Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium.
Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium.
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分离的衰竭和非衰竭人类心肌中的 Ca2 处理和肌浆网 Ca2 含量。
DOI：
10.1161/01.res.85.1.38
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发表时间：
1999
影响因子：
20.1
通讯作者：
Hasenfuss,G
中科院分区：
文献类型：
--
作者：
Pieske,B;Maier,LS;Bers,DM;Hasenfuss,G
肌浆网（SR）Ca 2+含量的紊乱可能是衰竭心肌力-频率和静息后收缩行为改变的基础。我们使用快速冷却挛缩（RCCs）来评估从非衰竭和终末期衰竭人类心脏分离的心室肌条中SR Ca 2+含量。随着静息间期的增加（1 ~ 240 s; 37°C），非衰竭的人心肌（n=7）表现出静息后收缩力（240 s时为121±44%;P<0.05）和RCC振幅（69±53%;P<0.05）的平行增加。相反，在衰竭心肌（n=30）中，长休息间隔时静息后收缩力下降，RCC振幅随休息单调下降（分别为25±9%和53± 9%;P<0.05）。随着刺激频率的增加（0.25 ~ 3 Hz），正常人心肌（n=7）的收缩力持续增加71±17%（3 Hz;P<0.05），RCC振幅增加247±55%（P<0.05）。而衰竭心肌（n=26），收缩力下降29±7%（P<0.05），RCC振幅仅增加36±14%（P<0.05）。诱发成对的RCCs，以研究松弛过程中SR Ca 2+摄取和Na+/Ca 2+交换对胞浆Ca 2+清除的相对贡献。SR Ca 2+摄取（相对于Na+/Ca 2+交换）增加显着在nonfailing，但不是在失败的人心肌刺激率增加。我们得出结论，在失败的人心肌的负力-频率关系是由于SR Ca 2+含量无法增加足够的高频率，从而不能克服频率依赖性的不应性SR Ca 2+释放。衰竭心肌中收缩力的静息依赖性衰减是由于SR Ca 2+含量的静息依赖性下降。这些变化可能是继发于抑制SR Ca 2 +-ATP酶结合增强胞质Ca 2+挤出通过Na+/Ca 2+交换。
—Disturbed sarcoplasmic reticulum (SR) Ca2+content may underlie the altered force-frequency and postrest contractile behavior in failing human myocardium. We used rapid cooling contractures (RCCs) to assess SR Ca2+content in ventricular muscle strips isolated from nonfailing and end-stage failing human hearts. With an increase in rest intervals (1 to 240 s; 37°C), nonfailing human myocardium (n=7) exhibited a parallel increase in postrest twitch force (at 240 s by 121±44%;P<0.05) and RCC amplitude (by 69±53%;P<0.05). In contrast, in failing myocardium (n=30), postrest twitch force decreased at long rest intervals and RCC amplitude declined monotonically with rest (by 25±9% and 53±9%, respectively;P<0.05). With an increase in stimulation frequencies (0.25 to 3 Hz), twitch force increased continuously in nonfailing human myocardium (n=7) by 71±17% (at 3 Hz;P<0.05) and RCC amplitude increased in parallel by 247±55% (P<0.05). In contrast, in failing myocardium (n=26), twitch force declined by 29±7% (P<0.05) and RCC amplitude increased only slightly by 36±14% (P<0.05). Paired RCCs were evoked to investigate the relative contribution of SR Ca2+uptake and Na+/Ca2+exchange to cytosolic Ca2+removal during relaxation. SR Ca2+uptake (relative to the Na+/Ca2+exchange) increased significantly in nonfailing but not in failing human myocardium as stimulation rates increased. We conclude that the negative force-frequency relation in failing human myocardium is due to an inability of SR Ca2+content to increase sufficiently at high frequencies and thus cannot overcome the frequency-dependent refractoriness of SR Ca2+release. The rest-dependent decay in twitch force in failing myocardium is due to rest-dependent decline in SR Ca2+content. These alterations could be secondary to depressed SR Ca2+-ATPase combined with enhanced cytosolic Ca2+extrusion via Na+/Ca2+exchange.