Pathogenic Role Of Thrombus Formation In The Microcirculation Of Mucosa In The Gastrointestinal Defence Mechanism

Abstract

There is no doubt that impaired blood supply to the gastrointestinal (GI) tract causes various pathological changes in the digestive mucosa by disrupting the defence mechanism. Ischemic change of the intestinal mucosa is classified into (1) occlusive mesenteric ischemia and (2) non-occlusive mesenteric ischemia, and intravascular clot formation has been investigated mainly in the former category.However, GI-bleeding of unknown origin is often experienced during the management of patients in disseminated intravascular coagulation (DIC), while to which neither the mechanism nor the specific treatment has been indicated. In the present study, the role of the microcirculation in the GI- defence mechanism is investigated from the standpoint of DIC.Single injection of E. coli endotoxin to dogs resulted in hemorrhagic necrosis of the GI mucosa within 8 hrs, and this was prominent in the small intestine where hemorrhagic change started at the top of villi. Microscopic examination showed tortuous thrombus formation in the microcirculation of the mucosa.When the jejunal mucosa was treated directly by protease inhibitors such as tranexamic acid or aprotinin prior to endotoxin, hemorrhagic necrosis of the area was successfully prevented, suggesting that proteolytic enzymes either in the GI-cavity or in the tissue digested the ischemic mucosa.Systemic pretreatment of rats with heparin was effective in preventing the hemorrhagic necrosis, strongly indicated that blood supply to the microcirculation of the GI-mucosa played a role in the GI-defence mechanism.It is concluded that in the managing patients with DIC, one should be careful to protect GI-bleeding which often appear in the form of hemorrhagic necrosis. Besides the use of systemic anticoagulants, direct contact of protease inhibitors with GI-mucosa might be of help in the protection or the treatment of GI-bleeding in DIC.