Right ventricular (RV) failure, which is a leading cause of early morbidity and mortality following cardiac transplantation, is attributed to the inability of the donor RV to acutely compensate for the recipient's elevated pulmonary vascular resistance (PVR). Furthermore, the effect of donor brain death (BD) on RV function is unclear. The purpose of this study was to investigate the effects of donor BD on RV function in the setting of elevated PVR. The interactions of the RV and its afterload, the pulmonary vasculature, and left atrial pressure were assessed by measurements of pulmonary vascular energetics and their oscillatory nature using proximal ultrasonic pulmonary artery (PA) flow probe and micromanometers in the proximal and distal PA in 20 mongrel dogs (25.8±0.4 kg, five control animals). A band was placed around the distal PA (PA-systolic gradient >15 mm Hg). BD was induced by rising intracranial pressure and was validated neuropathologically. Data were collected at 0, 2, 4, and 6 h after BD in both banded and control animals. Fourier analysis was used to calculate RV oscillatory power, mean power, and total power (TP). Comparison of changes due to banding were made to baseline measurements using multivariate analysis and paired Student's t test (p<0.05). A significant twofold to fourfold increase in pulmonary impedance and PVR occurred with an acute rise in PA gradient. Control animals tolerated acute increases in PVR without significant changes in TP. There was a significant increase of RV TP from 73 (±11) to 98 (±10) mW at baseline after the acute rise in PVR and impedance. After BD, the response to increased PVR and impedance was abolished significantly compared with baseline and control animals, suggesting a significant loss of compensatory TP to sustain pulmonary vascular blood flow. The data indicate that BD is detrimental to RV mechanical function.