26 Dec Pig Model Allows Further Study Of Sudden Cardiac Death Syndromes
MedicalResearch.com Interview with:
Dr. Glenn I. Fishman MD
Professor; William Goldring Professor of Medicine
Vice Chair Research Dept of Medicine
Director of the Leon H. Charney Division of Cardiology
Medical Research: What is the background for this study? What are the main findings?
Dr. Fishman: Sudden cardiac arrest (SCA) due to life-threatening ventricular arrhythmias is one of the leading causes of death in the US. Conditions that predispose to SCA can be acquired, as in atherosclerotic coronary artery disease, or inherited in the form of mutated cardiac ion channels, i.e. ion channelopathies. Mutations in the SCN5A cardiac sodium channel gene have been linked to progressive cardiac conduction disorders as well as atrial and ventricular arrhythmias. Understanding the mechanistic basis for lethal arrhythmias in cardiac sodium channelopathy patients has been limited in part due to the lack of adequate model systems that replicate human physiology. To address this limitation, we have developed the first genetically modified porcine model of an inherited channelopathy. A mutation in the SCN5A gene first identified in a child with the arrhythmic condition Brugada syndrome was introduced into the pig genome. Mutant pig hearts displayed conduction abnormalities and ventricular fibrillation bearing striking resemblance to the human condition.
Medical Research: What should clinicians and patients take away from your report?
Dr. Fishman: By developing a genetically engineered porcine 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.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Fishman: We envision two immediate uses for the SCN5A pig model:
1) Evaluate how proposed triggers for Sudden cardiac arrest in sodium channelopathy patients, such as fever, vagal tone, and cardiac fibrosis, modify the arrhythmic substrate in mutant hearts, and
2) Novel therapies, such as drugs that can enhance cardiac sodium channel expression or radiofrequency ablation procedures, can first be tested in the SCN5A pig model before application to patients.
David S. Park, Marina Cerrone, Gregory Morley, Carolina Vasquez, Steven Fowler, Nian Liu, Scott A. Bernstein, Fang-Yu Liu, Jie Zhang, Christopher S. Rogers, Silvia G. Priori, Larry A. Chinitz, Glenn I. Fishman. Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI76919