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Abstract While high-frequency electrical stimulation often used to treat various biological diseases, it is generally difficult to understand its dynamical mechanisms of action. In this work, high-frequency electrical stimulation is considered in the context of neurological and cardiological systems. Despite inherent differences between these systems, results from both theory and computational modeling suggest identical dynamical mechanisms responsible for desirable qualitative changes in behavior in response to high-frequency stimuli. Specifically, desynchronization observed in a population of periodically firing neurons and reversible conduction block that occurs in cardiomyocytes both result from bifurcations engendered by stimulation that modifies the stability of unstable fixed points. Using a reduced order phase-amplitude modeling framework, this phenomenon is described in detail from a theoretical perspective. Results are consistent with and provide additional insight for previously published experimental observations. Also, it is found that sinusoidal input is energy-optimal for modifying the stability of weakly unstable fixed points using periodic stimulation.