World J. Surg. 23, 36 – 43, 1999 WORLD Journal of SURGERY © 1999 by the Socie ´te ´ Internationale de Chirurgie Inﬂuence of Brain Death and Cardiac Preservation on Systolic and Diastolic Function and Coronary Circulation in the Cross-circulated Canine Heart Ga ´bor Szabo ´, M.D., 1 Christian Sebening, M.D., 1 Thilo Hackert, 1 Lutz Hoffmann, 1 Karin Sonnenberg, 1 Christian Hagl, M.D., 2 Ursula Tochtermann, M.D., 1 Christian F. Vahl, M.D., 1 Siegfried Hagl, M.D. 1 1 Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany 2 Department of Cardiac Surgery, University of Hannover, Konstanty-Gutschow-Strasse 8, 30625 Hannover, Germany Abstract. Previous studies have demonstrated hemodynamic instability and cardiac dysfunction in the brain-dead organ donor. It remains unclear if primary cardiac dysfunction is responsible for hemodynamic deterioration or decreased cardiac function is secondary to brain death- associated altered loading conditions. Therefore in the present study the effects of brain death on hemodynamics and cardiac function were analyzed in vivo in an open chest model and ex vivo in a cross-circulated heart preparation. In a second protocol, the impact of brain death- associated hemodynamic changes on postischemic graft function was investigated. Brain death was induced injecting saline in a subdural Foley catheter. Induction of brain death led to a hyperdynamic reaction followed by hemodynamic deterioration with a decrease of systemic vascular resistance and myocardial contractility. If the hearts were explanted and assessed ex vivo, no differences were found between control and brain-dead hearts. Furthermore, both control and brain-dead hearts showed full functional recovery after 4 hours of hypothermic ischemic storage. Despite hemodynamic deterioration in situ after brain death, there were no differences between the postischemic function of control and brain-dead hearts. These results indicate that myocardial dysfunction is not irreversible and may be secondary to altered loading conditions, and that the recovery of cardiac function after long-term hypothermic storage is not impaired by the hemodynamic changes observed in situ after brain death induction. These data may also indicate that potential donor hearts might not be excluded from transplantation on the basis of impaired hemodynamic characteristics, especially if they are evaluated by load- dependent parameters. Perioperative donor heart performance is an important issue of cardiac transplantation. About 20% of potential donor hearts must be rejected on the basis of poor primary cardiac function or hemodynamic instability. On the other hand, the major cause of death after transplantation during the early postoperative period is graft failure, mostly in association with pulmonary hypertension [1]. Recent studies suggest that not pulmonary hypertension per se but preexistent myocardial damage [2] as a result of brain death or ischemia-reperfusion injury in association with pulmonary hypertension may cause graft dysfunction [3, 4]. A number of experimental and clinical studies report hemodynamic instability in the donor organism following brain death [3, 5–7], but it remains unclear which mechanisms lead to hemodynamic collapse in brain-dead organ donors. Catecholamine injury and hormone depletion are suggested to play a major role in cardiac dysfunction [3, 5]. In contrast, some studies demonstrated that neurohumoral factors may have only minor importance in brain death-associated cardiac dysfunction [8, 9]. Moreover, there is no evidence in the literature that the heart is the primary target of the detrimental effects of brain death resulting in hemodynamic instability or that myocardial dysfunction is secondary to changed loading condi- tions [6, 10, 11]. It remains also unclear if changes of cardiac function are reversible or irreversible. A further issue of contro- versial discussion is the impact of brain death-associated changes on the ischemic tolerance of the donor hearts and posttransplant graft function. In the present study the effects of brain death on hemodynamics and cardiac function were analyzed in vivo in an open chest model and ex vivo in a cross-circulated heart preparation. The latter was used to exclude any load-dependent effect that may have an inﬂuence on cardiac function. In a second protocol, the impact of brain death-associated hemodynamic changes on postischemic graft function was investigated. Materials and Methods Preparation and Measurements In Vivo Studies. Foxhound dogs (20 –28 kg) were anesthetized with a bolus of pentobarbital (Nembutal; Abott) 12 mg/kg IV, paralyzed with pancuronium bromide (Pancuronium Organon) 0.1 mg/kg as a bolus and then 4 g/kg/min IV, and endotracheally intubated. The level of anesthesia was maintained with piritramid (Dipidolor; Janssen) 1 mg/kg as a bolus and then 15 g/kg/min IV. The dogs were ventilated with a mixture of N 2 O and O 2 (40%/ 60%) at a frequency of 12 to 15/min and a tidal volume starting at 15 ml/kg/min. The settings were adjusted by maintaining arterial partial carbon dioxide pressure levels between 35 and 40 mmHg. The femoral artery and vein were cannulated for recording aortic This International Society of Surgery (ISS)/Socie ´te ´ Internationale de Chirurgie (SIC) article was presented at the 37th World Congress of Surgery International Surgical Week (ISW97), Acapulco, Mexico, August 24 –30, 1997. Correspondence to: G. Szabo ´, M.D.