Ying-Hsuan Tai1,2,3,4, You-Hsiang Chu1,5, Hsiang-Ling Wu1,2, Su-Man Lin1,2, Mei-Yung Tsou1,2, Cheng-Hsiung Huang2,6, Hsiao-Huang Chang6, Chih-Cherng Lu1,5,7. 1. Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan. 2. School of Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. 4. Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 5. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. 6. Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Institute of Aerospace Medicine, National Defense Medical Center, Taipei, Taiwan.
Abstract
OBJECTIVE: We aimed to determine whether high-dose nitroglycerin, a nitric oxide donor, preserves erythrocyte deformability during cardiopulmonary bypass and examines the signaling pathway of nitric oxide in erythrocytes. METHODS: In a randomized and controlled fashion, forty-two patients undergoing cardiac surgery withhypothermic cardiopulmonary bypass were allocated to high-dose (N = 21) and low-dose groups (N = 21). During rewarming period, patients were given intravenous nitroglycerin with an infusion rate 5 and 1 µg·kg-1 ·min-1 in high-dose and low-dose groups, respectively. Tyrosine phosphorylation level of non-muscle myosin IIA in erythrocyte membrane was used as an index of erythrocyte deformability and analyzed using immunoblotting. RESULTS:Tyrosine phosphorylation of non-muscle myosin IIA was significantly enhanced after bypass in high-dose group (3.729 ± 1.700 folds, P = .011) but not low-dose group (1.545 ± 0.595 folds, P = .076). Phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocyte membrane was also upregulated in high-dose group after bypass. Besides, plasma nitric oxide level was highly correlated with fold change of non-muscle myosin IIA phosphorylation (Pearson's correlation coefficient .871). CONCLUSIONS: High-dose nitroglycerin administered during cardiopulmonary bypass improves erythrocyte deformability through activating phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocytes.
RCT Entities:
OBJECTIVE: We aimed to determine whether high-dose nitroglycerin, a nitric oxidedonor, preserves erythrocyte deformability during cardiopulmonary bypass and examines the signaling pathway of nitric oxide in erythrocytes. METHODS: In a randomized and controlled fashion, forty-two patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass were allocated to high-dose (N = 21) and low-dose groups (N = 21). During rewarming period, patients were given intravenous nitroglycerin with an infusion rate 5 and 1 µg·kg-1 ·min-1 in high-dose and low-dose groups, respectively. Tyrosine phosphorylation level of non-muscle myosin IIA in erythrocyte membrane was used as an index of erythrocyte deformability and analyzed using immunoblotting. RESULTS: Tyrosine phosphorylation of non-muscle myosin IIA was significantly enhanced after bypass in high-dose group (3.729 ± 1.700 folds, P = .011) but not low-dose group (1.545 ± 0.595 folds, P = .076). Phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocyte membrane was also upregulated in high-dose group after bypass. Besides, plasma nitric oxide level was highly correlated with fold change of non-muscle myosin IIA phosphorylation (Pearson's correlation coefficient .871). CONCLUSIONS: High-dose nitroglycerin administered during cardiopulmonary bypass improves erythrocyte deformability through activating phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocytes.
Authors: John C Greenwood; David H Jang; Stephen D Hallisey; Jacob T Gutsche; Jiri Horak; Michael A Acker; Christian A Bermudez; Victoria L Zhou; Shampa Chatterjee; Frances S Shofer; Todd J Kilbaugh; John G T Augoustides; Nuala J Meyer; Jan Bakker; Benjamin S Abella Journal: J Cardiothorac Vasc Anesth Date: 2020-05-14 Impact factor: 2.628