ENHANCEMENT OF THE LEUKOCYTE-ENDOTHELIAL CELL-INTERACTION IN COLLECTING VENULES OF SKELETAL-MUSCLE BY PROTAMINE

Objective: A transient but severe systemic leukopenia regularly occurs after the antagonization of heparin by protamine in patients and in a nimals. The aim of the present study was to investigate the site and m echanisms of white blood cell retention during this transient leukopen ia by studying the leukocyte-endothelial cell interaction in skeletal muscle venules. Methods: Syrian golden hamsters were equipped with a d orsal skinfold chamber for intravital fluorescence microscopy and arte rial and venous catheters for drug infusion, blood pressure measuremen t, and blood sampling. Micro-hemodynamic parameters and leukocyte-endo thelial cell interactions were observed in one single collecting venul e per animal after intravenous infusion of saline solution (control, n = 10), of protamine (n = 9), and after infusion of heparin followed b y either intravenous protamine (n = 9) or intraarterial protamine (n = 9). Results: All parameters remained unchanged in the control group. Whereas venular diameters remained unchanged, protamine transiently in creased arterial blood pressure and venular erythrocyte velocity in al l groups. Systemic leukocyte counts and the venular leukocyte discharg e concentration decreased concurrently after protamine administration by about 60% to 70% at 2 minutes while the fraction of rolling leukocy tes and the number of adherent leukocytes remained unchanged. Two and one-half minutes later, systemic leukocyte counts and venular discharg e concentrations normalized while the fraction of leukocytes rolling s lowly along or adhering firmly to the venular endothelial wall increas ed considerably and similarly in all groups receiving protamine. Myelo peroxidase (an indicator of polymorphonuclear leukocytes) determinatio n in 20 separate hamsters 2 minutes after protamine infusion revealed increased myeloperoxidase activity exclusively in the lungs. Conclusio n: The response of leukocytes to protamine infusion with or without pr ior heparinization is biphasic: initial retention of leukocytes in the lungs is followed by enhanced leukocyte-endothelial cell interaction in the systemic circulation.