Brain Death Effects on Catecholamine Levels and Subsequent Cardiac Damage Assessed in Organ Donors Silvia Pérez López, PhD, a Jesús Otero Hernández, MD, a,b Natalia Vázquez Moreno, PhD, a Dolores Escudero Augusto, MD, a,b Francisco Álvarez Menéndez, PhD, c and Aurora Astudillo González, PhD d Background: Brain death (BD) causes hemodynamic and neuroendocrine alterations including a catecholamine surge, which in turn causes histologic lesions in cardiac muscle such as contraction bands, focal mononuclear cell infiltrates and cardiomyocyte necrosis. These changes are likely to compromise heart function and could therefore also affect the graft response after heart transplantation. This study was designed to examine the catecholamine surge, the catecholamine release pattern and the histologic lesions traditionally described as characteristic of BD in hearts procured from BD donors. Methods: After BD diagnosis, specimens were taken from the left ventricle (n = 50) for histologic examination. Arterial blood samples were collected from 40 of the donors at different time-points (1 hour before BD; on BD diagnosis; and 1, 2, 3 and 4 hours after BD) to determine catecholamine levels by high-performance liquid chromatography (HPLC). Results: The three hormones examined showed above-normal levels (epinephrine 2.36-fold, norepinephrine 8.56-fold, dopamine 54.76-fold). Release patterns included epinephrine and dopamine peaks at the time of BD and a norepinephrine peak 1 hour later. Fifty percent of the BD donors showed contraction bands and 62% displayed cardiomyocyte necrosis, which was associated with focal mononuclear cell infiltrates in 18% of cases. In 40% of donors, colocalized apoptotic and necrotic damage was observed. Conclusions: Differing extents of BD-associated cardiac lesions were observed in the donors, and 50% also showed apoptotic damage. The expected catecholamine peak at the time of BD was only detected for epinephrine and dopamine. Hormone increases were below those described in the literature, except for dopamine. J Heart Lung Transplant 2009;28:815–20. Copyright © 2009 by the International Society for Heart and Lung Transplantation. Brain-dead patients are the main source of organs for transplantation. However, 20% of hearts from human brain-dead donors are discarded after procurement due to poor cardiac function. 1 Since the initial studies in experimental models, 2,3 it has been reported that brain death (BD) leads to changes that compromise cardiac function and this affects the graft response after trans- plantation. 4,5 The changes produced during BD are related to the hemodynamic and neuroendocrine alterations that occur during cerebral herniation. 6 In animal models, BD first causes an intense activation of the sympathetic nervous system known as the autonomic storm, or cardiovascular hyperdynamic state, 7 which increases catecholamine lev- els to about 7 or 8 times normal concentrations. Thereaf- ter, levels normalize and finally fall below standard levels. 8 This catecholamine release pattern is similar to that seen in a clinical situation. 9 There is good evidence that sym- pathetic stimulation and the consequent increase in circu- lating catecholamines are pivotal in the adverse effects of BD produced in heart allografts. 10,11 BD has also been related to histologic changes in heart tissue, namely the appearance of contraction bands, cardiomyocyte necrosis and focal mononuclear cell infiltrates. 2 These lesions have been correlated with the subsequent graft response and could serve as predictors of acute cardiac rejection. 12 Recently, BD has also been reported to induce apoptosis in animals, including the rat 13,14 and rabbit, 15 and in several human tissues, such as kidney 16,17 and heart. 18 Cardiac apopto- sis reduces the contractile mass available, and this has been linked to heart failure. 19 Apoptosis is a cell function necessary for the removal of unwanted cells during normal development or aging. From the a Unidad de Coordinación de Trasplantes y Terapia Celular, b Servicio de Medicina Intensiva, c Servicio de Bioquímica Clínica and d Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, Oviedo, Spain. Submitted November 15, 2008; revised March 6, 2009; accepted April 10, 2009. Reprint requests: Silvia Pérez López, MD, Laboratorio de Trasplante y Terapia Celular, Hospital Universitario Central de Asturias, Edificio Polivalente A, 1 Planta, C/Celestino Villamil s/n, 33006 Oviedo, Spain. Telephone: + 34-985108000 (ext. 39451). Fax: +34-985108778. E-mail: silvia.perez@sespa.princast.es Copyright © 2009 by the International Society for Heart and Lung Transplantation. 1053-2498/09/$–see front matter. doi:10.1016/ j.healun.2009.04.021 815