University Hospital Düsseldorf, Heinrich-Heine-University, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, 40225, Düsseldorf, Germany.
University Hospital Düsseldorf, Heinrich-Heine-University, Medical Faculty, Division of Endocrinology and Diabetology, 40225, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, 40225, Düsseldorf, Germany; German Center for Diabetes Research, 85764, München-Neuherberg, Germany.
Nitric Oxide. 2020 Apr 1;97:1-10. doi: 10.1016/j.niox.2020.01.008. Epub 2020 Jan 22.
Red blood cells (RBCs) play an important role in the cardiac ischemia/reperfusion (I/R) injury. Cardiovascular risk factors impair the RBC function in an endothelial nitric oxide synthase (eNOS) dependent manner. However, it is unclear whether the protective role of RBCs can be rescued by modifying cardiovascular risk factors or by pharmacologic intervention. RBCs obtained from elderly patients with or without diabetes as well as from young volunteers were treated with vehicle, eNOS inhibitor l-NAME and/or arginase inhibitor nor-NOHA before loading to the coronary system of isolated murine hearts in a Langendorff system before 40 min of global ischemia. RBCs from young and healthy volunteers as well as from aged persons and elderly diabetes patients with satisfying blood glucose control improved left ventricular function upon 60 min of reperfusion with Krebs-Henseleit buffer and reduced the infarct size compared to buffer treated controls. This cardioprotective effect was abolished in RBCs from aged diabetes patients with poor blood glucose control. Treatment of RBCs from elderly diabetes patients with nor-NOHA partly rescued the cardioprotective function. Thus, effective glucose control in aged diabetes patients rescues RBC-dependent cardioprotection in an ex-vivo model of myocardial I/R injury.
红细胞（RBCs）在心脏缺血/再灌注（I/R）损伤中起着重要作用。心血管危险因素以内皮型一氧化氮合酶（eNOS）依赖的方式损害 RBC 功能。然而，尚不清楚通过改变心血管危险因素或通过药物干预是否可以挽救 RBC 的保护作用。将来自有或没有糖尿病的老年患者和年轻志愿者的 RBC 用载体、eNOS 抑制剂 l-NAME 和/或精氨酸酶抑制剂 nor-NOHA 处理，然后在 Langendorff 系统中在 40 分钟的整体缺血前加载到分离的小鼠心脏的冠状动脉系统中。来自年轻和健康志愿者以及年龄较大的人和患有糖尿病且血糖控制良好的老年患者的 RBC 在再灌注 60 分钟时用 Krebs-Henseleit 缓冲液改善左心室功能，并与缓冲液处理的对照相比减少梗死面积。在血糖控制不佳的老年糖尿病患者的 RBC 中，这种心脏保护作用被消除。用 nor-NOHA 处理老年糖尿病患者的 RBC 部分挽救了心脏保护功能。因此，在心肌 I/R 损伤的体外模型中，老年糖尿病患者的有效血糖控制可挽救 RBC 依赖性心脏保护作用。
