Real-time measurement of nitric oxide in coronary circulation during ischemia reperfusion and analysis of pathophysiological effects

缺血再灌注时冠脉循环一氧化氮实时测量及病理生理效应分析

• 批准号: 08671553
• 负责人: FUJIWARA Takashi
• 金额: $ 1.34万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671553/
• 关键词: nitric oxide (NO); NO microelectrode; coronary circulation; myocardial ischemia; angiotensin converting enzyme inhibitor; 一酸化窒素

Isolated rat hearts perfused in Langendorff mode were used in this experiment. NO concentration in the coronary perfusate ejected from the pulmonary artery was measured using an NO microelectrode (100 mum ; 1 pA corresponds to about 1.5 nM NO).1. Effect of superoxide scavenger during ischemia reperfusionProduction of superoxide radical (・O_2) is considered to increase during ischemia reperfusion. In order to investigate the effect of superoxide on NO concentration in the coronary circulation during ischemia reperfusion, superoxide dismutase (SOD) or synthesized superoxide scavenger was perfused. We were unable to observe any noticeable effects, i.e., NO scavenged by ・O_2 due to seemingly unstable scavenging activities of both scavengers. Perfusion method is currently being modified to maintain the scavenging activities of those scavengers.2. Effdct of angiotensin converting enzyme inhibitor during hypoperfusionNO concentration in the coronary perfusate decreased with decreasing perfusion pressure (100 cmH<@D22@>D2O to 50 cmH<@D22@>D2O,49(]SY.+-。[)4% vs 100 cmH<@D22@>D2O,p<0.05). Perfusion of angiotensin converting enzyme (ACE) inhibitor, imidaprilat (50 nM), increased both perfusion rate (57(]SY.+-。[)3% vs 100 cmH<@D22@>D2O,p<0.05) and NO concentration (44(]SY.+-。[)9 pA,75(]SY.+-。[)6% vs 100 cmH<@D22@>D2O,p<0.05). These results indicate that NO concentration in the coronary perfusate increased with increasing perfusion rate by increased NO.It is supposed that deactivation of bradykinin (agonist of NO synthase ) by ACE was inhibited by ACE inhibitor, resulting in the increase in NO concentration.

本实验采用Langendorff离体大鼠心脏灌流模型。使用NO微电极（100 μ m; 1 pA对应于约1.5nM NO）测量从肺动脉排出的冠状灌注液中的NO浓度。超氧阴离子清除剂在缺血再灌注过程中的作用缺血再灌注时超氧阴离子自由基（·O_2）的产生增加。为探讨超氧化物歧化酶（SOD）对缺血再灌注时冠状循环中NO浓度的影响，本实验采用超氧化物歧化酶（SOD）或合成的超氧化物清除剂灌流冠状循环。我们无法观察到任何明显的影响，即，·O_2对NO的清除作用似乎不稳定。灌流方法目前正在修改，以保持这些清除剂的清除活性。血管紧张素转换酶抑制剂在低灌注时的作用冠状动脉灌流液中NO浓度随灌注压的降低而降低（100 cm H <@D22 @> D_2 O ~ 50 cm H <@D22@> D_2 O，49（SY. ±-. [)4%相对于100 cmH<@D22@> D2 O，p<0.05）。灌注血管紧张素转换酶（ACE）抑制剂咪达普利拉（50 nM）增加了两种灌注速率（57（± SD））。[)3%相对于100 cmH<@D22@> D2 O，p<0.05）和NO浓度（44（± 0.05）μ g/ml）。[)9 pA，75（±）SY。[)6%相对于100 cmH<@D22@> D2 O，p<0.05）。这些结果表明，在冠状动脉灌注液中的NO浓度随着灌注速率的增加而增加，通过增加NO。据推测，血管紧张素转换酶抑制剂抑制血管紧张素转换酶（一氧化氮合酶的激动剂）的缓激肽的失活，导致NO浓度的增加。

项目成果

Mochizuki S: "Direct measurement of nitric oxide in arterial wall using newly developed nitric oxide microsensor." Biomedical Enginneering-Applications,Basis & Communications. 8(4). 18-23 (1996)

Mochizuki S：“使用新开发的一氧化氮微传感器直接测量动脉壁中的一氧化氮。”

Yoshiaki Fukuhiro, Seiichi Mochizuki, Masami Goto, Takashi Fujiwara, Taiji Murakami, Hiroshi Inada, Hisao Masaki, Ichiro Morita, and Fumihiko Kajiya: "6.Real-Time Measurement of Nitric Oxide in Coronary Outflow During Transient Myocardial Ischemia and Rep

Yoshiaki Fukuhiro、Seiichi Mochizuki、Masami Goto、Takashi Fujiwara、Taiji Murakami、Hiroshi Inada、Hisao Masaki、Ichiro Morita 和 Fumihiko Kajiya：“6. 短暂性心肌缺血和恢复期间冠状动脉流出物中一氧化氮的实时测量

望月 精一: "摘出心・血管におけるNOの動態計測" BME. 35・Suppl.125 (1997)

Seiichi Mochizuki：“离体心脏和血管中 NO 的动态测量”BME 35·Suppl.125 (1997)。

Fukuhiro Y: "Real-time measurement of NO release from coronary circulation after transient ischemia." J Mol Cell Cardiol. 28(11). A330 (1996)

Fukuhiro Y：“实时测量短暂性缺血后冠状动脉循环中 NO 的释放。”

Yoshiaki Fukuhiro, Seiichi Machizuki, et.ul: "Ischemic Heart (Chapter6)" Kluwer Academic Publishers, 624 (1998)

Yoshiaki Fukuhiro、Seiichi Machizuki 等：“缺血性心脏（第 6 章）”Kluwer 学术出版社，624 (1998)