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(Circulation. 2002;105:1768.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation

Claudio Ferri, MD; Giuliana Properzi, MD; Gianluca Tomassoni, MD; Anna Santucci, MD; Giovambattista Desideri, MD; Anna Elisa Giuliani, MD; Randall C. Starling, MD, MPH; Norman B. Ratliff, MD; Daniel J. Cook, PhD; Patrick McCarthy, MD; James B. Young, MD; Mohamad H. Yamani, MD

From the University of L’Aquila, Department of Internal Medicine and Public Health (C.F., G.P., G.T., A.S., G.D., A.E.G.), Italy; and Departments of Cardiovascular Medicine (R.C.S., J.B.Y., M.H.Y.), Anatomic Pathology (N.B.R.), and Cardiothoracic Surgery (P.M.), and the Allogen Laboratory (D.J.C.), Cleveland Clinic Foundation, Ohio.

Correspondence to Mohamad H. Yamani, MD, Cleveland Clinic Foundation, Cardiovascular Medicine-F25, 9500 Euclid Ave, Cleveland, OH 44145. E-mail yamanim{at}ccf.org

Background— Endothelin-1 (ET-1), a potent vasoconstrictor, is released in response to several inflammatory cytokines after heart transplantation. The present study correlated patterns of myocardial ET-1 expression in heart biopsies with acute rejection, post-transplantation ischemic injury, and subsequent development of coronary vasculopathy.

Methods and Results— Patterns of myocardial ET-1 expression were evaluated in 47 heart transplant recipients at 3 months after transplant. Transplant vasculopathy was documented by coronary angiography at 2 years after transplant. Expression of ET-1 was tabulated for both blood vessels and the interstitium. Vascular ET-1 expression was positive in 7/17 (41%) of patients with greater than grade 2 (International Society Heart Lung Transplant) rejection compared with 3/30 (10%) of patients with grade 0 and grade 1A rejection (P=0.02). Compared with patients with negative interstitial ET-1 expression (n=22), patients with positive interstitial ET-1 expression (n=25) had higher incidence of post-transplantation ischemic injury (52% versus 9%, P=0.002), lower mean episodes of acute rejection ( grade 2) during the first 3 months of transplant (1.09±0.66 versus 1.86±1.6, P=0.048), and more common vasculopathy at 2 years (50% versus 15%, P=0.02), and they tended to have worse survival (83.2% versus 100%, P=0.058).

Conclusions— Vascular ET-1 expression is likely to be associated with acute rejection. Interstitial ET-1 expression, however, is more likely to be associated with post-transplantation ischemic injury and subsequent development of coronary vasculopathy.

Key Words: endothelin • rejection • transplantation • ischemia • vasculopathy

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