title: Argatroban increases nitric oxide levels in patients with peripheral arterial obstructive disease: placebo-controlled study.
abstract: Intravenous argatroban infusion therapy is widely used for the restoration of peripheral microcirculation in patients with peripheral arterial obstructive disease (PAOD). We investigated the effect of argatroban infusion therapy on plasma levels of nitric oxide (NO) and nitrosylhemoglobin (HbNO) in patients with PAOD compared with a placebo-treated PAOD group. The chemiluminescence method was used to determine plasma NO and HbNO. Argatroban was administered as a continuous intravenous infusion for 60 minutes and repeated daily over a period of 2 weeks in 10 patients with PAOD. Treatment significantly improved the clinical signs and symptoms. Serial thermograms showed a 1-2 degrees C rise in the temperature of the affected legs in all patients immediately after intravenous argatroban infusion therapy. Enhancement of the peripheral circulation was maintained after the end of argatroban infusion for up to 90 minutes despite elimination of argatroban from the circulation. Furthermore, there was a progressive and significant increase in the mean concentration of plasma NO in PAOD patients after commencement of argatroban infusion (baseline, 58.0 +/- 13. 7;90 minutes after infusion, 65.7 +/- 13.4 microM; P < 0.01). HbNO significantly increased from a baseline value of 1063 +/- 126 to 1460 +/- 250 nM at 30 minutes after infusion (P < 0.01). However, the level of HbNo decreased thereafter, although it remained significantly elevated, even at 90 minutes after the end of argatroban infusion. Our results suggest that argatroban may lead to increased HbNO and plasma NO, and this may contribute to the improved microcirculation in PAOD patients.
authors.affiliation: Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ueki
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kizaki
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: S
authors.initials: S
authors.lastname: Miyake
authors.forename: Y
authors.initials: Y
authors.lastname: Tominaga
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D010875:Pipecolic Acids / Q000008:administration & dosage*; D013449:Sulfonamides
chemical_list: D000925:Anticoagulants; D006454:Hemoglobins; D010875:Pipecolic Acids; D013449:Sulfonamides; C008657:nitrosyl hemoglobin; D009569:Nitric Oxide; D001120:Arginine; C031942:argatroban