1. Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm
- Author
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Mohri, Masahiro, Shimokawa, Hiroaki, Hirakawa, Yoji, Masumoto, Akihiro, and Takeshita, Akira
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PROTEIN kinases , *CORONARY disease , *NITRATES , *MICROCIRCULATION disorders , *CORONARY heart disease prevention , *ACETYLCHOLINE , *ANGINA pectoris , *CARDIOVASCULAR agents , *CLINICAL trials , *COMPARATIVE studies , *CORONARY circulation , *CORONARY vasospasm , *ENZYME inhibitors , *HEART function tests , *RESEARCH methodology , *MEDICAL cooperation , *PHOSPHOTRANSFERASES , *RESEARCH , *SULFONAMIDES , *TRANSFERASES , *EVALUATION research , *VASODILATORS , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *SIGNAL peptides , *INTRA-arterial infusions , *DISEASE complications , *PREVENTION , *THERAPEUTICS ,SULFONAMIDE drugs - Abstract
: ObjectivesWe 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.: BackgroundEffective 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.: MethodsWe 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).: ResultsMyocardial 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).: ConclusionsFasudil 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. [Copyright &y& Elsevier]
- Published
- 2003
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