Background Ventricular tachycardia (VT) of focal endocardial and Purkinje origin occurs in humans. Pharmacological blockade of adrenoceptors on endocardial tissues may selectively prevent the induction of focal VT. We tested the hypothesis that alpha adrenoceptor blocker WB4101(WB), beta-1 receptor blocker metoprolol (Met), and beta-2 receptor blocker ICI 118,511(ICI) prevent the induction of focal ischemic VT and evaluated possible mechanisms.
Methods Fifty alpha chloralose anesthetized dogs with 1 to 4 hours of coronary artery occlusion (CAO) were involved. Twenty-three multipolar plunge electrodes were placed in and surrounding the risk zone of anterior descending coronary artery. three-dimensional activation mapping off-line helped to identify the origin of VT. If VT was reproducibly induced, WB (0.3 μg/kg, IV), Met (1 mg/kg), or ICI (0.2 mg/kg, IV) was given. The effects of blockers on delayed afterdepolarizations (DADs) and triggered activity (TA) recorded from endocardium and Purkinje tissue excised from the focal origin of VT were studied in vitro by standard microelectrode techniques.
Results Eleven dogs were given WB; two had VTs blocked with the same or more extrastimuli. Twelve dogs were received ICI; only 3 had VT blocked, which were no different compared to focal endocardial or Purkinje VT in dogs with saline treatment, of which 1 of 12 had apparent block (p = ns). However, 7 of 15 dogs given Met had focal VT blocked, which was different from the saline treated (p < .05). Of tissues at the origin of VT, excised and studied in vitro, all foci showed DADs and TA with ISO, which were were blocked by WB (10-7 M, in 2 of 6, p = ns), ICI (10-7 M, in 0 of 4, p = ns) and Met (10-7 M, in 6 of 8, p < .05 vs control).
Conclusions Pharmacological blockade of beta-1 adrenoceptor in acute ischemia selectively prevents induction of focal VT due to DADs and TA but alpha adrenoceptor and beta-2 receptor blockade does not.
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