Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats.
Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats.
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DOI：
10.1152/ajpheart.00293.2020
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发表时间：
2020-10-02
期刊：
影响因子：
--
通讯作者：
Kay MW
中科院分区：
文献类型：
--
作者：
Zasadny FM;Dyavanapalli J;Dowling NM;Mendelowitz D;Kay MW
左心室电不适应衰竭心肌心率的增加是导致发病率和死亡率的原因之一。最近，心脏胆碱能神经元的激活减少了大鼠慢性横升主动脉缩窄（TAC）引起的收缩功能丧失。我们假设慢性激活心脏胆碱能神经元也会减少tac引起的心脏电活动紊乱。我们研究了TAC大鼠在下丘脑催产素神经元每日化学激活和不每日化学激活的情况下对心脏下游胆碱能神经元的电生理速率适应。在给予或不给予12周的每日化学化治疗后，在动态起搏下切除Sprague-Dawley大鼠心脏，灌注，并进行光学定位。分析60%复极动作电位持续时间（APD60）和传导速度（CV）图对动态起搏的区域速率适应。在较低起搏速率下，未经治疗的TAC诱导左室心外膜APD60升高。治疗后TAC心脏APD60稳态（APDss）降低。在较高起搏速率下，与未治疗的TAC心脏相比，治疗异质性降低了APD60。在快速起搏过程中，与未治疗心脏相比，治疗心脏的传导损失方差降低。然而，在动态起搏过程中，治疗和未治疗的TAC心脏的CV均显著降低。在起搏周期长度为150 ms时，与未治疗心脏相比，治疗心脏的APD60和舒张期离散度降低。心脏胆碱能神经元的慢性激活改善了tac诱导心力衰竭发展过程中对起搏速率增加的电生理适应。这为胆碱能刺激作为治疗心力衰竭患者的电生理益处提供了见解。新的和值得注意的电生理学分析，从失败的左心室心肌光学测绘提供了对左心室胆碱能刺激可能的治疗结果的见解。慢性下丘脑催产素神经元激活对心脏下游胆碱能神经元的刺激可减弱压力过载心力衰竭大鼠电生理功能衰竭的发生。
Left ventricular (LV) electrical maladaptation to increased heart rate in failing myocardium contributes to morbidity and mortality. Recently, cardiac cholinergic neuron activation reduced loss of contractile function resulting from chronic transverse-ascending aortic constriction (TAC) in rats. We hypothesized that chronic activation of cardiac cholinergic neurons would also reduce TAC-induced derangement of cardiac electrical activity. We investigated electrophysiological rate adaptation in TAC rat hearts with and without daily chemogenetic activation of hypothalamic oxytocin neurons for downstream cardiac cholinergic neuron stimulation. Sprague–Dawley rat hearts were excised, perfused, and optically mapped under dynamic pacing after 16 wk of TAC with or without 12 wk of daily chemogenetic treatment. Action potential duration at 60% repolarization (APD60) and conduction velocity (CV) maps were analyzed for regional rate adaptation to dynamic pacing. At lower pacing rates, untreated TAC induced elevated LV epicardial APD60. Fitted APD60 steady state (APDss) was reduced in treated TAC hearts. At higher pacing rates, treatment heterogeneously reduced APD60, compared with untreated TAC hearts. Variance of conduction loss was reduced in treated hearts compared with untreated hearts during fast pacing. However, CV was markedly reduced in both treated and untreated TAC hearts throughout dynamic pacing. At 150 ms pacing cycle length, APD60 versus diastolic interval dispersion was reduced in treated hearts compared with untreated hearts. Chronic activation of cardiac cholinergic neurons improved electrophysiological adaptation to increases in pacing rate during the development of TAC-induced heart failure. This provides insight into the electrophysiological benefits of cholinergic stimulation as a treatment for patients with heart failure. NEW & NOTEWORTHY Analysis of electrophysiology from optical mapping of failing left ventricular myocardium provided insight into the possible therapeutic outcomes of cholinergic stimulation within the left ventricle. Chronic hypothalamic oxytocin neuron activation for downstream cardiac cholinergic neuron stimulation blunted onset of failing electrophysiology induced by pressure overload-induced heart failure in rats.
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