Changes in Bradykinin and Prostaglandins Plasma Levels during Dextran-sulfate Low-density-lipoprotein Apheresis

The negative charges of dextran-sulfate (DS) used for low-density-lipoprotein (LDL) apheresis initiate the intrinsic coagulation pathway in which plasma kallikrein acts on the high-molecular-weight kininogen to produce large amounts of bradykinin. This study was undertaken to assess whether bradykinin generated during DS LDL apheresis has any physiologic effects in vivo. The plasma levels of bradykinin, prostaglandins and cyclic guanosine monophosphate (cGMP) were compared, when either of two anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the plasma levels of prostaglandin E₂ (PGE₂) increased significantly (5.6 ± 1.2 (mean ± SE, n=4) pg/ml before apheresis and 33.4 ± 13.2 after apheresis, p < 0.05) in association with an increase in bradykinin levels (17.9 ± 2.6 pg/ml before apheresis and 470 ± 135 after apheresis, p < 0.01). Interestingly, these changes were suppressed during apheresis using NM. There were no appreciable changes in cGMP during DS LDL apheresis with either of the anticoagulants. This finding suggests that bradykinin generated during apheresis has some pathophysiological effects via activation of the prostaglandin system. Our results support the view that in patients taking angiotensin-convertingenzyme inhibitors, the anaphylactoid reaction occurring during apheresis may be caused by an excessive rise in the bradykinin levels.