Department of Physiology, University of Auckland, Auckland, New Zealand.
Greenlane Cardiothoracic Surgical Unit, Auckland City Hospital, Auckland, New Zealand.
Physiol Rep. 2023 Feb;11(3):e15599. doi: 10.14814/phy2.15599.
The aim of this study was to investigate cardiomyocyte Ca handling and contractile function in freshly excised human atrial tissue from diabetic and non-diabetic patients undergoing routine surgery. Multicellular trabeculae (283 ± 20 μm in diameter) were dissected from the endocardial surface of freshly obtained right atrial appendage samples from consenting surgical patients. Trabeculae were mounted in a force transducer at optimal length, electrically stimulated to contract, and loaded with fura-2/AM for intracellular Ca measurements. The response to stimulation frequencies encompassing the physiological range was recorded at 37°C. Myofilament Ca sensitivity was assessed from phase plots and high potassium contractures of force against [Ca ] . Trabeculae from diabetic patients (n = 12) had increased diastolic (resting) [Ca ] (p = 0.03) and reduced Ca transient amplitude (p = 0.04) when compared to non-diabetic patients (n = 11), with no difference in the Ca transient time course. Diastolic stress was increased (p = 0.008) in trabeculae from diabetic patients, and peak developed stress decreased (p ≤ 0.001), which were not accounted for by reduction in the cardiomyocyte, or contractile protein, content of trabeculae. Trabeculae from diabetic patients also displayed diminished myofilament Ca sensitivity (p = 0.018) compared to non-diabetic patients. Our data provides evidence of impaired calcium handling during excitation-contraction coupling with resulting contractile dysfunction in atrial tissue from patients with type 2 diabetes in comparison to the non-diabetic. This highlights the importance of targeting cardiomyocyte Ca homeostasis in developing more effective treatment options for diabetic heart disease in the future.
本研究旨在探究 2 型糖尿病患者与非糖尿病患者经手术获取的新鲜人心房组织中心肌细胞钙处理和收缩功能。从手术患者右心耳心内膜面分离出多细胞小梁（直径 283±20μm），将小梁置于力传感器上，在最佳长度下进行电刺激收缩，并加载 fura-2/AM 以进行细胞内 Ca 测量。在 37°C 下记录涵盖生理范围的刺激频率的反应。通过相位图和力对 [Ca ] 的高钾收缩评估肌球蛋白 Ca 敏感性。与非糖尿病患者（n=11）相比，糖尿病患者（n=12）的小梁舒张（静息）[Ca ]增加（p=0.03），钙瞬变幅度降低（p=0.04），但钙瞬变时程无差异。糖尿病患者的小梁舒张张力增加（p=0.008），最大发展张力降低（p≤0.001），这与小梁中肌细胞或收缩蛋白含量的减少无关。与非糖尿病患者相比，糖尿病患者的小梁肌球蛋白 Ca 敏感性也降低（p=0.018）。与非糖尿病患者相比，本研究数据为 2 型糖尿病患者心房组织在兴奋-收缩偶联过程中钙处理受损，导致收缩功能障碍提供了证据。这突显了在未来针对糖尿病性心脏病开发更有效的治疗方案时，靶向心肌细胞钙稳态的重要性。
