Ischemic ventricular arrhythmias: experimental models and their clinical relevance

In the United States, sudden cardiac death accounts for an estimated 300,000 to 350,000 cases each year, with 80,000 presenting as the first manifestation of a preexisting, sometimes unrecognized, coronary artery disease. Acute myocardial infarction (AMI)-induced ventricular fibrillation frequently occurs without warning, often leading to death within minutes in patients who do not receive prompt medical attention. Identification of patients at risk for AMI-induced lethal ventricular arrhythmias remains an unmet medical need. Recent studies suggest that a genetic predisposition may significantly contribute to the vulnerability of the ischemic myocardium to ventricular tachycardia/ventricular fibrillation. Numerous experimental models have been developed for the purpose of advancing our understanding of the mechanisms responsible for the development of cardiac arrhythmias in the setting of ischemia and with the aim of identifying antiarrhythmic therapies that could be of clinical benefit. While our understanding of the mechanisms underlying AMI-induced ventricular arrhythmias is coming into better focus, the risk stratification of patients with AMI remains a major challenge. This review briefly discusses our current state of knowledge regarding the mechanisms of ischemic ventricular arrhythmias and their temporal distribution as revealed by available experimental models, how these correlate with the clinical syndromes, as well as prospective prophylactic therapies for the prevention and treatment of ischemia-induced life-threatening arrhythmias.