2004 Fiscal Year Final Research Report Summary
Pancreatic protease and activation of leukocyte during MOF
| Project/Area Number |
14571131
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MITSUOKA Hiroshi Hamamatsu University School of Medicine, Second Department of Surgery, Assistant, 医学部附属病院, 助手 (10324360)
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| Co-Investigator(Kenkyū-buntansha) |
UNNO Naoki Hamamatsu University School of Medicine, Second Department of Surgery, Lecturer, 医学部附属病院, 講師 (20291958)
SUZUKI Shohachi Hamamatsu University School of Medicine, Second Department of Surgery, Lecturer, 医学部附属病院, 講師 (20196827)
NAKAMURA Satoshi Hamamatsu University School of Medicine, Second Department of Surgery, Professor, 医学部, 理事 (00090027)
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| Project Period (FY) |
2002 – 2004
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| Keywords | intestinal ischemia / shock / leukocyte / protease / multiple organ failure |
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| Research Abstract |
Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naive donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naive donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.
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