Division of Cardiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Department of Mechanical Engineering, University of Texas at San Antonio, San Antonio, Texas.
J Appl Physiol (1985). 2019 Aug 1;127(2):457-463. doi: 10.1152/japplphysiol.00087.2019. Epub 2019 Jun 20.
Heart failure with preserved ejection fraction (HFpEF) is a common cause of hospital admission in patients over 65 yr old and has high mortality. HFpEF is characterized by left ventricular (LV) hypertrophy that reduces compliance. Current HFpEF therapies control symptoms, but no existing medications or therapies can sustainably increase LV compliance. LV trabeculae develop hypertrophy and fibrosis that contribute to reduced LV compliance. This study expands our previous results in ex vivo human hearts to show that severing LV trabeculae increases diastolic compliance in an ex vivo working rabbit heart model. Trabecular cutting was performed in ex vivo rabbit hearts set up in a working heart perfusion system perfused with oxygenated Krebs-Henseleit buffer. A hook was inserted in the LV to cut trabeculae. End-systolic and end-diastolic pressure-volume relationships during transient preload reduction were recorded using an admittance catheter in the following three groups: control (no cutting; = 9), mild cutting (15 cuts; = 5), and aggressive cutting (30 cuts; = 5). In a second experiment, each heart served as its own control. Hemodynamic data were recorded before and after trabecular cutting ( = 10) or sham cutting ( = 5) within the same heart. In the first experiments, trabecular cutting did not affect systolic function ( > 0.05) but significantly increased overall diastolic compliance ( = 0.009). Greater compliance was seen as trabecular cutting increased ( = 0.002, = 0.435). In the second experiment, significant increases in systolic function ( = 0.048) and diastolic compliance ( = 0.002) were seen after trabecular cutting compared with baseline. In conclusion, trabecular cutting significantly increases diastolic compliance without reducing systolic function. We postulate that, in mammalian hearts, free-running trabeculae carneae exist to provide tensile support to the left ventricle and minimize diastolic wall stress. Because of hypertrophy and fibrosis of trabeculae in patients with left ventricular hypertrophy, this supportive role can become pathologic, worsening diastolic compliance. We demonstrate a novel operation involving cutting trabeculae as a method to acutely increase diastolic compliance in patients presenting with heart failure and diastolic dysfunction to improve their left ventricle compliance.
射血分数保留的心力衰竭(HFpEF)是 65 岁以上患者住院的常见原因,死亡率很高。HFpEF 的特征是左心室(LV)肥厚,降低顺应性。目前的 HFpEF 治疗方法可以控制症状,但没有现有的药物或治疗方法可以持续增加 LV 顺应性。LV 小梁发生肥大和纤维化,导致 LV 顺应性降低。本研究将我们之前在离体人心上的结果扩展到显示,在离体工作兔心模型中,切断 LV 小梁可增加舒张顺应性。在使用含氧 Krebs-Henseleit 缓冲液灌注的工作心脏灌注系统中,将钩插入 LV 以切断小梁。在以下三组中记录短暂前负荷降低期间的收缩末期和舒张末期压力-容积关系:对照(无切割;n = 9)、轻度切割(15 刀;n = 5)和激进切割(30 刀;n = 5)。在第二个实验中,每个心脏都作为自己的对照。在小梁切割(n = 10)或假切割(n = 5)前后记录同一心脏内的血流动力学数据。在第一个实验中,小梁切割不影响收缩功能(>0.05),但显著增加整体舒张顺应性(=0.009)。随着小梁切割的增加,顺应性更大(=0.002,=0.435)。在第二个实验中,与基线相比,小梁切割后收缩功能(=0.048)和舒张顺应性(=0.002)显著增加。总之,小梁切割可显著增加舒张顺应性而不降低收缩功能。我们推测,在哺乳动物心脏中,游离的肉柱小梁存在是为了提供左心室的拉伸支撑,最大限度地降低舒张期壁应力。由于肥厚性心肌病患者的小梁肥大和纤维化,这种支撑作用可能会变得病态,从而使舒张顺应性恶化。我们展示了一种涉及切割小梁的新手术,作为一种在心力衰竭和舒张功能障碍患者中急性增加舒张顺应性的方法,以改善他们的左心室顺应性。