PMID- 7678610
OWN - NLM
STAT- MEDLINE
DCOM- 19930224
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 91
IP  - 1
DP  - 1993 Jan
TI  - The contact system contributes to hypotension but not disseminated intravascular 
      coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII 
      antibody to block contact activation in baboons.
PG  - 61-8
AB  - The hypotension and disseminated intravascular coagulation (DIC) in bacteremia is 
      thought to be mediated by the combined actions of cytokines, prostaglandins, and 
      complement. The contact system, via the release of bradykinin and the activation 
      of Factor XI, has been postulated to be contributing to the observed hypotension 
      and DIC. Using a mAb to Factor XII (C6B7), we blocked the activation of the 
      contact system in an established experimental baboon model in which Escherichia 
      coli was infused to produce lethal bacteremia with hypotension. The untreated 
      group (n = 5) displayed contact activation, manifested by a significant decrease 
      in high molecular weight kininogen (HK) and a significant increase in alpha 2 
      macroglobulin-kallikrein complexes (alpha 2M-Kal). The C6B7-treated group (n = 5) 
      showed an inactivation of Factor XII and the changes in HK and alpha 2M-Kal 
      complexes were prevented. Both groups developed DIC manifested by a decrease in 
      platelet, fibrinogen, and Factor V levels. The untreated group developed 
      irreversible hypotension. The treated group experienced an initial hypotension 
      that was reversed and extended the life of the animals. This study suggests that 
      irreversible hypotension correlates with prolonged activation of the contact 
      system, and specific antibody therapy can modulate both the pathophysiological 
      and biochemical changes.
FAU - Pixley, R A
AU  - Pixley RA
AD  - Thrombosis Research Center, Temple University School of Medicine, Philadelphia, 
      Pennsylvania 19140.
FAU - De La Cadena, R
AU  - De La Cadena R
FAU - Page, J D
AU  - Page JD
FAU - Kaufman, N
AU  - Kaufman N
FAU - Wyshock, E G
AU  - Wyshock EG
FAU - Chang, A
AU  - Chang A
FAU - Taylor, F B Jr
AU  - Taylor FB Jr
FAU - Colman, R W
AU  - Colman RW
LA  - eng
GR  - HL07828/HL/NHLBI NIH HHS/United States
GR  - HL36579/HL/NHLBI NIH HHS/United States
GR  - S07RR05417/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Kininogens)
RN  - 0 (alpha-Macroglobulins)
RN  - 9001-30-3 (Factor XII)
RN  - 9001-32-5 (Fibrinogen)
RN  - EC 3.4.21.- (Kallikreins)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Bacteremia/*blood/*physiopathology
MH  - Blood Pressure
MH  - Disseminated Intravascular Coagulation/*physiopathology
MH  - Escherichia coli Infections/*blood/*physiopathology
MH  - Factor XII/antagonists & inhibitors/immunology/*physiology
MH  - Fibrinogen/*metabolism
MH  - Heart Rate
MH  - Humans
MH  - Hypotension/*etiology
MH  - Kallikreins/*metabolism
MH  - Kinetics
MH  - Kininogens/*metabolism
MH  - Papio
MH  - Platelet Count
MH  - alpha-Macroglobulins/*metabolism
PMC - PMC329995
EDAT- 1993/01/01 00:00
MHDA- 2001/03/28 10:01
PMCR- 1993/01/01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
PHST- 1993/01/01 00:00 [pmc-release]
AID - 10.1172/JCI116201 [doi]
PST - ppublish
SO  - J Clin Invest. 1993 Jan;91(1):61-8. doi: 10.1172/JCI116201.