Novel, economical, electromechanical de-coupler that does not affect the electrical activity of the heart during ventricular fibrillation

Cardiac arrhythmias are undesirable electrical activity in the heart. Ventricular fibrillation (VF) is one such fatal cardiac arrhythmia and is characterized by the breakdown of organized electrical activity in the ventricular myocardium. However, little is known about VF, partially because it is difficult to study and understand an apparently disorganized activity. One method of studying VF is to analyze the epicardial signals using cardiac mapping techniques. One such form of cardiac mapping used to study complex aperiodic spatiotemporal activity is optical mapping. Optical mapping involves measurement and analysis of the fluorescence emitted by cardiac tissue stained with voltage sensitive drugs, which is representative of the cardiac action potential. The biggest limitation of cardiac mapping is motion artifact, which is due to the contraction of the cardiac muscle. The purpose of this study was to identify electro-mechanical decouplers that eliminate the mechanical activity of the heart without affecting the electrical activity. In this project, we used guinea pigs to test the electrical malignancy of drugs that eliminated mechanical activity of the heart in VF. Various concentrations of four drugs (Cytochalasin D, Latrunculin A, Latrunculin B and Mycalolide B) and one combination of drugs (Cytochalasin D and Latrunculin B) were tested in this study. An in vitro Langendorff set up was used to record mechanical activity after treatment with various concentrations of the pharmacological agents in 56 animals. VF was induced and 4 s of epicardial electrode data was acquired using a square array of 192 electrodes. Mechanical activity was measured using principle component analysis and electrical malignancy was measured using autocorrelation, frequency spectrum and spatial correlation analysis. Of all the drugs tested at various concentrations mechanical cessation of cardiac contraction was achieved only by the combination of Cytochalasin D and Latrunculin B at a concentration on 40 muM/l and 16 muM/l respectively. This novel combination of Cytochalasin D and Latrunculin B at the above mentioned concentrations did not have any significant effect on the organization of guinea pig VF and can be used as an electro-mechanical decoupler in optical mapping studies.