fibrin and Mesenteric-Vascular-Occlusion

To increase the survival rate of patients with acute superior mesenteric artery thromboembolism (ASMAT) treated by catheter thrombolysis, we examined the effects of delivering edaravone and asialoerythropoietin, agents with tissue-protective activities, using a rabbit autologous fibrin clot ASMAT model. Japanese white rabbits (n=32) were randomly separated into four equal groups. 45 min after introducing autologous fibrin clot, Group U received urokinase and heparin; Group E received urokinase and heparin plus edaravone; Group A received urokinase and heparin plus asialoerythropoietin; and Group EA received urokinase, heparin and edaravone plus asialoerythropoietin via a catheter. The intestines were removed 6 h later and intestinal mucosal damage was scored using the Park's injury score. Survival time was assessed. Average mucosal injury was 5.78+/-1.52 (Group U), 2.88+/-0.72 (Group E), 1.90+/-1.23 (Group A) and 1.18+/-1.25 (Group EA). The degree of mucosal injury was significantly lower in Group EA than in Groups U and E (p<0.05). Conversely, there was no significant difference between Group A and Group EA, or between Group A and Group E. The survival times were 31.50+/-13.30 h (Group U), 51.00+/-24.74 h (Group E), 48.00+/-16.97 h (Group A) and 82+/-51.07 h (Group EA); the difference among the four groups was not significant. In conclusion, the concomitant administration of asialoerythropoietin and edaravone reduced mucosal membrane injury significantly compared with edaravone alone. However, to improve the survival of ASMAT rabbit models, the delivery of an appropriate dose of asialoerythropoietin is required, together with the development of methods to assess peripheral recanalisation.

Topics: Animals; Antipyrine; Asialoglycoproteins; Catheterization; Disease Models, Animal; Drug Combinations; Edaravone; Erythropoietin; Fibrin; Fibrinolytic Agents; Free Radical Scavengers; Heparin; Injections, Intra-Arterial; Intestinal Mucosa; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Rabbits; Random Allocation; Reperfusion Injury; Survival Rate; Thromboembolism; Urokinase-Type Plasminogen Activator

We previously described a model of laser-induced thrombosis in mesenteric arterioles with superficial and deep levels of injury producing a transient thrombus resolving within 2 min and a larger almost occlusive thrombus, respectively. Both types of lesion were sensitive to platelet GPIIb-IIIa and P2Y(12) inhibition, whereas only deep injuries were sensitive to thrombin blockade.. The aim of the present study was to use histologic methods and electron and intravital microscopy to characterize the lesions and thrombi and to extend our knowledge of the sensitivity of this model to genetic and pharmacologic inhibition.. A superficial injury was found to detach the endothelial cells and expose a collagen III- and IV-rich subendothelium where platelets could adhere. Tissue factor and fibrin were not detected. Deeper penetration of the external elastic lamina occurred in deep injuries, with exposure of collagen I, III and IV. Here the thrombus was composed of platelets exhibiting a decreasing gradient of degranulation from the deepest lesion area to the surface. Fibrin was found close to the most activated platelets. Consistently, glycoprotein VI (GPVI)-collagen and GPIb-von Willebrand factor (VWF) interactions were found to be critical in superficial injuries. After deep lesion, thrombus formation was modestly reduced in GPVI-immunodepleted mice and still strongly inhibited in VWF(-/-) mice. Combined hirudin infusion and GPVI depletion further inhibited thrombosis after deep injury.. This study confirms the feasibility of inducing arterial thrombosis with distinct levels of severity and establishes the central roles of collagen and VWF in thrombus formation after superficial injury. Collagen, VWF and thrombin all appear to contribute to thrombosis after deep arterial lesion.

Topics: Animals; Blood Platelets; Collagen Type I; Collagen Type III; Collagen Type IV; Disease Models, Animal; Endothelium, Vascular; Feasibility Studies; Fibrin; Fibrinolytic Agents; Hirudins; Injections, Subcutaneous; Lasers, Gas; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Mice; Mice, Knockout; Platelet Adhesiveness; Platelet Membrane Glycoproteins; Severity of Illness Index; Thrombosis; Time Factors; von Willebrand Factor

The aim of this study was to evaluate the effects of intra-arterial administration of edaravone after superior mesenteric artery (SMA) thromboembolism in a rabbit model. 24 Japanese white rabbits were randomly allocated to a urokinase group (group U) and a urokinase with edaravone group (group E). A further three rabbits, which were administered an autologous blood clot alone, served as a control group (group C). A 4-Fr sheath was inserted into an SMA. An autologous blood clot was administered to an SMA (group C). After 45 min, urokinase (6000 IU) and heparin (250 IU) were administered through the catheter, either alone (group U) or in conjuction with edaravone (0.5 mg kg(-1)) (group E). In eight rabbits from each of groups U and E, 6 h after reperfusion, the small intestine was harvested and divided into five equal parts. The degree of intestinal tissue injury in each part was rated on a scale of 0-8. After 1 week, survival times and blood biochemistry data were compared among rabbits in group U (four rabbits), group E (four rabbits) and group C (three rabbits), and significant differences (p<0.05) were recorded. Intestinal mucosal damage was significantly greater in group U (5.8 +/- 1.5) than in group E (2.9 +/- 0.7). Survival time tended to be longer in group E (p>0.4, not significant compared with group U). Liver and kidney function showed signs of deterioration over time whether or not edaravone was administered, but administration of edaravone reduced intestinal mucosal damage. An increase in survival rate requires improvements in evaluation methods to enable identification of ischaemic areas.

Topics: Animals; Anticoagulants; Antipyrine; Case-Control Studies; Disease Models, Animal; Edaravone; Fibrin; Free Radical Scavengers; Heparin; Intestine, Small; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Rabbits; Random Allocation; Reperfusion Injury; Thromboembolism; Urokinase-Type Plasminogen Activator

The significance and frequency of fibrin thrombi (FT), the pathological hallmark of disseminated intravascular coagulation (DIC), in ischemic intestine were analyzed in a retrospective study of the infarcted bowel of patients with occlusive mesenteric ischemia (OMI) and nonocclusive mesenteric ischemia (NOMI). Representative intestinal sections were studied from 10 patients with NOMI of the small and/or large bowel and 12 patients, with OMI of varied etiology. Three patients with inflammatory bowel disease and 1 patient with DIC and bowel necrosis were also studied. Routine hematoxylin and eosin stains for fibrin were prepared for each specimen. The number of FT was quantitated. FT were identified in each of the 10 cases of NOMI; however in only 2 were they prominent. FT were identified in 6 of the 12 cases of OMI and in 4 of these 6 they were a prominent feature. Rare FT were present in the cases of inflammatory bowel disease and did not correlate with the inflammatory process. No FT were present in the intestinal sections of the DIC case. FT are a nonspecific feature of necrosis and can be identified in both occlusive and nonocclusive ischemic bowel disease. Their presence in the intestine of NOMI therefore cannot be used to implicate DIC as the primary cause of this entity.

Topics: Blood Platelets; Disseminated Intravascular Coagulation; Enteritis; Fibrin; Humans; Infarction; Intestinal Diseases; Intestines; Ischemia; Mesenteric Vascular Occlusion; Mesentery; Necrosis; Retrospective Studies; Thrombosis