Endotoxin administration improves hypoxia-induced hyponxygenation and inflammation

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12557097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: General surgery
• Research Institution: The University of Tokyo
• Principal Investigator: MIMURA Yoshikazu The University of Tokyo, The University of Tokyo Faculty of Medicine, Associate Professor (10175614)
• Co-Investigator(Kenkyū-buntansha): OGAWA Toshihisa The University of Tokyo, Faculty of Medicine, Lecturer (80224111) ; HIKI Naoki The University of Tokyo, Faculty of Medicine, Research Associate (30313026)
• Project Period (FY): 2000 – 2002
• Keywords: Hypoxia / Endotoxin / Tolerance / Cytokine

Research Abstract

Endotoxin (Et) tolerance is developed after the pretreatment in animals with sublethal dose of Et and is characterized by a reduced inflammatory cytokine response to subsequent Et challenge. The Et administration also attenuates ischemic injury of rat myocardial tissue flowing hypoxia described as a cross-tolerance. The objective of this study was : 1) to determine whether Et evokes cross-tolerance to rat systemic hypoxia as behaviors of cytokine and catecholamines ; 2) to estimate the circulatory and pulmonary performance in rat systemic hypoxia after endotoxin pretreatment. Wistar rats were pretreated with intraperitoneal injection of 10 /μg/kg/body wt of Et. Systemic hypoxia was achieved by continuous inhalation of the gas mixture (9% oxygen + 91% nitrogen) for 4h. Obtained results were as follows : 1) Et pretreatment prevented the drop of mean arterial pressure and the fall of arterial oxygen pressure during hypoxia : 2) Et pretreatment suppressed the hypoxia-induced cytokines hypersecretion ; 3) Et pretreatment suppressed the norepinephrine to the levels of normoxia. In conclusion, Et pretreatment improves the hypoxia-induced 1) inflammatory responses ; 2) reduction of oxygenation ; 3) anaerobic metabolism ; and 4) high activity of norepinephrine.