ORGAN PROTECTION AND IMPROVEMENT OF SURVIVAL AFTER HEMORRHAGIC SHOCK BY TREATMENT WITH INHALED NITRIC OXIDE(NO) IN A RAT MODEL

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Soichiro Mimuro 浜松医科大学, 医学部附属病院, 講師 (90464114)
• Co-Investigator(Kenkyū-buntansha): 加藤 孝澄 浜松医科大学, 医学部, 准教授 (80204478)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 出血性ショック / 一酸化窒素 / 予後

Outline of Final Research Achievements

Organ dysfunction following hemorrhagic shock and the vital prognosis have not improved sufficiently over time.Control of NO production by intravenousadministration of NO donors and NOS inhibitors has been attempted, but these are not suitable for clinical application. Inhaled NO is an agent with sufficient clinical safety and experience, but it has not been reported for use in the treatment of hemorrhagic shock. Thus, we investigated whether inhaled NO administration leads to differences in survival and central venous NO2 levels in a rat hemorrhagic shock model. The survival rate was higher in the group with hemorrhagic shock followed by inhaled NO compared with the group without inhaled NO (p=0.033) The survival rate increased in hemorrhagic shock rats that were treated with inhaled NO compared with rats that were not. It was suggested that administration of inhaled NO is effective for the early phase of hemorrhagic shock.

Free Research Field

救急集中治療医学

Academic Significance and Societal Importance of the Research Achievements

出血性ショック後の臓器障害や予後は, まだ十分に改善されていない。出血性ショックにおいてNOは臓器障害の機序に関与していると考えられている。出血後の時期によって以下のようにNOの産生が変化する。早期には, endothelial NOS (eNOS）の活性が低下し, NO産生が低下し，晩期には炎症カスケードの誘導により, inducible NOS (iNOS）が過剰に活性化されてNOが過剰に産生される。これが重症化に関与しているとされる。そこにさらに出血性ショックの際にNOを投与することにより予後を改善することにせまった研究といえる