Administration of the Rho-kinase inhibitor, fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina.
BACKGROUND
The Rho/Rho-kinase signaling pathway is known to be involved in the pathogenesis of coronary artery spasm. Previous studies reported the efficacy of the Rho-kinase inhibitor, fasudil, in the prevention and relief of coronary spasm. The usefulness of fasudil in combination with conventional vasodilating agents, however, has not been fully examined in patients with vasospastic angina.


RESULTS
A total of 26 patients (mean age, 61+/-11 years) with documented vasospasm in the left anterior descending coronary artery were examined by the acetylcholine stress test. Coronary diameter at the spasm site was measured at baseline and after the administration of vasodilator agents in the following order: intracoronary nitroglycerin (NTG) (300 microg), intravenous fasudil (30 mg, n=15, fasudil group) or saline (n=11, saline group), and again NTG during coronary angiography. The increase in diameter observed following the first NTG administration was found to be similar in the fasudil and saline groups (38.3+/-23.5% and 42.3+/-17.1%, respectively). The additional change in diameter on fasudil treatment (16.9+/-11.2% increase over the diameter after the first NTG administration) was significantly larger than that with saline (-2.8+/-7.6%, P<0.001). The second administration of NTG did not affect the diameter of the spasm site in either group.


CONCLUSIONS
Fasudil further dilated the site of coronary spasm, which had already been treated with NTG in patients with vasospastic angina. These findings support and extend the previous results that showed the feasibility of employing fasudil as a novel therapeutic approach for coronary spasm.
Otsuka
Toshiaki
T
Department of Internal Medicine and Cardiology, Nippon Medical School Tama-Nagayama Hospital, 1-7-1 Nagayama, Tama-City, Tokyo 206-8512, Japan. otsuka@nms.ac.jp
Ibuki
Chikao
C
Suzuki
Takeshi
T
Ishii
Kensuke
K
Yoshida
Hiroshi
H
Kodani
Eitaro
E
Kusama
Yoshiki
Y
Atarashi
Hirotsugu
H
Kishida
Hiroshi
H
Takano
Teruo
T
Mizuno
Kyoichi
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005996:Nitroglycerin; C049347:fasudil