Reil Jan-Christian, Tauchnitz Marcus, Tian Qinghai, Hohl Mathias, Linz Dominik, Oberhofer Martin, Kaestner Lars, Reil Gert-Hinrich, Thiele Holger, Steendijk Paul, Böhm Michael, Neuberger Hans-Ruprecht, Lipp Peter
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; Klinik für Innere Medizin II, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitäres Herzzentrum Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany;
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Am J Physiol Heart Circ Physiol. 2016 Oct 1;311(4):H1014-H1023. doi: 10.1152/ajpheart.00261.2016. Epub 2016 Sep 9.
Patients with hypertension and hyperaldosteronism show an increased risk of stroke compared with patients with essential hypertension. Aim of the study was to assess the effects of aldosterone on left atrial function in rats as a potential contributor to thromboembolism. Osmotic mini-pumps delivering 1.5 μg aldosterone/h were implanted in rats subcutaneously (Aldo, n = 39; controls, n = 38). After 8 wk, left ventricular pressure-volume analysis of isolated working hearts was performed, and left atrial systolic and diastolic function was also assessed by atrial pressure-diameter loops. Moreover, left atrial myocytes were isolated to investigate their global and local Ca handling and contractility. At similar heart rates, pressure-volume analysis of isolated hearts and in vivo hemodynamic measurements revealed neither systolic nor diastolic left ventricular dysfunction in Aldo. In particular, atrial filling pressures and atrial size were not increased in Aldo. Aldo rats showed a significant reduction of atrial late diastolic A wave, atrial active work index, and increased V waves. Consistently, in Aldo rats, sarcomere shortening and the amplitude of electrically evoked global Ca transients were substantially reduced. Sarcoplasmic reticulum-Ca content and fractional Ca release were decreased, substantiated by a reduced sarcoplasmic reticulum calcium ATPase activity, resulting from a reduced CAMKII-evoked phosphorylation of phospholamban. Hyperaldosteronism induced atrial systolic and diastolic dysfunction, while atrial size and left ventricular hemodynamics, including filling pressures, were unaffected in rats. The described model suggests a direct causal link between hyperaldosteronism and decreased atrial contractility and diastolic compliance.
与原发性高血压患者相比，高血压和醛固酮增多症患者发生中风的风险更高。本研究的目的是评估醛固酮对大鼠左心房功能的影响，因为这可能是导致血栓栓塞的一个因素。将每小时输送1.5μg醛固酮的渗透微型泵皮下植入大鼠体内（醛固酮组，n = 39；对照组，n = 38）。8周后，对离体工作心脏进行左心室压力-容积分析，并通过心房压力-直径环评估左心房的收缩和舒张功能。此外，分离左心房肌细胞以研究其整体和局部钙处理及收缩性。在相似心率下，离体心脏的压力-容积分析和体内血流动力学测量结果显示，醛固酮组大鼠的左心室收缩和舒张功能均未受损。特别是，醛固酮组大鼠的心房充盈压和心房大小并未增加。醛固酮组大鼠的心房舒张晚期A波、心房主动作功指数显著降低，V波增加。同样，醛固酮组大鼠的肌节缩短和电诱发的整体钙瞬变幅度也大幅降低。肌浆网钙含量和钙释放分数降低，这是由于受磷蛋白的钙调蛋白依赖性蛋白激酶II（CAMKII）诱发的磷酸化减少，导致肌浆网钙ATP酶活性降低所致。醛固酮增多症可导致心房收缩和舒张功能障碍，而大鼠的心房大小和左心室血流动力学（包括充盈压）未受影响。所述模型表明醛固酮增多症与心房收缩性降低和舒张顺应性降低之间存在直接因果关系。
