Session P7C.4

Influence of 1B Ischemic Ventricular Tissue on the Automaticity of Purkinje Fibers: A Simulation Study

E Ramírez*, J Sáiz, B Trénor, JM Ferrero,
G Moltó, V Hernández

Universidad Politécnica de Valencia
Valencia, Spain

Acute myocardial ischemia is considered an important cause of sudden cardiac death. Sudden cardiac death is primarily due to ischemia-induced ventricular arrhythmias, in particular to ventricular fibrillation (VF). During acute ischemia, ventricular arrhythmias occur in two different phases. Firstly, arrhythmias take place during phase 1A, between 2 and 15 minutes after coronary occlusion. After an interval relatively free of arrhythmias, a second phase of arrhythmic events is observed (referred as 1B phase), between 15 and 60 minutes after the onset of ischemia. It is known that arrhythmias originating in Purkinje fibers may occur in this phase of ischemia.
The aim of this study was to investigate the influence of 1B ischemic ventricular tissue on the automaticity of Purkinje cells and its role in ectopic activity that could provoke arrhythmias.
We simulated the electrical activity of a 1D Purkinje fiber of 1.5 cm coupled to a regionally 1B ischemic ventricular fiber of 3 cm through a Purkinje-muscle resistance (Rpvj). The ventricular fiber comprised a 1B ischemic zone, a border zone and a normal zone (from left to right) of 1 cm each. To simulate ischemia, we altered several electrophysiological parameters of the Luo-Rudy action potential model (Lrd00) as proposed by Pollard and coworkers. These parameters were linearly varied in the border zone from the normal values in the normal tissue to the ischemic values in the central ischemic zone.
We stimulated the left edge of the Purkinje fiber with one current pulse. As a consequence, Purkinje cells autogenerated 10 pulses, which propagated through the whole fiber. The last autogenerated action potential was considered for analysis. Our results show that in the absence of myocardial ischemia in the ventricular fiber, the basic cycle length (BCL) of the autogenerated pulse of Purkinje fiber yielded 1659 ms. However, under ischemic conditions ([K+]o = 12 mmol/L, Rpvj = 16 ohm.cm2, Rendo = 5 ohm.cm2) the BCL was reduced to 1518 ms. This change in BCL represented a decrease of 8.5%, enhancing the automaticity of Purkinje cells. Another observed phenomenon was the fact that the site of generation of the autogenerated pulse along the Purkinje fiber changed with the severity of ischemia. In the absence of ischemia, the autogenerated pulse was initiated in the left edge of the Purkinje fiber. With increasing [K+]o to 12 mmol/L in 1B ischemic ventricular tissue, the autogenerated pulse was initiated closer to Purkinje-muscle junction (PMJ). Then the elicited action potential propagated in both directions, forward to ventricular cells and backward to the rest of Purkinje cells.
In conclusion, our study shows that 1B ischemic ventricular tissue enhances automaticity of Purkinje fibers and could have an important role on the generation of ectopic action potentials near the Purkinje-muscle junctions. This phenomenon may be involved in the generation of ectopic activity and cardiac arrhythmias.

(Abstract Control Number: 137)