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CLINICAL STUDY: MYOCARDIAL INFARCTION AND ACUTE CORONARY SYNDROME

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

^* Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

Manuscript received June 12, 2002; revised manuscript received August 7, 2002, accepted August 29, 2002.

^* Reprint requests and correspondence: Dr. Masahiro Mohri, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
mmohri{at}med.kyushu-u.ac.jp

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.

Abbreviations and Acronyms   ACh   acetylcholine   ECG   electrocardiogram/electrocardiographic   ISDN   isosorbide dinitrate

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