Several investigators have demonstrated that changes in atrial or ventricular pressure and size may modulate changes in electrophysiologic properties. The coupling of mechanical and electrical changes in the heart has been termed mechano-electrical feedback and is believed to play a role in arrhythmias observed with mitral valve disease, congestive heart failure, and left ventricular hypertrophy. To avoid confounding influences of the autonomic nervous system on electrophysiologic measurements, we measured right atrial and ventricular pacing thresholds with temporary epicardial pacing wires, right ventricular monophasic action potential duration at 90% repolarization during right ventricular pacing at 600 and 400 ms, donor heart rate, systolic, diastolic, and mean arterial and central venous pressures in 22 patients after orthotopic heart transplantation. Each variable was measured at baseline, in the resting supine state, and during graded lower body negative pressure of -10, -20, and -30 mm Hg. All levels of lower body negative pressure resulted in a significant decrease in mean right atrial pressure up to 5 +/- 6 mm Hg at maximal lower body negative pressure, and a significant decrease in mean arterial pressure occurred only at -20 and -30 mm Hg. Lower body negative pressure did not result in a significant change in any electrophysiologic variable despite significant changes in right atrial pressure. Thus, in the denervated transplanted human heart, unloading of the right heart results in no or small changes in atrial or ventricular pacing thresholds and ventricular monophasic action potential duration.