Scopolamine increases vagal tone and vagal reflexes in patients after myocardial infarction.
OBJECTIVE
The goal of this study was to assess the hypothesis that transdermal scopolamine would increase vagal activity in patients after myocardial infarction.


BACKGROUND
In postmyocardial infarction patients, low heart rate variability and reduced baroreceptor reflex sensitivity are associated with increased mortality. Accordingly, there is an increasing interest in a mechanism for shifting the sympathovagal balance toward vagal dominance.


METHODS
The effects of transdermal administration of scopolamine on heart rate variability and baroreceptor reflex sensitivity were assessed in 20 patients (mean age 59 +/- 11 years) by pharmacologic washout 14 +/- 3 days after myocardial infarction. Heart rate variability and baroreceptor reflex sensitivity were measured 24 h after application of the scopolamine patch and compared with the values measured before scopolamine and after application of a placebo patch. The following variables were derived from a 15-min electrocardiographic recording: the mean RR interval and its standard deviation, the mean square successive difference, the percent of intervals differing > 50 ms from the preceding RR interval and the low and high frequency areas resulting from power spectral analysis.


RESULTS
The placebo patch had no effect on the variables measured. Scopolamine increased both heart rate variability and baroreceptor reflex sensitivity significantly. Specifically, the mean RR interval and its standard deviation increased by 7.1% (p = 0.01) and 25% (p = 0.004), respectively. The mean square successive difference increased by 38% (p = 0.0003) and the percent of intervals differing > 50 ms from the preceding interval by 100% (p = 0.001). The ratio of low to high frequency areas of the power spectrum decreased by 24% (p = 0.02), and baroreceptor reflex sensitivity increased by 42% (p = 0.0006). These effects were also evident in patients with very low initial values. Side effects were minimal.


CONCLUSIONS
Transdermal scopolamine increased measures of heart rate variability and baroreceptor reflex sensitivity in patients with a recent myocardial infarction toward values associated with a better prognosis. Pharmacologic modulation of the autonomic balance by scopolamine or related drugs deserves evaluation as a new and promising approach to reduce risk after myocardial infarction.
De Ferrari
G M
GM
Centro di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Italy.
Mantica
M
M
Vanoli
E
E
Hull
S S
SS
Schwartz
P J
PJ
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D017704:Baroreflex / Q000187:drug effects*; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D011379:Prognosis; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012815:Signal Processing, Computer-Assisted; D013318:Stroke Volume; D014630:Vagus Nerve / Q000187:drug effects*
D012601:Scopolamine