Effect of propranolol on epinephrine-induced SS RBC adhesion and organ sequestration. (A) β- and β2-AR antagonists abolish epi-induced SS RBC adhesion to HUVECs in vitro at a shear stress of 2 dynes/cm2. SS RBCs were sham treated, epi treated, or pretreated with phenoxybenzamine, propranolol, atenolol, or butoxamine followed by treatment with epi (n = 3 each). Error bars show SEM of 3 different experiments. *P < .01 compared with sham-treated; **P < .001 compared with epi-treated. (B) In vitro propranolol treatment had no effect on SS RBC adhesion (n = 5) in vivo, whereas epi dramatically increased SS RBC adhesion and vaso-occlusion to venule walls (n = 5). Propranolol treatment of SS RBCs significantly reduced subsequent epi-stimulated adhesion and stasis (n = 5). (C) Effect of propranolol on percent venular length occupied by SS RBCs. Video frames showing more than 30 vessel segments were used to quantify the length of venules occupied by SS RBCs in animals infused with SS RBCs treated as described for panel A (n = 5 for each treatment). The values were averaged among groups of animals to represent the mean percent venular length occupied by SS RBCs. Error bars show SEM. *P < .01 compared with propranolol-treated RBCs for vessels up to 25 μm in diameter, and P < .001 for vessels more than 25 μm in diameter. **P < .01 compared with epi-treated RBCs regardless of the vessel diameter. (D-E) SS RBCs were epi treated or propranolol + epi treated. Epi-treated SS RBCs were extensively trapped in the lung and spleen. Propranolol significantly reduced epi-treated SS RBC trapping in the lung and spleen. SS RBC trapping in the kidney was similar for all cell preparations. Error bars show SEM of 5 different experiments. *P < .05 compared with sham-treated (not pictured); **P < .05 compared with epi-treated. Scale bar = 100 μm.
