BACKGROUND: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI. METHODS AND RESULTS: Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93). CONCLUSIONS: In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.
RCT Entities:
BACKGROUND: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI. METHODS AND RESULTS:Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93). CONCLUSIONS: In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.