Linked Life Data

10595641

Source:http://linkedlifedata.com/resource/pubmed/id/10595641

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-2-14
pubmed:abstractText
Investigations were performed to characterize a recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor (rKPI) as anticoagulants. After a single intravenous infusion of wild type rKPI into dogs, its elimination fit a two compartment model with a t1/2alpha and t1/2beta of 5 and 77 min, respectively. Further investigations determined if a variant form of rKPI with 178-fold more potent anti-factor Xa activity (rKPI-DD135, Ki = 0.9 nM) could serve as an anticoagulant in a rabbit model of extracorporeal circulation using a venovenous shunt. A prospective investigation was initiated to compare standard heparin (n = 8) at 400 U/kg with different infusion concentrations of rKPI-DD135. After a single intravenous infusion of 1.89 mg/kg of rKPI-DD135 followed by a constant infusion at 0.003 (n = 3), 0.03 (n = 7), or 0.3 (n = 5) mg/kg/min, the anti-factor Xa activity of the animals' plasma rapidly reaches a steady state for the two lower infusion concentrations of the agent. All infusions of rKPI-DD135 prolong the activated clotting time with less variation than that seen with heparin administration. rKPI-DD135 anticoagulation does not prevent a drop in the platelet counts. Fibrinogen levels decrease only slightly when the circuit is anticoagulated with rKPI-DD135. rKPI-DD135 markedly prolongs the APTT, has little effect on the PT, and reduces plasma prekallikrein and plasminogen activation. The 0.3 mg/kg/min infusion concentration of rKPI-DD135 results in reduced deposition of 111Indium-labeled platelets on the circuit when compared to heparin. Last, after a steady state level is achieved, 60% of the plasma anti-factor Xa activity of rKPI-DD135 is eliminated within 60 min after stopping the infusion. These data show the rKPI-DD135 can provide single agent anticoagulation in a rabbit extracorporeal circuit. Development of short acting factor Xa inhibitors may be useful anticoagulants for cardiopulmonary bypass.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1474-81
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor as an anticoagulant in venovenous extracorporeal circulation in rabbits.
pubmed:affiliation
Department of Pediatrics, University of Michigan, Ann Arbor 48109-0640, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't