2‐APB attenuates thromboxane A2‐induced arrhythmias

Abstract

Previous work in our lab has shown that left atrial injections of a thromboxane A2 (TxA2) mimetic, U46619, induces accelerated idioventricular rhythm in the anesthetized rabbit. Furthermore, we have shown that these arrhythmias occurred without significant changes in coronary blood flow or activation of autonomic reflexes. Therefore, we hypothesize that TxA2 may induce arrhythmias by stimulating cardiac myocytes directly via activation of intracellular calcium release. Three groups of anesthetized animals were pretreated with 1 of 3 increasing doses, 0.05 mg (n = 5), 0.5 mg (n = 7), or 5 mg (n = 6), of an inhibitor of IP3 mediated calcium release, 2-aminoethoxydiphenyl borate (2-APB), prior to left atrial injections of U46619 at 10, 20, and 30 μg doses. The average total number of arrhythmias induced in each animal following the 30 μg U46619 injection was 338, 0, and 11, at the 0.05 mg, 0.5 mg, and 5 mg doses of 2-APB, respectively. Furthermore, the total number of animals that exhibited arrhythmias was reduced in the higher doses (0.5 mg and 5 mg) of 2-APB. Two animals showed t-wave changes following administration of 2-APB (0.5 mg) prior to U46619 injection, and arrhythmias occurred in 1 animal post-injection of 2-APB (5 mg). These animals were not included in further data analysis. These data indicate that 2-APB does attenuate TxA2-induced arrhythmias.