Subacute pyridostigmine exposure increases heart rate recovery and cardiac parasympathetic tone in rats.

Subacute pyridostigmine exposure increases heart rate recovery and cardiac parasympathetic tone in rats.
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DOI:
10.1111/1440-1681.12773
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发表时间:
2017-08
影响因子:
2.9
通讯作者:
Maxwell L
Maxwell L
中科院分区:
医学4区
文献类型:
--
作者:
Bharadwaj M;Pope C;Davis M;Katz S;Cook C;Maxwell L

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心率恢复(HRR)描述剧烈运动后心率的快速减速,是副交感神经张力的指标。充血性心力衰竭患者副交感神经张力降低,导致心率变异性延长。乙酰胆碱酯酶抑制剂,如吡斯的明,可以通过增加对心脏的胆碱能输入来增强副交感神经张力。本研究的目的是建立一种大鼠HRR模型,以验证亚急性给药降低胆碱酯酶活性和加速HRR的假说。植入放射性遥测发射机后10天,雄性SD大鼠随机分为对照组(CTL)和治疗组(饮水中吡斯的明0.14 mg/ml,29天)。大鼠在跑步机上运动,记录心率,分别于给药第0、7、14、28天采集血样。PYR大鼠血浆总胆碱酯酶和乙酰胆碱酯酶(AChE)活性在第7~28天分别下降32~43%和57~80%,而血浆丁酰胆碱酯酶活性无明显变化。红细胞乙酰胆碱酯酶活力明显降低,-66%。PYR组运动后1min的HRR在第7、14、28d较高,第7天HRR估计为3、5min。对自主神经张力进行药理学评估,采用毒鼠强(阿托品)和肾上腺素能(心得安)阻滞剂的顺序给药。与CTL组相比,PYR组大鼠副交感神经张力增加。这些数据支持亚急性吡斯的明给药通过增加心脏副交感神经张力来增强心率变异性的研究假设。
Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can enhance parasympathetic tone by increasing cholinergic input to the heart. The objective of this study was to develop a rodent model of HRR to test the hypothesis that subacute pyridostigmine administration decreases cholinesterase activity and accelerates HRR in rats. Ten days after implantation of radiotelemetry transmitters, male Sprague Dawley rats were randomized to control (CTL) or treated (PYR; 0.14 mg/ml pyridostigmine in the drinking water, 29 days) groups. Rats were exercised on a treadmill to record HRR, and blood samples were collected on days 0, 7, 14, and 28 of pyridostigmine administration. Total cholinesterase and acetylcholinesterase (AChE) activity in plasma was decreased by 32–43% and 57–80%, respectively, in PYR rats on days 7–28, while plasma butyrylcholinesterase activity did not significantly change. AChE activity in RBCs was markedly reduced by 64–66%. HRR recorded 1 min after exercise was higher in the PYR group on days 7, 14 and 28, and on day 7 when HRR was estimated at 3 and 5 min. Autonomic tone was evaluated pharmacologically using sequential administration of muscarinic (atropine) and adrenergic (propranolol) blockers. Parasympathetic tone was increased in PYR rats as compared with the CTL group. These data support the study hypothesis that subacute pyridostigmine administration enhances HRR by increasing cardiac parasympathetic tone.
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发表时间: 2007-07-01
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DOI: 10.1136/heart.89.8.854
发表时间: 2003-08-01
期刊: HEART
影响因子: 5.7
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