diacetylmonoxime and Tachycardia--Ventricular

The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 microg) into normal isolated perfused swine right ventricles (RVs) stained with 4-[beta-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 +/- 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 +/- 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 microg/ml, n = 3), and verapamil (2-4 microg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.

Topics: Aconitine; Action Potentials; Animals; Anti-Arrhythmia Agents; Bretylium Compounds; Computer Simulation; Diacetyl; Electrocardiography; Female; Male; Swine; Tachycardia, Ventricular; Ventricular Fibrillation; Verapamil

Tissue heterogeneities may play an important role in the mechanism of ventricular tachycardia (VT) and fibrillation (VF) and can lead to a complex spatial distribution of excitation frequencies. Here we used optical mapping and Fourier analysis to determine the distribution of excitation frequencies in >20 000 sites of fibrillating ventricular tissue. Our objective was to use such a distribution as a tool to quantify the degree of organization during VF. Fourteen episodes of VT/VF were induced via rapid pacing in 9 isolated, coronary perfused, and superfused sheep ventricular slabs (3x3 cm(2)). A dual-camera video-imaging system was used for simultaneous optical recordings from the entire epi- and endocardial surfaces. The local frequencies of excitation were determined at each pixel and displayed as dominant frequency (DF) maps. A typical DF map consisted of several (8.2+/-3.6) discrete areas (domains) with a uniform DF within each domain. The DFs in adjacent domains were often in 1:2, 3:4, or 4:5 ratios, which was shown to be a result of an intermittent Wenckebach-like conduction block at the domain boundaries. The domain patterns were relatively stable and could persist from several seconds to several minutes. The complexity in the organization of the domains, the number of domains, and the dispersion of frequencies increased with the rate of the arrhythmia. Domain patterns on the epicardial and endocardial surfaces were not correlated. Sustained epicardial or endocardial reentry was observed in only 3 episodes. Observed frequency patterns during VT/VF suggest that the underlying mechanism may be a sustained intramural reentrant source interacting with tissue heterogeneities.

Topics: Animals; Cardiac Pacing, Artificial; Diacetyl; Electrocardiography; Electrophysiology; Endocardium; Fourier Analysis; In Vitro Techniques; Neural Conduction; Optics and Photonics; Pericardium; Sheep; Tachycardia, Ventricular; Ventricular Fibrillation; Ventricular Function