AUTONOMIC CONTROL OF HEART-RATE - PHARMACOLOGICAL AND NONPHARMACOLOGICAL MODULATION

The evidence of the predictive value of autonomic markers has generate d a growing interest for interventions able to influence autonomic con trol of heart rate. The hypothesis is that an increase in cardiac vaga l activity as detected by an increase in heart rate variability (HRV) or baroreflex sensitivity (BRS) may be beneficial in the ischemic hear t. Numerous experimental data support the hypothesis that augmenting v agal 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 stimulatio n of the right cervical vagus or by pharmacological stimulation of cho linergic receptors with oxotremorine. There is an inherent danger in t he so far unwarranted assumption that modification of HRV or BRS trans lates directly in cardiac protection. This may or may not be the case. It should be remembered that the true target is the improvement in ca rdiac electrical stability and that BRS or HRV are just markers of aut onomic activity. Low dose scopolamine increases HRV in patients with a prior myocardial infarction. This observation, combined with the evid ence that elevated cardiac vagal activity during acute myocardial isch emia is antifibrillatory, has generated the hypothesis that scopolamin e might be protective after MI. We tested low dose scopolamine in a cl inically relevant experimental preparation for sudden death in which o ther vagomimetic interventions are effective and found that this inter vention does indeed increase cardiac vagal markers but has minimal ant ifibrillatory effects. This is in contrast to exercise training that i n the same experimental model had a marked effect on both BRS and HRV and at the same time provided strong protection from ischemic ventricu lar fibrillation. Thus, based on the current knowledge it seems approp riate to call for caution before attributing excessive importance to c hanges in ''markers'' of vagal activity in the absence of clearcut evi dence for a causal relation with an antifibrillatory effect.