Kaya Dayimi, Ellidokuz Ender, Onrat Ersel, Ellidokuz Hulya, Celik Atac, Kilit Celal
Department of Cardiology, School of Medicine Afyon Kocatepe University, Afyon, Turkey.
Clin Auton Res. 2003 Aug;13(4):275-80. doi: 10.1007/s10286-003-0097-3.
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.
多巴胺2（D2）样受体拮抗剂被广泛用于治疗胃轻瘫和呕吐。甲氧氯普胺（MCP）是一种外周和中枢D2样受体拮抗剂，可刺激交感神经系统并可能改变自主神经调节，但MCP对心脏的总体影响尚不清楚。我们研究的目的是使用心率变异性功率谱分析来研究MCP对心脏自主神经调节的影响。我们评估了9名健康男性在长时间仰卧和站立姿势期间MCP对心脏自主神经调节的影响。在连续心电图记录期间，我们以双盲和交叉方式对所有参与者静脉注射10 mg MCP和安慰剂。在仰卧位15分钟后（休息阶段）给予安慰剂或MCP，参与者在该位置再停留50分钟（仰卧后阶段），然后站立10分钟（站立阶段）。选择5分钟间隔进行功率谱分析，并计算功率谱低频（LF）、LF标准化单位（LFnu）、高频（HF）、HF标准化单位（HFnu）分量以及LF/HF比值的平均值。安慰剂给药期间心率变化具有统计学意义（Friedman检验p<0.0001）。事后分析表明，这些变化与仰卧后阶段心率降低和站立阶段心率增加有关。仰卧后阶段LFnu有降低趋势（Friedman检验p = 0.050），但安慰剂给药期间LF/HF比值变化未达到统计学显著水平。MCP给药可防止心率下降，且在仰卧后阶段可观察到安慰剂组出现的LFnu分量降低。MCP给药期间心率变化也达到显著水平（Friedman检验p = 0.002），事后分析表明这些变化主要与站立阶段心率增加有关。与安慰剂不同，MCP给药导致LFnu和LF/HF比值出现显著变化（分别为Friedman检验p = 0.004和p = 0.003）。LF/HF比值变化的双向方差分析模型表明，在研究的每个阶段，MCP诱导的LF/HF比值上升幅度均显著高于安慰剂（F = 5.570；p = 0.031）。我们得出结论，MCP对交感迷走神经平衡的总体影响是增加了对心脏的交感神经驱动。MCP可防止长时间仰卧位期间对心脏交感神经驱动的降低，并在轻度交感神经刺激（如站立引起的刺激）期间增强对心脏的交感神经驱动。
