Sirolimus as primary immunosuppression is associated with improved coronary vasomotor function compared with calcineurin inhibitors in stable cardiac transplant recipients.
OBJECTIVE
The aim of this study was to evaluate coronary vasomotor function in cardiac transplant recipients maintained on sirolimus (SRL)- or cyclosporin (CyA)-based immunosuppression.


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.


CONCLUSIONS
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.
Raichlin
Eugenia
E
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.
Prasad
Abhiram
A
Kremers
Walter K
WK
Edwards
Brooks S
BS
Rihal
Charanjit S
CS
Lerman
Amir
A
Kushwaha
Sudhir S
SS
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D019703:Calcineurin / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020123:Sirolimus / Q000627:therapeutic use*; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D007166:Immunosuppressive Agents; D019703:Calcineurin; D020123:Sirolimus