European Heart Journal Advance Access originally published online on April 21, 2009
European Heart Journal 2009 30(11):1356-1363; doi:10.1093/eurheartj/ehp123
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Sirolimus as primary immunosuppression is associated with improved coronary vasomotor function compared with calcineurin inhibitors in stable cardiac transplant recipients
1 William J. von Liebig Transplant Center and the Division of Cardiovascular Diseases, Mayo Clinic (Go 5-469), 200 First Street, SW, Rochester, MN 55905, USA
2 Center for Coronary Physiology and Imaging, Mayo Clinic, Rochester, MN 55905, USA
3 Department of Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
Received 12 October 2008; revised 5 February 2009; accepted 10 March 2009; online publish-ahead-of-print 21 April 2009.
* Corresponding author. Tel: +1 507 284 0294, Fax: +1 507 266 0228, Email: kushwaha.sudhir{at}mayo.edu
Aims: The aim of this study was to evaluate coronary vasomotor function in cardiac transplant recipients maintained on sirolimus (SRL)- or cyclosporin (CyA)-based immunosuppression.
Methods and results: Endothelium-independent response to intracoronary nitroglycerin and adenosine and endothelium-dependent response to intracoronary acetylcholine (Ach) were assessed in 15 SRL- and 21 CyA- treated subjects with angiographically normal coronary arteries. Baseline mean blood pressure was lower in the SRL group (85.6 ± 10.3 vs. 105.2 ± 8.7 mmHg, P = 0.002). There was no difference between the groups in coronary flow reserve after adenosine administration in multivariable analysis (P = 0.34). Nitroglycerin administration resulted in increase in coronary artery diameter in the SRL compared with the CyA groups (2.79 ± 0.54 vs. 2.57 ± 0.61, P = 0.0036). In 13 SRL-treated subjects without evidence of cardiac allograft vasculopathy (CAV), Ach administration resulted in less epicardial vasoconstriction compared with CyA-treated subjects (2.7 ± 17.7 vs. –15.6 ± 17.2%, P = 0.005). Two SRL-treated subjects with three-dimensional intravascular ultrasound evidence of CAV developed coronary spasm in response to Ach 10–4. Microvascular endothelial function did not differ between the groups.
Conclusion: Sirolimus immunosuppression is associated with less pronounced coronary epicardial endothelial dysfunction compared with CyA immunosuppression. Improvement of coronary vasomotor function with SRL may be an important mechanism for the prevention of CAV.
Key Words: Atherosclerosis • Blood flow • Endothelium • Transplantation • Sirolimus