Changes in hemodynamic and metabolic parameters (systemic oxygen delivery, [ḊO2], oxygen consumption [O2], arterial lactate content) in brain-dead and control pigs in the absence of any inotropic or fluid support were studied. Brain death was induced by the inflation of a Foley catheter balloon placed into the subdural space of the animals. Serial atrial natriuretic peptide (ANP) determinations were performed to evaluate concomitant changes occurring in the endocrine function of the heart. Experiments were completed by a volume expansion protocol to provide a dynamic evaluation of these parameters. A significant increase in heart rate (from 113±5 to 176±11 beats/ min), pulmonary capillary wedge pressure (from 7±1 to 12±3 mmHg), dP/dt (from 2040±340 to 4200±660 mmHg/sec−1), cardiac output (from 2.4±0.2 to 3.3±0.4 L/min), mean arterial pressure (from 66±8 to 93±14 mmHg), and systemic oxygen delivery (from 360±30 to 530±90 ml/min−1), was observed following brain death induction. These parameters returned below basal values within 60 min. On the contrary, serum lactate and O2 remained unchanged. Following volume expansion, brain-dead pigs exhibited impaired hemodynamic response, with a significant decrease in dP/dt, MAP, and ḊO2. These changes were accompanied by a significant decrease in O2 and a significant increase in lactate plasma levels. At the same time, a similar increase in ANP release was observed in both groups in response to volume expansion, suggesting that despite impaired myocardial contractility, endocrine function of the heart was preserved following brain death. We conclude that brain death leads to early impaired left ventricular contractility, which could be responsible for the changes observed in aerobic to anaerobic metabolism in response to rapid volume infusion. These results suggest that the use of fluid infusion to reduce the need in inotropic support in conventional therapeutic modalities should be used with care in the management of a brain-dead potential organ donor.