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Mechanical stimulation has been shown to reduce apnea of prematurity (AOP), a major concern in preterm infants. Previous work suggested that the underlying mechanism is stochastic resonance, amplification of a subthreshold signal by stochastic stimulation. We hypothesized that the mechanism behind the reduction of apnea length may not be a solely stochastic phenomenon, and suggest that a purely deterministic, non-random mechanical stimulation could be equally as effective. Mice and rats were anesthetized, tracheostomized, and mechanically ventilated to halt spontaneous breathing. Two miniature motors controlled by a microcontroller were attached around the abdomen. Ventilation was paused, stimulations were applied, and the time to the rodent's first spontaneous breath (T) was measured. Six spectrally different signals were compared to one another and the no-stimulation control in mice. The most successful deterministic stimulation (D) at reducing apnea was then compared to a pseudo-random noise (PRN) signal of comparable amplitude and frequency. CO 2 %, CO 2 stabilization time (T s ), O 2 saturation (SpO 2 %), and T were also measured. D significantly reduced T compared to no stimulation for medium and high amplitudes. PRN also reduced T, without  a difference between D and PRN. Furthermore, both stimulations significantly reduced T s with no significant differences between the respective stimulations. However, there was no effect of D or PRN on SpO 2 %. The lack of differences between D and PRN led to an additional series of experiment comparing the same D to a band-limited white noise (WN) signal in young rats. Both D and WN were shown to significantly reduce T, with D showing statistical superiority in reduction of apnea. We further speculate that both deterministic and stochastic mechanical stimulations induce some form of mechanotransduction which is responsible for their efficacy, and our findings suggest that mechanical stimulation may be effective in treating AOP.

biomedical engineering letters

Stabilizing breathing pattern using local mechanical vibrations: comparison of deterministic and stochastic stimulations in rodent models of apnea of prematurity