Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm

Masahiro Mohri, Hiroaki Shimokawa, Yoji Hirakawa, Akihiro Masumoto, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

158 Citations (Scopus)

Abstract

OBJECTIVES: We sought to determine whether a potent Rho-kinase inhibitor fasudil prevents the occurrence of myocardial ischemia in patients with microvascular angina attributable to coronary microvascular spasm. BACKGROUND: Effective treatment of patients with angina who have normal coronary arteriograms (microvascular angina) has not yet been established. Rho-kinase-mediated calcium sensitization of the myosin light chain in smooth muscle cells has been implicated as substantially contributing to vascular hyperconstriction. METHODS: We studied consecutive 18 patients with angina and normal epicardial coronaries in whom intracoronary acetylcholine (ACh) induced myocardial ischemia (ischemic electrocardiographic changes, myocardial lactate production, or both) without angiographically demonstrable epicardial coronary vasospasm. All patients underwent a second ACh challenge test after pretreatment with either saline (n = 5) or fasudil (4.5 mg intracoronarily, n = 13). RESULTS: Myocardial ischemia was reproducibly induced by ACh in the saline group. In contrast, 11 of the 13 patients pretreated with fasudil had no evidence of myocardial ischemia during the second infusion of ACh (p < 0.01). The lactate extraction ratio (median value [interquartile range]) during ACh infusion was improved by fasudil pretreatment, from -0.16 (-0.25 to 0.04) to 0.09 (0.05 to 0.18) (p = 0.0125). CONCLUSIONS: Fasudil ameliorated myocardial ischemia in patients who were most likely having coronary, microvascular spasm. The inhibition of Rho-kinase may be a novel therapeutic strategy for this group of patients with microvascular angina.

Original languageEnglish
Pages (from-to)15-19
Number of pages5
JournalJournal of the American College of Cardiology
Volume41
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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