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Eur J Cardiothorac Surg 2000;17:319-324
© 2000 Elsevier Science NL
a Department of Cardio-thoracic Surgery, Yorkshire Heart Centre, The General Infirmary, Great Georges Street, Leeds LS1 3EX, UK
b School of Biomedical Sciences, University of Leeds, Leeds, UK
Corresponding author. Tel.: +44-113-292-3436; fax: +44-113-292-6657
e-mail: jrsadaba{at}doctors.org.uk
Objective: The radial artery is becoming popular as a conduit for coronary artery surgery but there is concern about its tendency to vasospasm. Diltiazem is used clinically in an effort to prevent vasospasm but there are suggestions that it is relatively ineffective. The first aim of the study was to test the effectiveness of Ca2+ antagonists against vasospasm evoked by vasoconstrictor agonists. Because a large component of vasospasm was resistant to Ca2+ antagonists, the second aim was to test if a different class of vasodilator, nicorandil, might relax the residual tone. Methods: Isometric tension was recorded in human radial artery segments harvested from patients undergoing myocardial revascularization surgery. Results: Diltiazem at 10 µM, which strongly inhibits L-type voltage-gated Ca2+ channels, induced partial relaxation (mean±SEM, 44.6±3.5%, n=31) of phenylephrine-evoked contraction, but only 14.0±4.1% (n=10) and 12.2±4.2% (n=10) relaxation of U46619- (a thromboxane A2 analogue) or endothelin-1-evoked contraction. Strikingly, nicorandil relaxed agonist-evoked contractions that were resistant to diltiazem or nicardipine. In the absence of a Ca2+ antagonist, nicorandil (30 µM) evoked 74.1±5.6% (n=24), 36.8±9.3% (n=10) and 64.5±7.9% (n=14) relaxation of phenylephrine-, U46619- and endothelin-1-evoked contractions. Conclusions: Nicorandil has a marked relaxant effect on contractions evoked by three different vasoconstrictor agonists, and relaxes vasospasm that is resistant to conventional Ca2+ antagonists. These in vitro data suggest that nicorandil might be a useful drug for the inhibition of radial artery vasospasm in myocardial revascularization surgery.
Key Words: Grafting • Vasospasm • Radial artery • Nicorandil
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