TO ELUCIDATE THE MECHANISM OF REMOTE ORGAN DYSFUNCTION AFTER INTESTINAL ISCHEMIA-REPERFUSION

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: KOIKE Kaoru Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10267164)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Tetsuyuki Ochanomizu University, Science, Associate Professor, 理学部, 助教授 (50178323) ; AIBOSHI Junichi Nippon Medical School, Medicine, Research Associate, 医学部, 助手 (50256913) ; SHINOZAWA Yotaro Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30129465)
• Project Period (FY): 2002 – 2004
• Keywords: intestine / ischemia / reperfusion injury / brain injury / hemorrhagic shock / Magnetic Resonance Spectroscopy / metabolism / Magnetic Resonance Imaging

Research Abstract

1.Magnetic resonance spectroscopy (MRS) technique provides useful information for the understanding of tissue metabolic changes. We used this technique to investigate the effect of gut ischemia-reperfusion (IR) on the brain. [In vivo 31P MRS] All rats survived more than seven days after gut IR (45min of superior mesenteric artery occlusion). The IR group showed a significant elevation of both phosphomonoesters (PME) and phosphodiesters (PDE) signals on day 2. The PME signal represents phosphocholine, phosphoethanolamine, etc., and the PDE signal indicate membrane degeneration. Compared to normal control animals, lower pH values were observed in both groups. Operation and repeated anesthesia may have produced acidic metabolites such as lactate. [In vitro 1H MRS] The IR group indicated significantly higer levels of N-acetylaspartate, creatines, myo-inositol, lactate and alanine than the sham group on the day 5. These data suggest gut IR provokes metabolic changes in the brain.
2.Biologica l activities of mesenteric lymph after hemorrhagic shock on neutrophils : Previous studies have demonstrated that the ligation of mesenteric lymph duct prevents hernorrhagic shock-induced lung injury. We hypothesized that mesenteric lymph following hemorrhagic shock activates neutrophils (PMNs). Rats were exposed to hemorrhagic shock (40mmHg, 30min) and resuscitated over 2 hours with shed blood + normal saline (shed blood x 2) (HSgroup). Asham group underwent identical procedures without hemorrhage and resuscitation. We collected mesenteric lymph between 1 and 2 hours during the resuscitation phase. Superoxide anion production was measured with the superoxide dismutase inhibitable cytochrome C reduction method. PMS adhesion was measured by the radioactivity of adherent PMNs labeled with 51Cr to fibrinogen, and CD11b surface expression was determined by flow cytometry. Mesenteric lymph in the HS group significantly increased superoxide production, PMN adherence and CDT lb surface expression compared to the sham group. Mesenteric lymph may play a crucial role in the pathogenesis of multiple organ dysfunction syndrome.