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CLINICAL RESEARCH

Coronary Endothelial Vasomotor Function and Vascular Remodeling in Heart Transplant Recipients Randomized for Tacrolimus or Cyclosporine Immunosuppression

Paraskevi Petrakopoulou, MD^_*, Lydia Anthopoulou, MD, Michael Muscholl, MD^_*, Volker Klauss, MD, Wolfgang von Scheidt, MD^¶, Peter Überfuhr, MD, Bruno M. Meiser, MD, Bruno Reichart, MD and Michael Weis, MD^_*,_*

^_* Medizinische Klinik und Poliklinik I
Herzchirurgische Klinik, Klinikum Grosshadern
Mathematisches Institut
Medizinische Poliklinik des Klinikum Innenstadt; Ludwig-Maximilians University of Munich, Munich, Germany
^¶ Zentralklinikum Augsburg, Augsburg, Germany

Manuscript received May 11, 2005; revised manuscript received October 11, 2005, accepted October 31, 2005.

^_* Reprint requests and correspondence: Dr. Michael Weis, Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany (Email: Michael.Weis{at}med.uni-muenchen.de).

OBJECTIVES: This study aimed to compare changes in coronary endothelial function, systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac) immunosuppression.

BACKGROUND: Functional endothelial abnormalities and intimal thickening are sensitive measures of early cardiac allograft vasculopathy (CAV).

METHODS: The randomized, prospective study was performed in two groups of 22 patients, maintained on Tac or CyA and mycophenolate mofetil immunosuppression, 1 and 12 months after heart transplantation. We investigated epicardial luminal diameter, coronary blood flow velocity, and ET-1 plasma levels at 1 and 12 months after transplantation. Structural coronary alterations were determined using intravascular ultrasound.

RESULTS: Epicardial vasomotor function at baseline and during follow-up was comparable between the groups. Deterioration of microvascular endothelial function during follow-up was significantly enhanced in the CyA versus Tac group (p < 0.05). Circulating ET-1 concentration increased in the CyA group but significantly decreased over time in the Tac group (CyA +17% vs. Tac –25%; p < 0.05). The time-dependent increase in mean intimal area was significantly enhanced in the CyA versus Tac group, whereas the vessel area significantly increased during follow-up in the Tac compared with the CyA group.

CONCLUSIONS: Epicardial endothelial function is comparable between CyA- and Tac-treated patients. Microvascular endothelial function deteriorates more in CyA-treated patients, a finding that correlates with enhanced ET-1 concentration and an increased intimal area during follow-up. The mean vessel area in the Tac group increased over time, indicating positive vascular remodeling. Tac is superior to CyA with respect to microvascular endothelial function, intimal thickening, and vascular remodeling.

Abbreviations and Acronyms   AZA = azathioprine   CAV = cardiac allograft vasculopathy   CFR = coronary flow velocity reserve   CyA = cyclosporin A   ET-1 = endothelin-1   Fb = baseline flow velocity   Fp = maximal flow velocity   HLA = human leukocyte antigen   IVUS = intravascular ultrasound   MMF = mycophenolate mofetil   MPA = mycophenolic acid   PGI2 = prostacyclin   Tac = tacrolimus

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