カワシマ アキツグ   Kawashima Akitsugu
  川島 明次
   所属   医学部 医学科(東京女子医科大学病院)
   職種   准教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Carotid tissue levels of argatroban after direct local delivery during carotid endarterectomy to prevent perioperative cerebral embolism.
掲載誌名 正式名:Neurosurgery
略  称:Neurosurgery
ISSNコード:15244040/0148396X
掲載区分国外
巻・号・頁 56(5),pp.913-8-discussion 913-8
著者・共著者 Kawamata Takakazu, Okada Yoshikazu, Kawashima Akitsugu, Hori Tomokatsu
発行年月 2005/05
概要 OBJECTIVE:Argatroban is a synthetic direct thrombin inhibitor. We applied argatroban locally during carotid endarterectomy to prevent local mural thrombus formation. Although local delivery of argatroban is expected to be effective for inhibition of mural clot formation, there is no report of the evaluation of its clinical effectiveness or local drug concentration in humans.METHODS:Five mg of argatroban (0.5 mg/ml) was applied twice intraoperatively just after arteriotomy for measurement of intraplaque level of argatroban and during closure of the arteriotomy for preventing thrombus formation. After exposure of the carotid plaque to argatroban for a specified duration (0, 3, 5, or 10 min), argatroban was sufficiently washed with saline and the carotid plaque was removed for measurement of tissue concentration of argatroban. Intraplaque level of argatroban was determined by high-performance liquid chromatography. A second application was performed during closure of the arteriotomy. Argatroban was applied for 10 minutes, followed by washing with saline. Postoperative embolic cerebrovascular complications and carotid restenosis also were investigated to verify the efficacy of direct local application of argatroban.RESULTS:Tissue levels of argatroban in the carotid plaque after 3, 5, and 10 minutes of direct application were 24.0 +/- 13.7, 31.6 +/- 20.0, and 44.0 +/- 15.1 mug/g, respectively. The concentrations at all time points were significantly elevated compared with the control, and a significant difference in concentration was observed between 3 minutes and 10 minutes. In the present study, concentration at 3 minutes was much higher than the effective tissue levels of argatroban reported in experimental studies. No patient developed postoperative cerebrovascular complications.CONCLUSION:The results suggest that direct local application of argatroban during carotid endarterectomy for at least 3 minutes may deliver high local tissue levels. Argatroban may be effecti
DOI 10.1227/01.NEU.0000157924.59637.3A
PMID 15854238