Activation of β1-adrenoceptors may not be involved in arrhythmogenesis in ischemic heart disease

Adriana Adameová ,Vijayan Elimban,Sukhwinder K Bhullar ,Naranjan S Dhalla

doi:10.31083/j.rcm.2018.03.3181

Abstract

Although ischemic heart disease is invariably associated with marked activation of sympathetic nervous system, elevated levels of circulating catecholamines and lethal ventricular arrhythmias, the mechanisms of arrhythmogenesis due to myocardial ischemia are not fully understood. Since catecholamines are known to produce stimulatory effects in the heart mainly by acting on β1-adrenoceptors, this study was undertaken to test the involvement of these receptors in the development of arrhythmias due to myocardial infarction (MI) induced upon occluding the left coronary artery in rats for a period of 2 h. The animals were treated with or without atenolol (20 mg/kg; daily), a selective β1-adrenoceptors blocker, for 14 days before inducing MI. No alterations in the number of MIinduced episodes and incidence or duration of different types of arrhythmias were observed. In fact, the incidence of trigemines and reversible ventricular fibrillation due to MI were significantly increased in the atenolol-treated animals. These observations support the view that the activation of β;1-adrenoceptors may not be exclusively involved in the development of arrhythmias during the occurrence of ischemic heart disease and other mechanisms can underlie the electric instability of such damaged heart.

Highlights

It is well known that the sympathetic nervous system (SNS) is activated under a wide variety of stressful conditions including ischemic heart disease (Dhalla et al, 1993; Randhawa et al, 2016)
No significant differences in the onset of myocardial infarction (MI)-induced arrhythmias including ventricular premature beats (VPB), ventricular tachycardia (VT) and total VF (tVF) as well as arrhythmia score were observed in the control and atenolol treated animals (Fig. 3A and B)
Since the coronary occlusion has been observed to be associated with marked increase in the plasma levels of both catecholamines and angiotensin II as well as various oxidants in the heart (Babick et al, 2013; Dhalla et al, 2000a; Shao et al, 1996), it has been suggested that the MI-induced cardiac effects, hemodynamic changes and arrhythmias are elicitepd by neurohormonal activation and oxidative stress (Dhalla et al, Onset (s)

Summary

Introduction

It is well known that the sympathetic nervous system (SNS) is activated under a wide variety of stressful conditions including ischemic heart disease (Dhalla et al, 1993; Randhawa et al, 2016). Since catecholamines are known to produce positive inotropic and chronotropic actions on the heart by acting on β -adrenoceptors, resulting in increasing cyclic AMP and elevating the level of intracellular Ca2+ concentration (Adameova et al., 2009), it is generally considered that arrhythmias due to high levels of catecholamines in ischemic heart disease is a consequence of activation of β -adrenoceptors in the myocardium This view is supported by clinical observations that long-term administration of certain β -adrenoceptors blockers improves survival of patients with myocardial infarction (MI), most probably by preventing ventricular fibrillation (Freemantle et al, 1999). In view of such controversial reports, the present study was undertaken to examine the effects of long term pretreatment with high doses of a selective β -adrenoceptors blocker, atenolol, on different types of arrhythmias induced upon occluding the coronary artery in anesthetized rats

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Conclusion