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

Abstract

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.

Blood Flow Analysis of the Head and Lower Limbs by the Laser Doppler Blood Flowmeter During LDL Apheresis

“…Moreover, during LDL apheresis, the generation of bradykinin and increased plasma levels of NO were observed in peripheral atherosclerosis patients (13). Bradykinin generated during apheresis has some pathophysiological effects via activation of the prostaglandin system because the plasma levels of prostaglandin E 2 increased significantly in association with an increase in bradykinin levels during apheresis (14). In those studies, although vasoreactive mediators such as NO, bradykinin, or prostaglandin were measured, actual monitoring of the peripheral circulation were not examined.…”

Treatment of homozygous familial hypercholesterolemia

“…This may not be a disadvantage as pre-b HDL rapidly accumulates after the procedure. Apheresis procedures are all equally well tolerated but the polymer adsorption techniques have the disadvantage of releasing bradykinin owing to platelet contact with the medium, which requires discontinuation of ACE inhibitors [63,64]. DMPP has the advantage, like plasma exchange, that the equipment can be used with different filters for a variety of purposes with cost benefits.…”

Bradykinin metabolism and hypotensive transfusion reactions

“…During LDL apheresis, LDL cholesterol is adsorbed to low‐molecular‐weight dextran sulfate covalently bound to cellulose on the columns. Some patients taking ACE inhibitors experienced hypotension, erythematous skin (particularly on the face and neck), bradycardia, nausea, and sometimes other symptoms such as dyspnea, sweats, headache, and abdominal pain 103–111 . These symptoms started shortly after the treated plasma was returned to the patient and subsided within minutes of discontinuing the transfusion.…”