| Autor: |
Christian Hierholzer, David J. Tweardy, Jörg C. Kalff, Timothy R. Billiar, G. Audolfsson, Anthony J. Bauer |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Transplantation. 68:1244-1254 |
| ISSN: |
0041-1337 |
| DOI: |
10.1097/00007890-199911150-00006 |
| Popis: |
Background. Pathophysiological states that produce intestinal ischemia/reperfusion injury (I/R) initiate an inflammatory cascade and cause ileus. The aims of this study were to investigate the local cellular responses and molecular mechanisms, which contribute to intestinal dysmotility after selective intestinal I/R injury. Methods. ACI rats were subjected to 75 min SMA clamp-induced ischemia followed by reperfusion and were killed at 0 min, 30 min, and 24 hr. Whole mounts of the jejunum were used to immunohistochemically quantify alterations in leukocytes, and circular muscle strips were used to assess organ bath muscle function. Muscularis and mucosa extracts were isolated from the intestine and used for reverse transcription assisted polymerase chain reaction mRNA measurements of granulocyte-colony stimulating factor and interleukin-6, and for determination of nuclear factor kappa B and Stat3 activation. Results. Intestinal I/R injury resulted in the significant recruitment of neutrophils and monocytes into the intestinal muscularis and a functional suppression in jejunal circular muscle contractions. These I/R injury induced cellular responses were preceded by the molecular activation of nuclear factor kappa B, upregulation of granulocyte colony-stimulating factor and interleukin-6 mRNA and phosphorylation of the downstream signaling and transcription factor Stat3. Conclusions. I/R injury evokes a molecular and cellular inflammatory response within the intestinal muscularis that is associated with a subsequent decrease in intestinal motility. The ischemic/reperfused bowel plays an obligatory role in small bowel transplants and also a major role in the sequelae of severe hemorrhagic shock, that is multi-organ failure and systemic inflammatory response syndrome. The study of this pathological state is important because hemorrhagic shock is the primary cause of death in individuals between the ages of 20 and 35 (1, 2). The systemic response to blood loss and hypotension is characterized by the preferred maintenance of centralized blood flow. This is accomplished by a disproportionate constriction of the splanchnic circulation (3). This vascular phenomenon during hemorrhagic shock makes the small intestine particularly susceptible to I/R injury. Fur |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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