Therapeutical Options to Influence the Autonomic Nervous System

Abstract

The evidence of the predictive value of autonomic markers has generated a growing interest for interventions able to influence autonomic control of heart rate. The efficacy of β-blockers is well established and recent data document the effectiveness of this intervention even in patients with congestive heart failure. It has to be noted that efficacy of β-blockers is associated with and, at least in part, due to heart rate reduction. As an alternative to antiadrenergic intervention, the hypothesis exists that an increase in cardiac vagal activity, as detected by an increase in Heart Rate Variability (HRV) or baroreflex sensitivity (BRS), may be beneficial in the ischemic heart. Supportive of this approach is the evidence that ventricular fibrillation during acute myocardial ischemia may be largely prevented by electrical stimulation of the right cervical vagus or by pharmacological stimulation of cholinergic receptors with oxotremorine. However, there is an inherent danger in the so far unwarranted assumption that modification of HRV or BRS translates directly in cardiac protection. It should be remembered that the target is the improvement in cardiac electrical stability and that BRS or HRV are just markers of autonomic activity. Low dose scopolamine increases HRV in patients with a prior myocardial infarction (MI). This observation has lead to study of the effect of vagal modulation by low dose scopolamine on arrhythmic risk after MI. We tested low dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective and found that this intervention does indeed increase cardiac vagal markers but has minimal antifibrillatory effects. This is at variance from exercise training that, in the same experimental model, had a marked effect on both baroreflex sensitivity and HRV and at the same time provided strong protection from ischemic ventricular fibrillation. Thus, based on the current knowledge it seems appropriate to call for caution before attributing excessive importance to changes in “markers” of vagal activity in the absence of clear-cut evidence for a causal relation with an antifibrillatory effect.