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Sökning: swepub > Larsson Anders > Tidskriftsartikel > Eriksson Mats > Eriksson Örjan > Effects of melagatr...

  • Basu, SamarUppsala universitet,Institutionen för folkhälso- och vårdvetenskap (författare)

Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock

  • Artikel/kapitelEngelska2000

Förlag, utgivningsår, omfång ...

  • 2005-02-24
  • Informa Healthcare,2000
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-63002
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-63002URI
  • https://doi.org/10.1517/13543784.9.5.1129DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

Ämnesord och genrebeteckningar

  • MEDICINE
  • MEDICIN

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Larsson, AndersUppsala universitet,Anestesiologi och intensivvård(Swepub:uu)andla606 (författare)
  • Mattsson, Christer (författare)
  • Eriksson, Örjan (författare)
  • Kiiski, RitvaUppsala universitet,Institutionen för kirurgiska vetenskaper,Anaesthesiology and Intensive Care (författare)
  • Nordgren, AndersUppsala universitet,Anestesiologi och intensivvård,Anaesthesiology and Intensive Care(Swepub:uu)andnord (författare)
  • Eriksson, MatsUppsala universitet,Anestesiologi och intensivvård(Swepub:uu)matserik (författare)
  • Uppsala universitetInstitutionen för folkhälso- och vårdvetenskap (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Expert Opinion on Investigational Drugs: Informa Healthcare9:5, s. 1129-11371354-37841744-7658

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