Level and Effect of Adrenomedullin on Endotoxin Induced Disseminated Intravascular Coagulation Model in Rabbits

Adrenomedullin (ADM) is a regulatory peptide having a variety of pharmacological properties secreted from vascular endothelial cells and adrenal medulla. There are only a few studies about the effects of ADM on coagulation and platelets which is secreted from endothelial cells. The aim of this study is to assay ADM levels in rabbits with endotoxin induced disseminated intravascular coagulation (DIC) model and to investigate the probable effects of ADM on coagulation parameters in this model. Four groups (Control, DIC, Heparin, ADM) each consisting of eight New Zeland rabbits were formed randomly. A DIC model was developed by infusion of endotoxin from Escherichia coli. Then the effect of standard dose heparin and 0.05μg/kg/min ADM infusion were evaluated. Administration of endotoxin resulted in severe changes of coagulation parameters as shown by the significant prolongation of the prothrombin time and activated partial thromboplastin time, decrease in platelet count, plasma fibrinogen level, antithrombin, and protein C activity. These results were in accordance with DIC findings and were significantly different from baseline and control group. In DIC group, the baseline, second, and sixth hour mean ADM levels were 7.09±1.63, 8.10±1.55, 9.35±0.76 ng/dl, respectively. ADM levels on sixth hour were significantly higher than baseline and control group. Heparin and ADM were used in the DIC model but both of them were not effective. In conclusion, ADM levels were found elevated during the progress of endotoxin induced DIC model. ADM were not effective in overt DIC model but it might be useful in the early phase of the DIC.