Although the artificial cardiac pacemaker has contributed to the management of patients with serious arrhythmias, its rate-responsive function is not sufficient to provide physiological regulation of heart rate (HR). To achieve truly physiological rate response in any given patient, we propose a framework to develop a pacemaker directly regulated by sympathetic nerve activity (SNA). In eight anesthetized rabbits, we quantified the dynamic transduction characteristics from SNA to HR as a transfer function. We then characterized the decoding rule as an impulse response, that is the transfer characteristics in the time domain. The transfer function was approximated by a first-order, low-pass filter with lag time (corner frequency: 0.024 +/- 0.013 Hz, lag time: 0.98 +/- 0.09 s). Predicted HR correlated well with measured HR (r = 0.80-0.98). The standard error of the prediction relative to mean HR was only 1.2 +/- 0.7%, indicating that the prediction was reasonably accurate. Direct decoding of SNA to predict instantaneous HR is possible through this analysis. This framework should enable development of a neurally regulated artificial pacemaker.