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The role of pacing rate in the modulation of mechano-induced immediate and delayed changes in the force and Ca-transient of cardiac muscle.
Progress in Biophysics and Molecular Biology ( IF 3.2 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.pbiomolbio.2020.05.005
Oleg Lookin 1 , Xenia Butova 1 , Yuri Protsenko 2
Affiliation  

Myocardial function is tuned by dynamic changes in length and load via mechano-calcium feedback. This regulation may be significantly affected by heart rhythm. We evaluated the mechano-induced modulation of contractility and Ca-transient (CaT) in the rat myocardium subjected to twitch-by-twitch shortening–re-lengthening (↓–↑) trains of different lengths (N = 1 … 720 cycles) at low (1 Hz) and near-physiological (3.5 Hz) pacing rates. Force/CaT characteristics were evaluated in the first post-train isometric twitch (immediate effect) and during slow changes (delayed maximal elevation/decrease) and compared with those of the pre-train twitch. The immediate inotropic effect was positive for N = 30 … 720 and negative for N = 1 … 20, while the delayed effect was always positive. The immediate and delayed inotropic effects were significantly higher at 3.5-Hz vs 1-Hz (P < 0.05). The prominent inotropism was accompanied by much smaller changes in the CaT diastolic level/amplitude. The shortening–re-lengthening train induced oscillations of the slow change in force at 3.5-Hz (always) and at 1-Hz (∼50% of muscles), which were dependent of the train length and independent of the pacing rate. We suggest that twitch-by-twitch shortening–re-lengthening of cardiac muscle decreases Ca2+ buffering by troponin C and elevates Ca2+ loading of the sarcoplasmic reticulum (SR); the latter cumulatively depends on the train length. A high pacing rate intensifies the cumulative transient shift in the SR Ca2+ loading, augmenting the post-train inotropic response and prolonging its recovery to the pre-train level. The pacing-dependent mechano-induced inotropic effects remain to be elucidated in the myocardium with impaired Ca handling.



中文翻译:

起搏率在调节机械诱导的心肌力和 Ca 瞬态的即时和延迟变化中的作用。

心肌功能通过机械钙反馈通过长度和负荷的动态变化来调节。这种调节可能会受到心律的显着影响。我们评估了在经过不同长度(N  = 1 … 720 个循环)的逐次缩短-再延长(↓-↑)训练的大鼠心肌中机械诱导的收缩性和 Ca-瞬态(CaT)调节。低 (1 Hz) 和接近生理 (3.5 Hz) 的起搏率。在第一次训练后等长抽搐(即刻效果)和缓慢变化期间(延迟最大升高/减少)评估力/CaT 特性,并与训练前抽搐的特征进行比较。即时性肌力作用是积极的Ñ  = 30 ... 720和阴性Ñ = 1 ... 20,而延迟效应始终为正。3.5-Hz1-Hz的即时和延迟性肌力作用显着更高(P  < 0.05)。显着的正性肌力伴随着更小的 CaT 舒张压水平/幅度变化。缩短 - 再延长列车在 3.5 Hz(始终)和 1 Hz(约 50% 的肌肉)下引起力的缓慢变化的振荡,这取决于列车长度且与起搏速率无关。我们建议心肌的逐次收缩缩短 - 再延长会降低肌钙蛋白 C 对Ca 2+ 的缓冲并提高 Ca 2+加载肌浆网(SR);后者累积取决于列车长度。高起搏率加强了 SR Ca 2+负载的累积瞬态变化,增强了训练后的肌力反应并延长了其恢复到训练前的水平。在 Ca 处理受损的心肌中,起搏依赖性机械诱导的正性肌力作用仍有待阐明。

更新日期:2020-05-23
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