Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease?

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose (DSC) column is commonly performed for extracorporeal removal of LDL in hypercholesterolemic patients with peripheral arterial obstructive disease. We investigated whether the use of heparin or nafamostat mesilate as anticoagulants in a single LDL apheresis produced different clinical effects, or brought about the production of bradykinin and endogenous nitric oxide (NO) in these patients. LDL apheresis was performed in ten patients with peripheral arterial obstructive disease. We measured plasma levels of bradykinin, NO and nitrosylhemoglobin as well as skin temperature. Plasma levels of bradykinin increased 12-fold during LDL apheresis with heparin, but did not increase during LDL apheresis with nafamostat mesilate. LDL adsorption resulted in an immediate rise in skin temperatures (1-2 degrees C) of the lower ischemic legs irrespective of the type of anticoagulant used, and this persisted after the end of LDL apheresis for up to 60 min. There was a progressive and significant increase in plasma NO after the commencement of single LDL apheresis in both groups (heparin group: 64.0 +/- 17.3 micromol/l at baseline, 73.3 +/- 15.2 micromol/l 60 min after apheresis, P<0.005; nafamostat mesilate group: 65.0 +/- 18.8 micromol/l at baseline, 75.5 +/- 17.5 micromol/l 60 min after apheresis, P<0.001). On the other hand, levels of nitrosylhemoglobin increased significantly after 1000 ml of plasma treatment but the level decreased thereafter, although it was significantly higher than baseline 60 min after LDL apheresis. Our results suggest that a single LDL apheresis enhanced peripheral microcirculation, probably as a result of increased production of NO, irrespective of changes in bradykinin release.