PMID- 12679132
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20201208
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 109
IP  - 1
DP  - 2003 Jan 1
TI  - Effects of argatroban and heparin on thrombus formation and tissue plasminogen 
      activator-induced thrombolysis in a microvascular thrombosis model.
PG  - 55-64
AB  - Effects of 
      (2R,4R)-4-methyl-1-[N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine-carboxylic 
      acid monohydrate (argatroban) and unfractionated heparin (UFH) were compared with 
      respect to thrombus formation and tissue-type plasminogen activator 
      (t-PA)-induced thrombolysis in a microvasculature thrombosis model. The 
      antithrombotic activities of anticoagulants were evaluated with respect to the 
      time required for the initiation of thrombus formation (T(i)) and the time 
      required for the thrombus to stop blood flow (T(s)). The effects of 
      anticoagulants administered with t-PA were evaluated by percent stenosis of the 
      vessel and percent area of the thrombus. Argatroban (1-3 mg/kg/bolus) 
      significantly prolonged T(i) and T(s) in a dose-dependent fashion compared to 
      control. Argatroban (3 mg/kg/bolus) significantly prolonged both the T(i) and 
      T(s) more effectively than UFH (100 anti-XaU (a-XaU)/kg/bolus), despite 
      equivalent prolongation of the activated partial thromboplastin time (aPTT). 
      Higher doses of UFH (300-500 a-XaU/kg) were required to significantly prolong 
      T(i) and T(s), but at these doses, UFH caused over-prolongation of aPTT (>180 s), 
      which might consequently cause bleeding complications. Argatroban (0.1-0.3 
      mg/kg/h) significantly accelerated thrombolysis by t-PA in both a dose- and 
      time-dependent fashion. Although argatroban (0.1-0.2 mg/kg/h) did not 
      significantly prolong the aPTT and bleeding time (BT) as compared with control, 
      it significantly accelerated thrombolysis by t-PA at these doses of lower 
      bleeding risk. Argatroban (0.3 mg/kg/h) significantly enhanced thrombolysis by 
      t-PA, while UFH (12.5 anti-XaU/kg/h) attenuated it again, despite equivalent 
      prolongation of the aPTT and BT. We conclude that argatroban seems to be a more 
      efficient and safer anticoagulant than UFH for the prevention of thrombus 
      formation and acceleration of t-PA-induced thrombolysis.
FAU - Yamada, Keizo
AU  - Yamada K
AD  - Second Department of Medicine, Kyoto Prefectural University of Medicine, 465 
      Kajii-cho Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan.
FAU - Tsuji, Hajime
AU  - Tsuji H
FAU - Kimura, Shinzo
AU  - Kimura S
FAU - Kato, Hisato
AU  - Kato H
FAU - Yano, Shingo
AU  - Yano S
FAU - Ukimura, Naoki
AU  - Ukimura N
FAU - Yamada, Yuka
AU  - Yamada Y
FAU - Nakagawa, Katsumi
AU  - Nakagawa K
FAU - Nakagawa, Masao
AU  - Nakagawa M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Pipecolic Acids)
RN  - 0 (Sulfonamides)
RN  - 9005-49-6 (Heparin)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - IY90U61Z3S (argatroban)
SB  - IM
MH  - Animals
MH  - Arginine/analogs & derivatives
MH  - Cricetinae
MH  - Disease Models, Animal
MH  - Drug Interactions
MH  - Fibrinolytic Agents/pharmacology
MH  - Heparin/administration & dosage/*pharmacology
MH  - Mesocricetus
MH  - Microcirculation/pathology
MH  - Partial Thromboplastin Time
MH  - Pipecolic Acids/administration & dosage/*pharmacology
MH  - Sulfonamides
MH  - Thrombolytic Therapy/*methods/standards
MH  - Thrombosis/*drug therapy
MH  - Time Factors
MH  - Tissue Plasminogen Activator/administration & dosage/*pharmacology
EDAT- 2003/04/08 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/04/08 05:00
PHST- 2003/04/08 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/04/08 05:00 [entrez]
AID - S0049384803001051 [pii]
AID - 10.1016/s0049-3848(03)00105-1 [doi]
PST - ppublish
SO  - Thromb Res. 2003 Jan 1;109(1):55-64. doi: 10.1016/s0049-3848(03)00105-1.