Antiarrhythmic Effects of Some Antioxidant Vitamins in Rats Injected with Epinephrine

Abstract

Since excessive amounts of catecholamines are known to produce arrhythmias and increase the plasma level of aminochrome, an oxidation product of catecholamines, we tested the hypothesis that antioxidants may reduce the formation of aminochrome and prevent the catecholamine-induced arrhythmias. For this purpose, Sprague-Dawley rats were pretreated orally, with vitamin A or vitamin C for 21 days, and their effects on ventricular arrhythmias induced by a bolus dose or cumulative doses of intravenous epinephrine were examined. Electrocardiogram recording of these animals revealed that pretreatment with either of these vitamins increased the time of onset and decreased the duration of the epinephrine-induced ventricular arrhythmias. Ventricular fibrillations due to high doses of epinephrine were also prevented by the antioxidant pretreatment. Although pretreatment with either vitamin A or vitamin C did not affect the basal malondialdehyde level in control animals, the increase in malondialdehyde level caused by epinephrine administration was significantly reduced by these agents. The elevated level of plasma aminochrome due to epinephrine was also decreased by vitamins A and C treatments. The results indicate that antioxidant may prevent catecholamine-induced arrhythmias by reducing the formation of aminochrome and thus may provide a new strategy for the management of stress-related heart disease.

Role of catecholamine oxidation in sudden cardiac death

“…Furthermore, high doses of epinephrine not only induced ventricular arrhythmias in healthy rats but were also found to increase the plasma concentration of aminochrome [61,62]. The epinephrine-induced changes in cardiac rhythm and plasma aminochrome levels were attenuated by pretreatment of animals with N-acetyl-L-cysteine, vitamin A, vitamin C, and vitamin E, which are known to exert antioxidant activity [61,62]. These observations support the view that ventricular arrhythmias because of excessive amounts of circulating catecholamines may induce cardiac arrhythmias because of their oxidation products such as adrenochrome and oxyradicals.…”

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

“…These pathways are known to have physiological ties to the pathogenesis of arrhythmias4041 and have been shown to be perturbed in vivo by drugs causing arrhythmias4243 (Table 2). Furthermore, nutrient supplementation targeted at these pathways has been found therapeutic in drug-induced arrhythmias4445 (Table 2). The remaining examples are presented in Supplementary Note 1.…”

Susceptibility of Diabetic Heart to Catecholamine-induced Arrhythmias is Independent of Contractile Dysfunction

“…These effects are mediated through the activation of β-adrenoceptors-cAMP-PKA system. Furthermore, in view of the occurrence of oxidative stress in diabetes (26,27,42), under conditions of increased catecholamines levels, there is an increase in the formation of catecholamine oxidation products, aminochromes, which have also been linked to arrhythmogenesis (2,3). Since the plasma levels of both Epi and NE were reduced in the 8-wk diabetic animals, there could also be a reduced production of aminochromes and therefore a reduced susceptibility to catecholamine-induced arrhythmias.…”

“…The overactivation of the sympathetic nervous system is invariably seen in subjects with high risk for sudden cardiac death and elevated circulating catecholamine levels are considered to result in lethal ventricular arrhythmias and subsequent sudden cardiac death (1)(2)(3)(4). Such arrhythomogenic effects of catecholamines are generally believed to occur, in part, by producing defects in intracellular Ca 2+ -handling (1-4).…”

“…Such arrhythomogenic effects of catecholamines are generally believed to occur, in part, by producing defects in intracellular Ca 2+ -handling (1-4). In addition, oxyradicals, which are known to generate oxidative stress, may play a critical role in the genesis of ventricular arrhythmias that may result in sudden cardiac death (1)(2)(3)(4). Both bradycardia and malignant ventricular arrhythmias occur in diabetic subjects (5,6).…”