Dose-dependent effects of nitric oxide on erythrocyte membranes and platelet aggregation in an ex vivo model of cardiopulmonary bypass: an experimental study

INTRODUCTION: Delivering of exogenous nitric oxide (NO) into the extracorporeal circuit is a potential strategy for organ protection during cardiopulmonary bypass (CPB). However, its effects are dose-dependent, and optimal concentrations remain unclear. OBJECTIVE: To evaluate the dose-dependent effects of nitric oxide delivery on the structural and functional properties of erythrocyte membranes and platelet aggregation activity in an ex vivo model of CPB. MATERIALS AND METHODS: We performed a single-center, prospective, pilot, experimental ex vivo study using a CPB model. Whole blood samples were obtained from eight healthy volunteers. CPB was simulated for 60 minutes under five conditions: a control (no NO) and NO delivery at 40, 80, 120, and 160 ppm. Erythrocyte membrane microviscosity and polarity were assessed, alongside spontaneous and induced platelet aggregation (adenosine diphosphate, collagen, epinephrine, arachidonic acid). RESULTS: In the control group, 60 minutes of CPB simulation significantly increased erythrocyte membrane microviscosity and decreased membrane polarity. NO delivery in the range of 40–120 ppm prevented the development of these changes. However, an NO concentration of 160 ppm increased the microviscosity of lipid–lipid interactions in erythrocyte membranes. In the control group, collagen-and low-dose of adenosine diphosphate-induced platelet aggregation decreased during CPB simulation. While NO administration at 40–120 ppm stabilized platelet aggregation activity, a concentration of 160 ppm enhanced collagen-induced platelet aggregation. CONCLUSIONS: Exogenous nitric oxide exerts dose-dependent effects on the structural and functional properties of erythrocyte membranes and platelet aggregation activity in an ex vivo CPB model. Nitric oxide concentrations of 40–120 ppm exert membrane-stabilizing effects and prevent platelet hyperactivation, whereas further dose escalation leads to a loss of protective properties.