Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina.
BACKGROUND
Increased activity of Rho-kinase causes hypercontraction of vascular smooth muscle and has been implicated as playing a pathogenetic role in divergent cardiovascular diseases such as coronary artery spasm. We examined whether an intracoronary infusion of fasudil, a selective Rho-kinase inhibitor, would attenuate coronary vasoconstrictor responses to acetylcholine (ACh) in patients with vasospastic angina.


RESULTS
We studied 20 consecutive patients in whom coronary artery spasm was provoked by intracoronary ACh. The patients underwent a second ACh challenge after pretreatment with intracoronary saline (n=5) or fasudil (n=15; 300 microg/min for 15 minutes). Angina and coronary vasospasm were reproducibly induced by the second testing in patients who received saline. In contrast, fasudil markedly attenuated the coronary constriction induced by ACh (P<0.001) and prevented the occurrence of chest pain and ischemic ECG changes in all treated patients (both P<0.01 versus saline). Fasudil, at the dose used in this study, did not significantly change systemic hemodynamics or baseline coronary blood flow.


CONCLUSIONS
Fasudil was effective in preventing ACh-induced coronary artery spasm and resultant myocardial ischemia in patients with vasospastic angina. We suggest that this Rho-kinase inhibitor may be a novel therapeutic intervention to treat ischemic coronary syndromes caused by coronary artery spasm.
Masumoto
Akihiro
A
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Mohri
Masahiro
M
Shimokawa
Hiroaki
H
Urakami
Lemmy
L
Usui
Makoto
M
Takeshita
Akira
A
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000789:Angina, Unstable / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D014662:Vasoconstrictor Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000109:Acetylcholine; C049347:fasudil