Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation.
BACKGROUND
Tissue factor (TF), the main trigger of coagulation is important in the propagation of cardiovascular diseases. Based on an in vitro study, we hypothesised that enalapril may blunt the endotoxin-induced, TF-triggered coagulation in humans.


METHODS
In a randomised, controlled trial, 30 healthy male volunteers received 2 ng/kg of lipopolysaccharide (LPS) after pre-treatment with placebo or enalapril for 5 days or with enalapril 2 h before LPS infusion.


RESULTS
Infusion of LPS increased interleukin-6 levels 400 fold, and induced a 10-fold increase in prothrombin fragment, a fourfold increase in D-dimer, and a fivefold increase in plasmin-antiplasmin complexes. However, pre-treatment with enalapril did not blunt LPS-induced coagulation.


CONCLUSIONS
Our trial provides evidence against a modulatory role of angiotensin converting enzyme in LPS-induced, TF-triggered coagulation.
Marsik
Claudia
C
Department of Clinical Pharmacology, Vienna University, Vienna, Austria. bernd.jilma@univie.ac.at
Graninger
Monika
M
Mackman
Nigel
N
Osterud
Bjarne
B
Luther
Thomas
T
Jilma
Bernd
B
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004656:Enalapril / Q000627:therapeutic use*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D011516:Prothrombin / Q000032:analysis; D018709:Statistics, Nonparametric; D013925:Thromboplastin / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D008070:Lipopolysaccharides; C036309:fibrin fragment D; D004656:Enalapril; D011516:Prothrombin; D013925:Thromboplastin; D005341:Fibrinolysin