease-causing mutations in cardiac ion channels, which are technically referred to as “channelopathies,” can cause atrial and ventricular arrhythmias, progressive cardiac conduction disorders, and sudden cardiac death.

“By developing a genetically engineered pig sodium channelopathy model, we are now able to examine the mechanisms responsible for lethal arrhythmias in a human-like heart and investigate new therapies aimed at reducing sudden cardiac death,” said lead author David S. Park, MD, PhD, assistant professor, Leon H. Charney Division of Cardiology, Department of Medicine at NYU Langone.

Up to the present time, heart researchers have primarily used cultured heart cells and mouse models to study cardiac arrhythmias in humans. However, rodent hearts are no terrible good model systems for human heart diseases. However, “because of similarities of the pig heart to human hearts, research with the pig model will prove invaluable in gaining further insights into the mechanisms that underlie life-threatening arrhythmias,” said Glenn I. Fishman, MD, the study’s senior author, and Director of the Leon H. Charney Division of Cardiology at NYU Langone.

Both Drs. Fishman and Park envision a future where novel therapies, such as drugs that can enhance cardiac sodium channel expression or radiofrequency ablation procedures, can first be tested in the pig model before application to patients. “A better understanding of arrhythmia mechanisms should yield better therapies in the future,” said Dr. Park.