Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City; Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Anesthesiology, Taipei Veterans General Hospital; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Chin J Physiol. 2022 Sep-Oct;65(5):241-249. doi: 10.4103/0304-4920.358234.
Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.
体外循环（CPB）会消耗内源性维生素 C 并在心脏手术中产生氧化应激。本研究旨在阐明维生素 C 补充是否可以减少心脏手术 CPB 中的氧化剂产生并改善红细胞变形性。在一项随机对照设计中，30 名符合条件的接受低温 CPB 心脏手术的患者被平均分配到维生素 C 组和对照组。CPB 复温期间，维生素 C 组和对照组患者分别接受静脉输注维生素 C 20mg·kg 和安慰剂。我们测量了 CPB 前后红细胞膜中活性氧（ROS）的血浆水平和非肌球蛋白 IIA（NMIIA）的磷酸化水平，作为红细胞变形性的指标。CPB 后，维生素 C 补充可减轻血浆 ROS 的激增，维生素 C 组的平均值为 1.661±标准偏差 0.801 倍，对照组为 2.743±1.802。与对照组相比，CPB 后维生素 C 组 NMIIA 的酪氨酸磷酸化水平升高，为 2.159±0.887 倍和 1.384±0.445（P=0.0237）。此外，CPB 后，红细胞中的血管扩张刺激磷蛋白（VASP）和粘着斑激酶（FAK）的磷酸化也同时增强。CPB 后，维生素 C 组红细胞内皮型一氧化氮合酶的磷酸化水平显著升高（1.734±0.371 倍），而对照组为 1.102±0.249（P=0.0061）。与对照组相比，接受维生素 C 的患者在 CPB 后术中出血量减少，全身血管阻力增加。CPB 期间，通过 VASP/FAK 信号通路，维生素 C 补充可减轻氧化应激并改善红细胞变形性。
