Effect of isoprenaline chronic stimulation on APD restitution and ventricular arrhythmogenesis

Isoprenaline (ISO) acts through β-adrenergic receptors to increase the intracellular Ca(2+), which has effects on action potential duration (APD) restitution and arrhythmogenesis. Thus, we investigated the effect of chronic stimulation with isoprenaline on APD restitution and ventricular tachyarrhythmias (VA) in the rabbit heart.

Rabbits were randomly selected to receive an injection of isoprenaline (ISO group) or an equal volume of 0.9% saline (CTL group). The S(1)-S(2) protocol (n=15) and S(1) dynamic pacing (n=15) were performed to construct APD restitution and to induce APD alternans or arrhythmia in 10 sites of Langendorff-perfused hearts. Compared with the same sites in the control group, long-term ISO administration (7 days) shortened the APD(90) and the effective refractory period (ERP), and greatly increased the spatial dispersion of APD and ERP (p<0.01). Compared to CTL group, the APD restitution curves were significantly changed (p<0.01) and showed increased spacial dispersion of maximal slope (S(max)) among each site in the ISO group (p<0.05). In induction of VA and APD alternans, the threshold of VA and alternans was both decreased in each site of the ISO group.

Chronic stimulation with ISO facilitated VA, possibly through the increased spatial dispersion of APD restitution.