Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina

Yoshihiro Fukumoto, Masahiro Mohri, Kosuke Inokuchi, Akira Ito, Yoji Hirakawa, Akihiro Masumoto, Yoshitaka Hirooka, Akira Takeshita, Hiroaki Shimokawa

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Abstract

Epicardial coronary stenosis causes myocardial ischemia; however, the role of coronary microvessels is poorly understood in the pathogenesis of effort angina. We have previously demonstrated that Rho-kinase pathway is substantially involved in coronary arterial hyperconstriction in patients with vasospastic angina and those with microvascular angina. In the present study, we tested our hypothesis that Rho-kinase is involved in coronary microvascular constriction in patients with effort angina. Intracoronary administration of fasudil (300 μg/min for 15 min), a specific Rho-kinase inhibitor, significantly increased oxygen saturation in coronary sinus vein from 37 ± 3% to 41 ± 3% (P < 0.05) but not in six age-matched controls (from 42 ± 3% to 43 ± 3%, P = NS). Furthermore, the fasudil treatment significantly ameliorated pacing-induced myocardial ischemia in patients with effort angina (magnitudes of symptom: 1.5 ± 0.6 to 0.6 ± 0.4, P < 0.01; ischemic ST-segment depression, 1.8 ± 0.3 to 1.0 ± 0.2 mm, P < 0.01; percent lactate production, 50 ± 17% to 0.4 ± 7%, P < 0.01) without significant hemodynamic changes. These results provide the first evidence that Rho-kinase is substantially involved in coronary microvascular dysfunction associated with myocardial ischemia in patients with effort angina, suggesting that Rho-kinase can be a novel therapeutic target in ischemic heart disease.

Original languageEnglish
Pages (from-to)117-121
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume49
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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    Fukumoto, Y., Mohri, M., Inokuchi, K., Ito, A., Hirakawa, Y., Masumoto, A., Hirooka, Y., Takeshita, A., & Shimokawa, H. (2007). Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina. Journal of Cardiovascular Pharmacology, 49(3), 117-121. https://doi.org/10.1097/FJC.0b013e31802ef532