Novel Antiarrhythmic and Cardioprotective Effects of Brilliant Blue G

Abstract

In this study, we investigated the effects of the purinergic P2X7 receptor antagonist brilliant blue G (BBG) on cardiac arrhythmia and myocardial injury induced by intravenously (i.v.) administered epinephrine in anesthetized rats. We also examined the possible involvement of beta-adrenergic receptors or cholinergic mechanisms in the effects of BBG. Sprague-Dawley rats were treated with epinephrine (10 μg/kg, i.v.). Brilliant blue G (100 mg/kg) was intraperitoneally (i.p.) administered thirty minutes prior to i.v. epinephrine. The effects of pretreatment with propranolol (2 mg/kg, i.p.) or atropine (2 mg/kg, i.v.) given prior to BBG and epinephrine were examined. The control group received saline. Moreover, the effects of only BBG on electrocardiogram (ECG) parameters were investigated. Results showed that compared with the saline control, BBG caused significant bradycardia (from 405.8 ± 1.18 to 239.4 ± 6.69 beats/min), increased RR interval (from 0.149 ± 0.002 to 0.254± 0.007 sec) and PR interval (from 0.051 ± 0.0008 to 0.059 ± 0.0004 sec), increased R wave amplitude (from 0.238 ± 0.019 to 0.548 ± 0.009 mv), and shortened QTc interval (from 0.169 ± 0.006 to 0.141 ± 0.003 sec) over 15 minutes after of BBG administration. BBG did not cause cardiac arrhythmia. Meanwhile, epinephrine produced significant bradycardia (209.8 ± 28.78 vs. 405.8 ± 1.18 beats/min), increased PR interval, prolonged the QRS complex, shortened QTc interval, decreased R wave amplitude and induced ventricular tachycardia. Brilliant blue G given prior to epinephrine increased heart rate and completely suppressed the epinephrine-induced ventricular arrhythmia. The inhibitory effect of BBG on the arrhythmia caused by epinephrine was prevented by atropine. In contrast the epinephrine induced arrhythmia was completely suppressed with propranolol and BBG. The histopathological study showed that epinephrine caused necrosis and apoptosis of cardiac muscle cells, degeneration of cardiac muscle fibers, and interstitial haemorrhages. These changes were markedly prevented by BBG alone, propranolol/BBG and to a less extent by atropine/BBG pretreatment. The study provided the first evidence for a cardioprotective and anti-arrhythmogenic actions for BBG against epinephrine-induced arrhythmia and myocardial damage, and suggested that cholinergic mechanisms are involved in its anti-arrhythmogenic action.