Background/Objectives: Cardiopulmonary bypass (CPB) facilitates complex cardiac surgery but can damage erythrocyte membranes, impairing microcirculation and oxygen transport. Standard rheological tests assess overall blood properties but fail to define specific cellular mechanisms. In this study, atomic force microscopy (AFM) was employed to characterize morphological, nanostructural, and mechanical changes in erythrocytes following CPB and CPB combined with hypothermic circulatory arrest (HCA). 

Methods: The study included 14 patients who underwent cardiac surgery with CPB. Patients were divided into two groups. Group 1 underwent heart valve surgery with normothermic CPB (n = 7), and Group 2 underwent aortic arch surgery with CPB combined with HCA and moderate hypothermia (28 °C) (n = 7). Arterial blood samples were collected before the induction of anesthesia and immediately after CPB. The morphology and surface roughness (Rtm) of the erythrocyte membrane were evaluated on air-dried blood smears. Young’s modulus (E) was estimated from force-distance curves on living cells; measurements were performed at 24 °C in PBS. 

Results: Following CPB, both groups exhibited a decrease in the proportion of discocytes and an increase in echinocytes. In the CPB+HCA group, discocytes were absent after surgery. The mean Rtm increased 1.4-fold in Group 1 and 1.6-fold in Group 2, indicating greater nanostructural membrane damage in the latter. In Group 1, Young’s modulus increased by an average of 1.6 times, indicating increased cell stiffness. In Group 2, the increase was smaller (mean: 1.1 times) and was not statistically significant in some patients. 

Conclusions: Normothermic CPB primarily affects the nanomechanical properties of erythrocytes, whereas CPB+HCA induces more severe morphological and membrane surface damage while relatively preserving cytoskeletal elasticity. AFM-derived parameters of membrane roughness and cell elasticity may serve as sensitive indicators of erythrocyte biophysical integrity.