Schotten Ulrich, Greiser Maura, Benke Dirk, Buerkel Kai, Ehrenteidt Britta, Stellbrink Christoph, Vazquez-Jimenez Jaime F, Schoendube Friedrich, Hanrath Peter, Allessie Maurits
Department of Physiology, University Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Cardiovasc Res. 2002 Jan;53(1):192-201. doi: 10.1016/s0008-6363(01)00453-9.
Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood.
From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer.
In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AF patients.
AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.
虽然房颤引起的心房收缩功能障碍具有重要的临床意义，但其潜在的细胞内机制仍知之甚少。
从59例连续接受二尖瓣手术的患者的右心耳（31例处于窦性心律，28例处于慢性房颤）中分离出细肌条（直径<0.7mm）。在存在不同浓度的Ca(2+)和异丙肾上腺素的情况下测量等长收缩力。为评估肌浆网的功能，研究了力-频率关系和静息后增强效应。通过[3H]ryanodine结合测定肌浆网中对ryanodine敏感的钙释放通道（CRC）的心肌密度。通过蛋白质印迹分析来分析肌浆网Ca(2+)-ATP酶（SERCA）、受磷蛋白（Plb）、肌钙蛋白（Cals）和钠/钙交换体（NCX）的心肌含量。使用[32P]ATP作为示踪剂通过放射性标记生物测定法测量腺苷酸环化酶活性。
在窦性心律患者的72条肌条中，收缩力为10.9±1.8mN/mm(2)，而房颤患者为3.3±0.9mN/mm(2)（n=48，P<0.01）。异丙肾上腺素的正性肌力作用减弱，但对房颤患者的舒张刺激作用和腺苷酸环化酶未改变。房颤患者心房心肌中的力-频率关系和静息后增强效应增强。两组之间CRC、SERCA、Plb和Cals的蛋白质水平没有差异。相反，房颤患者心房中的钠/钙交换体上调了67%。
房颤引起的心房收缩功能障碍不是由于β-肾上腺素能脱敏或肌浆网功能障碍，因此其细胞机制与室性心动过速引起的心肌病不同。相反，L型Ca(2+)通道的下调或功能改变以及通过钠/钙交换体增加的Ca(2+)外流似乎是重构心房收缩力降低的原因。
