EFFECTS OF ORAL PIRENZEPINE ON HEART-RATE-VARIABILITY AND BARORECEPTOR REFLEX SENSITIVITY AFTER ACUTE MYOCARDIAL-INFARCTION

Objectives. Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. Background. Depression of vagal tone and reflexes predic ts a poor arrhythmic outcome after myocardial infarction, Intervention s for shifting the sympathovagal balance toward vagal dominance are no w of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. Methods. In a single-blind placebo-c ontrolled crossover trial, short-term RR interval variability and baro receptor reflex sensitivity were evaluated in 20 patients an average o f 19 +/- 6 days after infarction. Analysis was performed during contro l conditions and during administration of placebo, oral pirenzepine an d transdermal scopolamine. Results. Compared with placebo, at a dose o f 25 mg mice daily, pirenzepine significantly increased all time and f requency domain measures of RR interval variability and augmented baro receptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine shelved a similar vagomimetic effect, but the overall incidence of adverse effec ts was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). Concl usions. In patients with a recent myocardial infarction, oral pirenzep ine proved equal to transdermal scopolamine in significantly increasin g indexes of cardiac vagal activity. These data suggest that oral pire nzepine may have a therapeutic potential for preventing malignant vent ricular arrhythmias after infarction.