How does β-adrenergic signalling affect the transitions from ventricular tachycardia to ventricular fibrillation?

Ventricular tachycardia (VT) and fibrillation (VF) are the most lethal cardiac arrhythmias. The degeneration of VT into VF is associated with the breakup of a spiral wave of the action potential in cardiac tissue. -Adrenergic (AR) signalling potentiates the L-type Ca current (I-CaL) faster than the slow delayed rectifier potassium current (I-Ks), which transiently prolongs the action potential duration (APD) and promotes early after depolarizations. In this study, we aimed at investigating how AR signalling affects the transition from VT to VF. We used a physiologically detailed computer model of the rabbit ventricular myocyte in a two-dimensional tissue to determine how spiral waves respond to AR activation following administration of isoproterenol. A simplified mathematical model was also used to investigate the underlying dynamics. We found that the spatiotemporal behaviour of spiral waves strongly depends on the kinetics of AR activation. When AR activation is rapid, a stable spiral wave turns into small fragments and its electrocardiogram reveals the transition from VT to VF. This is due to the transiently steepened APD restitution induced by the faster activation of I-CaL vs. I-Ks upon sudden AR activation. The spiral wave may also disappear if its transient wavelength is too large to be supported by the tissue size upon sudden strong AR activation that prolongs APD transiently. When AR activation is gradual, a stable spiral wave remains such, because of more limited increase in both APD and slope of APD restitution due to more contemporaneous I-CaL and I-Ks activation. Changes in APD restitution during AR activation revealed a novel transient spiral wave dynamics; this spatiotemporal characteristic strongly depends on the protocol of isoproterenol application.