Dopamine2 (D2)-like
receptor antagonists are widely
used for the treatment of gastroparesis
and vomiting. Metoclopramide
(MCP), a peripheral and
central D2-like receptor antagonist,
stimulates the sympathetic nervous
system and may alter autonomic
modulation, but the net effect of
MCP to the heart is not known. The
aim of our study was to investigate
the effects of MCP on cardiac autonomic
modulation, using power
spectral analysis of heart rate variability.
We evaluated the effect of MCP
on cardiac autonomic modulation
during prolonged supine and
standing positions in 9 healthy
men. We intravenously administered
10 mg MCP and placebo
in a double blind and crossover
manner to all participants during
continuous electrocardiography
recording. Placebo or MCP was administered
after 15 minutes in
supine position (REST phase),
where participants remained for an
additional 50 minutes (PSUP
phase) and then stood up for 10
minutes (STA phase). Five-minute
intervals were selected for power
spectral analysis, and average values
were calculated for low frequency
(LF), normalized unit of LF
(LFnu), high frequency (HF), normalized
unit of HF (HFnu) components
of the power spectrum, and
for LF/HF ratio.
Heart rate alterations were statistically
significant during placebo
administration (Friedman
s
p < 0.0001). These changes were related
to the decrease in PSUP phase
and increase in STA phase in post
hoc analyses. There was a trend toward
lower LFnu in PSUP phase
(Friedman
s p = 0.050), but LF/HF
ratio changes did not reach a statistically
significant level during
placebo administration. MCP administration
prevented the decrease
in heart rate and LFnu component
was seen with placebo in
PSUP phase. Heart rate alterations
also reached a significant level during
MCP administration (Friedman
s
p = 0.002), and post hoc
analyses showed that these changes
were mainly related to the increase
in STA phase. In contrast to
placebo, MCP administration resulted
in significant alterations in
LFnu and LF/HF ratio (Friedman
s
p = 0.004 and p = 0.003, respectively).
Two-way ANOVA model for
LF/HF ratio changes showed that
MCP induced a significant upward
shift in LF/HF ratio than placebo
during each phase of the study
(F = 5.570; p = 0.031).
We concluded that the net effect
of MCP on sympathovagal balance
is an increased sympathetic drive
to the heart. MCP prevented the
decrease in sympathetic drive to
the heart during prolonged supine
position and augmented sympathetic
drive to the heart during
mild sympathetic stimulation such
as induced by standing up.
Key words D2-like receptor - Metoclopramide - HRV - sympathovagal balance