1996 Fiscal Year Final Research Report Summary
Effect of inhaled nitric oxide on the pulmonary lung injury
| Project/Area Number |
07671661
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Tottori University |
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Principal Investigator |
ISHIBE Yuichi Tottori University Faculty of Medicine Dept.of Anesthesiology and Reanimatology, 医学部, 助教授 (40122014)
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| Project Period (FY) |
1995 – 1996
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| Keywords | acute lung injury / ischemia reperfusion lung injury / nitric oxide / lipopolisaccharide / thrombnoxane B_4 receptor inhibitor / chemiluninescence |
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| Research Abstract |
Acute lung injury (ALI) is known to develop with an initiation of the activated white blood cells (WBC) by release of cytokines, as a result of acute inflammatory response. Precise mechanisms and effective treatment, however, do not elucidated. We designed the study to be clear the pathophysiology of an ischemia reperfusion (IR) lung injury and to investigate the effect of the inhaled nitric oxide (NO) to the IR lung injury. The ventilation and perfusion of the extirpated rabbit lungs were interrupted for 60 minutes and reperfused with ventilation, then pulmonary capillary permeability coefficient (Kfc), pulmonary vascular resistance (PVR) were measured at every 30 minutes. At the end of the study, the wet to dry lung weight ratio (W/D), WBC,myeloperoxidase (MPO) activity, nitric oxide products (NOx), cyclic GMP (cGMP) from the bronchoalveolar lavage fluid (BALF) were analyzed and the degree of damage of the pulmonary vasculature were evaluated. PVR and Kfc were immediately increased a
… More
fter reperfusion, and it returned to normal level at 30 minutes, but exaggerated again at 60 minutes. W/D increased and NOx and cGMP decreased. Inhalation of NO during reperfusion phase inhibited these dysfunction the pulmonary vasculature and consequently inhibited the increase of lung water. These results suggest that IR lung injury may be induced after 60 minutes ischemia partially due to the inhibition of NO-cGMP pathway, and therefore exogenous NO inhalation may be beneficial to these abnormality.
In the second study, effect of leukotrien B_4 (LTB_4) on the acute lung injury induced with lipopolysaccharide (LPS) was investigated in the rabbit. LPS decreased WBC in the cirlutated blood at 30 minutes after LPS injection and increased MPO activities in the BALF and W/D ratio at 6hr after LPS treatment. Simultaneously CL of the blood increased regardless of the activation with zymozan, and complement activities decreased. These findings strongly suggest that LPS activates WBC and induced ALI.Pretreatment with LTB_4 receptor antagonist inhibited the increase in W/D ratio. Furthermore CL level with zymozan stimulation increased but CL without zymozan stimulation did not. These results suggest that LTB_4 receptor antagonist could not inhibit the threshold of stimulation of activated WBC,but inhibit the production of free redical oxygen species unless the second attack occur, and consequently play a significant role of inhibition to develop of pulmonary vascular injury. Less
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