Abnormal erythrocyte endothelial adherence in ischemic heart disease

Abstract

While the mechanism of platelet and more recently leukocyte interactions with vessel walls in heart disease have been extensively studied, the phenomenon of red cell binding to endothelium in this condition has not been previously described. To test the hypothesis that erythrocyte endothelial cell adherence may be an important component of flow disturbance in patients with myocardial injury venous blood from 31 patients admitted with chest pain suggestive of myocardial infarction or ischemia was compared to blood from acutely ill patients without ischemic injury and normal controls. Red cells separated from white cells and platelets were allowed to adhere to endothelial cells grown in culture from human umbilical cord veins. Shear force ranging from 0.1 to 55 dynes/cm² was applied by calibrated fluid flow through a micropipette. Direct visualization by microscope, allowed precise measurement of the stress required to separate individual red cells from the endothelial cell monolayer. In those patients who had documented ischemic damage adherence ranged from 1.3% of red blood cells at 20 dynes/cm² (the approximate maximum shear stress in venules) to 0.01% RBC at 55 dynes/cm², (maximum shear stress in arterioles). In control samples and in hospital patients without documented ischemia, 0.55% cells adhered at 20 dynes/cm² and less than 0.01% adhered at 55 dynes/cm². Autologous plasma increased the percent of maximally adherent cells to 21.9% in patients with unstable angina compared to 1.5% in patients without documented ischemia. Some adherent red cells that separated from the endothelium while under fluid flow conditions, immediately reattached to adjacent endothelial cells, implying that only brief contact is required for adherence to occur. We conclude that in areas of the microcirculation where erythrocyte-endothelial cell contact occurs, abnormal adherence may compromise blood flow and contribute to ischemic injury in some patients with ischemic heart disease.