We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Blockade of the Inward Rectifying Potassium Current Terminates Ventricular Fibrillation in the Guinea Pig Heart.
- Authors
Warren, Mark; Guha, Prabal K.; Berenfeld, Omer; Zaitsev, Alexey; Anumonwo, Justus M.B.; Dhamoon, Amit S.; Bagwe, Suveer; Taffet, Steven M.; Jalife, José
- Abstract
I[sub K1] Blockade and VF Dynamics. 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 I[sub K1] rectification in LV and RV myocytes. Accordingly, selective blockade of I[sub K1] 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 BaCl[sub 2] (5–50 μmol/L) to study the effects on I[sub K1]. Potentiometric dye-fluorescence movies of VF were obtained in the presence of Ba[sup 2+] (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 I[sub K1] was significantly larger in LV than RV myocytes. Ba[sup 2+] decreased I[sub K1] 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. Ba[sup 2+] significantly decreased both LV frequency and gradient, and it terminated VF in a dose-dependent manner. At 50 μmol/L, Ba[sup 2+] 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 I[sub K1] plays an important role in rotor stabilization and VF dynamics. (J Cardiovasc Electrophysiol, Vol. 14, pp. 621-631, June 2003).
- Subjects
VENTRICULAR fibrillation; POTASSIUM channels; HEART; GUINEA pigs
- Publication
Journal of Cardiovascular Electrophysiology, 2003, Vol 14, Issue 6, p621
- ISSN
1045-3873
- Publication type
Article
- DOI
10.1046/j.1540-8167.2003.03006.x