High-dose nitroglycerin administered during rewarming preserves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass

Microcirculation. 2020 May;27(4):e12608. doi: 10.1111/micc.12608. Epub 2020 Feb 13.

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 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.

Keywords: aquaporin 1; focal adhesion kinase; nitric oxide; non-muscle myosin IIA; vasodilator-stimulated phosphoprotein.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiac Surgical Procedures*
  • Cardiopulmonary Bypass*
  • Erythrocyte Deformability / drug effects*
  • Female
  • Humans
  • Hypothermia, Induced*
  • Male
  • Middle Aged
  • Nitroglycerin / administration & dosage*
  • Rewarming*
  • Vasodilator Agents / administration & dosage*

Substances

  • Vasodilator Agents
  • Nitroglycerin