Inhibition of Ischemia-induced Arrhythmias by Blocking Mitochondrial Inner Membrane Ion Channels

This invention describes a method for preventing and/or terminating ischemia-related arrhythmias by targeting the mechanism responsible for the electrical instability occurring during an ischemic episode or upon reperfusion of the heart. Inhibition of a mitochondrial inner membrane anion channel, either directly or indirectly through the mitochondrial benzodiazepine receptor, prevents or reverses mitochondrial depolarization under metabolic stress. Reduced mitochondrial depolarization leads to reduced activation of surface membrane ATP-sensitive potassium channels, and consequently to reduced spatial dispersion of action potential repolarization and regional electrical inexcitability across the ventricle. The net effects of this treatment are to prevent initiation of fatal arrhythmias and to preserve cardiac function. This treatment further offers the possibility of therapeutic intervention prior to the development of potentially fatal post ischemic arrythmias. Background Coronary heart disease (CHD) is the number one killer in the United States, each year claiming more lives than the next five causes of death combined. In the majority of cases death results from an abrupt loss of heart function (Sudden Cardiac Death) associated with ischemia-induced ventricular fibrillation (VF). Despite the prevalence of ischemia-induced VF no treatment apart from electrical defibrillation is presently available. Electrical defibrillation can only be applied after the potentially fatal arrhythmia has begun and, in many cases, is ineffective at restoring normal electrical function. Accordingly, there is an urgent need for alternative approaches to prevent and treat ischemia-induced arrythmias. Description (Set) Proposed Use (Set) CHD is the number one cause of death in the US at an estimated cost of $384 billion for the healthcare system in 2004 alone. The American Heart Association estimates that about 335,000 people a year die of sudden cardiac death. This technology would provide the first specific drug treatment for preventing or reversing ischemia-related cardiac arrhythmias responsible for the majority of such deaths.

Inventor(s): O'Rourke, Brian

Type of Offer: Licensing

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