Blockade of the Inward Rectifying Potassium Current Terminates Ventricular Fibrillation in the Guinea Pig Heart

• Published in: Journal of cardiovascular electrophysiology 2003-06, Vol.14 (6), p.621-631
• Main Authors: Warren, Mark, Guha, Prabal K., Berenfeld, Omer, Zaitsev, Alexey, Anumonwo, Justus M.B., Dhamoon, Amit S., Bagwe, Suveer, Taffet, Steven M., Jalife, José
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Electrophysiologic Techniques, Cardiac; fibrillatory conduction; Guinea Pigs; Heart Conduction System - cytology; Heart Conduction System - metabolism; Heart Conduction System - physiopathology; Heart Ventricles - cytology; Heart Ventricles - metabolism; Heart Ventricles - physiopathology; Kir2.1; Kir2.3; Membrane Potentials - physiology; Models, Cardiovascular; Myocytes, Cardiac - metabolism; optical mapping; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying - administration & dosage; Potassium Channels, Inwardly Rectifying - metabolism; rotors; ventricular fibrillation; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - physiopathology
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1046/j.1540-8167.2003.03006.x

Introduction: Stable high‐frequency rotors sustain ventricular fibrillation (VF) in the guinea pig heart. We surmised that rotor stabilization in the left ventricle (LV) and fibrillatory conduction toward the right ventricle (RV) result from chamber‐specific differences in functional expression of inward rectifier (Kir2.x) channels and unequal IK1 rectification in LV and RV myocytes. Accordingly, selective blockade of IK1 during VF should terminate VF. Methods and Results: Relative mRNA levels of Kir2.x channels were measured in LV and RV. In addition, LV (n = 21) and RV (n = 20) myocytes were superfused with BaCl2 (5–50 μmol/L) to study the effects on IK1. Potentiometric dye‐fluorescence movies of VF were obtained in the presence of Ba2+ (0–50 μmol/L) in 23 Langendorff‐perfused hearts. Dominant frequencies (DFs) were determined by spectral analysis, and singularity points were counted in phase maps to assess VF organization. mRNA levels for Kir2.1 and Kir2.3 were significantly larger in LV than RV. Concurrently, outward IK1 was significantly larger in LV than RV myocytes. Ba2+ decreased IK1 in a dose‐dependent manner (LV change > RV change). In baseline control VF, the fastest DF domain (28–40 Hz) was located on the anterior LV wall and a sharp LV‐to‐RV frequency gradient of 21.2 ± 4.3 Hz was present. Ba2+ significantly decreased both LV frequency and gradient, and it terminated VF in a dose‐dependent manner. At 50 μmol/L, Ba2+ decreased the average number of wavebreaks ( 1.7 ± 0.9 to 0.8 ± 0.6 SP/sec · pixel, P < 0.05 ) and then terminated VF. Conclusion: The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics. (J Cardiovasc Electrophysiol, Vol. 14, pp. 621‐631, June 2003)