Autonomic control of heart rate: pharmacological and nonpharmacological modulation

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 hypothesis is 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. Numerous experimental data support the hypothesis that augmenting vagal activity might be protective against lethal ischemic arrhythmias. Among them 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. There is an inherent danger in the so far unwarranted assumption that modification of HRV or BRS translates directly in cardiac protection. This may or may not be the case. It should be remembered that the true 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. This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective 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 in contrast to exercise training that in the same experimental model had a marked effect on both BRS 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 clearcut evidence for a causal relation with an antifibrillatory effect.