The role of shear forces in ischemia/reperfusion-induced neutrophil rolling and adhesion

Intravital microscopy was used to examine the role of reduced shear forces on neutrophil-endothelium interactions in single 25-40 microm diameter vessels in the feline postischemic mesenteric microvasculature. Neutrophil rolling, neutrophil adhesion, and microvascular permeability alterations were determined in vessels exposed to ischemia/reperfusion in untreated animals and in cats that received feline plasma directly into the superior mesenteric artery to increase intestinal blood flow and venular shear rates. Ischemia, followed by reperfusion, caused a profound increase in venular shear forces during the initial hyperemic response, which then decreased to below control values by 10 min of reperfusion and to less than 50% of control by 60 min of reperfusion. Associated with the decrease in blood flow was a profound increase in neutrophil rolling and neutrophil adhesion and an increase in microvascular permeability. Also, leukocyte rolling velocity decreased dramatically to 10-20% of control values during the first 10 min of reperfusion. Infusion of autologous plasma into the intestinal vasculature to maintain the shear forces at control levels during reperfusion did not affect the flux of rolling neutrophils. The rolling velocity of the neutrophils was not increased despite dramatically improved shear rates. Improved shear rates did reduce the number of adherent cells, resulting in less vascular dysfunction. The reduction in shear forces through inflamed microvessels does not contribute to the increased leukocyte rolling flux but is an essential, permissive component for neutrophil adhesion and subsequent vascular dysfunction in postischemic microvasculature.