Simulação em LabHEART de fatores que causam arritmia ventricular

Abstract

The action potential duration (APD) vs frequency relationship is a clear indicative of a healthy cardiac cell. Heart failure myocytes exhibit a characteristical flat response as the frequency increases. Mathematical models allow us to study the ionic components responsabile for tha behavior. We customized the LabHEART model by altering the ionic currents formulations to reproduce the experimental data of control and pathological conditions from dog ventricular myocytes. Compared with control data, the inward rectifier K⁺ current (I _K1) was decreased, the maximum conductance of the rapid component of the delayed rectifier K⁺ current (I _Kr) was increased, the activation kinetics was slowed and the rectification property was augmented. The slow component of the delayed rectifier K⁺ current (I _Ks) was increased in magnitude and activation shifted to less positive voltages. L-type Ca²⁺ current (I _Ca) was modified to produce a smaller, more rapidly inactivating current. Finally, a simplified form of intracellular calcium dynamics was adopted. In our simulations APD increased from 274.3 + ou - 16.6 ms (control) to 405.2 + ou - 24.0 ms (pathological) for a range frequencies of 0.1 to 2 Hz. Calcium transient amplitude was severely decreased in the pathological case. These results show the importance of in silico experiments to study cardiac arrythmias and the search of new pharmacological targets.