PMID- 20806115
OWN - NLM
STAT- MEDLINE
DCOM- 20110408
LR  - 20201209
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 104
IP  - 5
DP  - 2010 Nov
TI  - Argatroban administration reduces leukocyte adhesion and improves capillary 
      perfusion within the intestinal microcirculation in experimental sepsis.
PG  - 1022-8
LID - 10.1160/TH10-04-0241 [doi]
AB  - Co-activation of pro-coagulatory pathways in sepsis may result in disseminated 
      intravascular coagulation and contributes to microvascular dysfunction. We 
      investigated the effects of the direct thrombin inhibitor, argatroban (ARG), on 
      the sepsis-induced impairment of the intestinal microcirculation (capillary 
      perfusion, leukocyte adhesion) and the vascular contractility in rats. Forty male 
      Lewis rats were randomly assigned to one of four groups: sham surgery (SHAM), 
      experimental sepsis (colon ascendens stent peritonitis--CASP), CASP+ARG, and 
      SHAM+ARG. At 16 hours after colon stent insertion (or sham surgery), 2 mg/kg 
      argatroban or buffer were given intravenously, and 1 hour thereafter, intravital 
      microscopy was performed. In addition, experiments to study the impact of ARG on 
      vascular contractility were conducted in vitro . ARG administration in CASP rats 
      significantly increased functional capillary density in mucosal (+128%) and 
      muscular layers (longitudinal: +42%; circular: +64%) and decreased the number of 
      firmly adhering leukocytes in the intestinal submucosa compared to untreated 
      animals. In vitro findings indicated a vasodilating effect of ARG. ARG 
      administration during experimental sepsis improved intestinal microcirculation by 
      preserving functional capillary density, an indicator of microvascular perfusion, 
      and by reducing leukocyte adherence to the endothelium in submucosal venules.
FAU - Fuchs, Christian
AU  - Fuchs C
AD  - Department of Anesthesia and Intensive Care Medicine, 
      Ernst-Moritz-Arndt-Universitat, Greifswald, Germany.
FAU - Ladwig, Elena
AU  - Ladwig E
FAU - Zhou, Juan
AU  - Zhou J
FAU - Pavlovic, Dragan
AU  - Pavlovic D
FAU - Behrend, Kristina
AU  - Behrend K
FAU - Whynot, Sara
AU  - Whynot S
FAU - Hung, Orlando
AU  - Hung O
FAU - Murphy, Michael
AU  - Murphy M
FAU - Cerny, Vladimir
AU  - Cerny V
FAU - Lehmann, Christian
AU  - Lehmann C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100830
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Pipecolic Acids)
RN  - 0 (Sulfonamides)
RN  - 94ZLA3W45F (Arginine)
RN  - IY90U61Z3S (argatroban)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Arginine/analogs & derivatives
MH  - Blood Pressure/drug effects
MH  - Capillaries/*drug effects/immunology/physiopathology
MH  - Cell Adhesion/*drug effects
MH  - Disease Models, Animal
MH  - Heart Rate/drug effects
MH  - Intestines/*blood supply
MH  - Leukocytes/*drug effects/immunology
MH  - Male
MH  - Microcirculation/*drug effects
MH  - Microscopy, Video
MH  - Myography
MH  - Pipecolic Acids/*pharmacology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Sepsis/*drug therapy/immunology/physiopathology
MH  - Splanchnic Circulation/*drug effects
MH  - Sulfonamides
MH  - Time Factors
MH  - Vasodilation/drug effects
EDAT- 2010/09/02 06:00
MHDA- 2011/04/09 06:00
CRDT- 2010/09/01 06:00
PHST- 2010/04/20 00:00 [received]
PHST- 2010/07/19 00:00 [accepted]
PHST- 2010/09/01 06:00 [entrez]
PHST- 2010/09/02 06:00 [pubmed]
PHST- 2011/04/09 06:00 [medline]
AID - 10-04-0241 [pii]
AID - 10.1160/TH10-04-0241 [doi]
PST - ppublish
SO  - Thromb Haemost. 2010 Nov;104(5):1022-8. doi: 10.1160/TH10-04-0241. Epub 2010 Aug 
      30.