Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery.

Abstract

We have recently demonstrated that fasudil, a Rho-kinase inhibitor, is effective in suppressing coronary artery spasm in patients with vasospastic angina. Thus, blockade of Rho-kinase may provide a novel therapeutic strategy to treat ischemic coronary syndrome caused by the spasm. Severe coronary artery spasm still remains a life-threatening serious complication of coronary artery bypass grafting (CABG). In this study, we examined the inhibitory effect of fasudil in patients with intractable severe coronary spasm after CABG. Three patients who underwent CABG showed severe myocardial ischemia resistant to intensive therapy with intravenous conventional vasodilators, including isosorbide dinitrate (ISDN), diltiazem, and nicorandil. Coronary angiography revealed severe coronary spasm in native coronary arteries and/or bypass arterial grafts in all patients. Since intracoronary and/or intragraft administration of ISDN was ineffective to resolve the spasm, we then administered fasudil (1.5 mg/min for 15 minutes) into the spastic arteries. Fasudil successfully resolved the spasm and improved myocardial ischemia in all patients without any systemic adverse effects. In conclusion, the treatment with fasudil may be useful to treat intractable and otherwise fatal coronary spasm resistant to intensive conventional vasodilator therapy after CABG.

• Authors: Kousuke Inokuchi, Akira Ito, Yoshihiro Fukumoto, Tetsuya Matoba, Akira Shiose, Takahiro Nishida, Munetaka Masuda, Shigeki Morita, Hiroaki Shimokawa
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 44 Issue 3 Pg. 275-7 (Sep 2004) ISSN: 0160-2446 [Print] United States
• PMID: 15475822 (Publication Type: Case Reports, Journal Article)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Protein Kinase Inhibitors
• Nicorandil
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Protein Serine-Threonine Kinases
• rho-Associated Kinases
• Diltiazem
• Isosorbide Dinitrate
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (administration & dosage, analogs & derivatives, therapeutic use)
• Aged
• Coronary Artery Bypass (methods)
• Coronary Vasospasm (diagnosis, drug therapy, physiopathology)
• Diltiazem (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance
• Female
• Humans
• Infusions, Intravenous
• Intracellular Signaling Peptides and Proteins
• Isosorbide Dinitrate (pharmacology)
• Male
• Middle Aged
• Nicorandil (pharmacology)
• Pain, Intractable (drug therapy)
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• rho-Associated Kinases