Melagatran, a Low Molecular Weight Thrombin Inhibitor, Counteracts Endotoxin-induced Haemodynamic and Renal Dysfunctions in the Pig

Mats Eriksson; Anders Larsson; Tom Saldeen; Christer Mattsson

doi:10.1055/s-0037-1615405

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(06): 1022-1026
DOI: 10.1055/s-0037-1615405

Letters to the Editor

Schattauer GmbH

Melagatran, a Low Molecular Weight Thrombin Inhibitor, Counteracts Endotoxin-induced Haemodynamic and Renal Dysfunctions in the Pig

Mats Eriksson

¹Departments of Anaesthesiology and Intensive Care

,

Anders Larsson

²Clinical Chemistry

,

Tom Saldeen

³Forensic Medicine, University Hospital, Uppsala

,

Christer Mattsson

⁴Astra Hässle Preclinical Research and Development, Mölndal, Sweden

› Institutsangaben

Abstract

Summary

Coagulation and fibrinolysis are crucial in septic shock and inhibition of thrombin may be beneficial in this circumstance. Since porcine endotoxaemia has been found to replicate severe septic shock, a low molecular weight thrombin inhibitor, melagatran, was infused during the first 3 out of 6 h of endotoxaemia in pigs. Plasma creatinine (p <0.01) and urinary output (p <0.05) were less affected in the melagatran + endotoxin group (n = 6) as compared to endotoxaemic controls (n = 9). The left ventricular stroke work index, systemic vascular resistance index and oxygen extraction were all less affected (p <0.05) by endotoxin during the infusion of melagatran. The plasma concentration of melagatran declined with an apparent plasma half-life of 5 h as soon as the infusion was stopped. APTT, however, continued to increase after the infusion of melagatran had stopped and reached a maximum of 113 s at 5 h (baseline 17 s). APTT in endotoxaemic control pigs reached a maximum of 22 s. Thus, melagatran may counteract some consequences of endotoxaemia.

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Referenzen

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