Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model

Takeshi Adachi, Shingo Hori, Koji Miyazaki, Masahiro Nakagawa, Soshin Inoue, Yozo Ohnishi, Hiroe Nakazawa, Naoki Aikawa, Satoshi Ogawa

研究成果: Article査読

7 被引用数 (Scopus)


In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190°C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n = 7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.

出版ステータスPublished - 1998 3月

ASJC Scopus subject areas

  • 救急医学
  • 集中医療医学


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