The Impact of Donor Gender on Cardiac Peri-transplantation Ischemia Injury Mohamad H. Yamani, MD, a Sabri K. Erinc, MD, a Ann McNeill, RN, a Norman B. Ratliff, MD, b Dianna Sendrey, MS, a Lingmei Zhou, MS, c Daniel J. Cook, PhD, d Robert Hobbs, MD, a Gustavo Rincon, MD, a Corinne Bott-Silverman, MD, a James B. Young, MD, a Michael Banbury, MD, e Jose Navia, MD, e Nicholas Smedira, MD, e and Randall C. Starling, MD, MPH a Background: Cardiac allografts from female donors have been shown to be associated with increased risk of transplant vasculopathy. However, the influence of donor gender on peri-transplantation ischemic injury has not been evaluated. Methods: A total of 361 patients (mean age, 52  10 years) underwent cardiac transplantation between January 1998 and December 2002. Patients were divided into 4 groups according to their donor–recipient gender status: Group A, male–male, 156; Group B, male–female, 37; Group C, female–male, 114; and Group D, female–female, 54. Serial right ventricular endomyocardial biopsy specimens were evaluated for ischemic injury during the first 4 weeks after transplantation. Results: Patients were similar in baseline characteristics. An increased incidence of ischemic injury complicated by fibrosis (12.9%, p = 0.03) and subsequent development of transplant vasculopathy (Kaplan-Meier 6-year freedom from vasculopathy, 53.4%; p = 0.012) was noted in Group D. No survival difference was observed among the 4 groups, however. In Group D (F–F), 2 patients underwent retransplantation and 2 patients underwent revascularization. Conclusions: The transplantation of a female cardiac allograft into a female recipient is associated with increased risk of ischemic injury complicated by fibrosis and subsequent transplant vasculopathy. J Heart Lung Transplant 2005;24:1741– 4. Copyright © 2005 by the International Society for Heart and Lung Transplantation. Peri-transplantation ischemia-induced myocardial injury is manifested histologically by myocyte necrosis on serial endomyocardial biopsy specimens. It may be complicated by the development of interstitial fibrosis that has been shown to be associated with advanced allograft coronary vasculopathy and poor long-term outcome. 1 The pathogenesis of ischemic injury has been linked to several factors, such as graft ischemia time, peri- transplantation hemodynamic status of the donor, ino- tropic support required by the donor, myocardial dam- age caused by reperfusion, and the quality of graft preservation during transportation. 2– 4 Ischemia-induced myocardial injury at the time of transplantation influ- ences the development of accelerated allograft athero- sclerosis through a number of mechanisms, including endothelial cell injury and promotion of cellular and vascular rejection. 5 Coronary angiography and intravascular ultrasound studies have indicated that female allografts are at increased risk for the development of transplant vascu- lopathy. 6,7 However, to our knowledge, the impact of donor gender on peri-transplantation ischemic injury has not been evaluated. This study assessed the influ- ence of donor gender on peri-transplantation ischemic injury and fibrosis. METHODS Patient Population Between January 1998 and December 2002, 361 pa- tients (mean age, 52  10 years) underwent heart transplantation at the Cleveland Clinic Foundation. During the first 4 weeks after transplantation, right ventricular endomyocardial biopsy specimens were evaluated for ischemic injury and the subsequent devel- opment of myocardial interstitial fibrosis. Patients were divided into 4 groups according to their donor–recipient gender status: Group A, male– male, 156; Group B, male–female, 37; Group C, female– male, 114; and Group D, female–female, 54. Informa- From the Departments of a Cardiovascular Medicine, b Anatomic Pa- thology, c Biostatistics, d the Allogen Laboratory, and e Cardiothoracic Surgery, Cleveland Clinic Foundation, Kaufman Center for Heart Failure, Cleveland, Ohio. Received November 5, 2004; revised November 15, 2004; accepted February 21, 2005. Reprint requests: Mohamad H Yamani, MD, Cleveland Clinic Founda- tion, Cardiology, F25, 9500 Euclid Avenue, Cleveland, OH 44195. Telephone: 216-444-2755, Fax: 216-444-3407. E-mail: yamanim@ccf.org Copyright © 2005 by the International Society for Heart and Lung Transplantation. 1053-2498/05/$–see front matter. doi:10.1016/ j.healun.2005.02.022 1741