a1-Adrenergic Receptor Subtype

Background. Recent advances in adrenergic pharmacology have made possible the identification of a1-adrenergic receptor subtypes using the specific blockers chloroethylcionidine and WB 4101. Methods and Results. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize ,B-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with lX i0` M phenylephrine. The incidence of abnormal automaticity was reduced to 0o by WB 4101 (which blocks phosphoinositide metabolic effects of a1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of a-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early afterdepolarizations was not seen in any experiment. Conclusions. Automatic arrhythmias induced by ael-adrenergic stimulation during simulated ischemia may be attributed to a specific al-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means 1991;83:2076-2082)