The effect of mechanical or electrical stimulation on apnea length in mice

Abstract

Premature birth is a leading cause of infant mortality which is often attributed to irregular breathing and apnea of prematurity. A common treatment for apnea is caffeine to stimulate the brain's respiratory center. However, caffeine's long term effect on infant development is not fully comprehended. We hypothesized that noninvasive localized body stimulation regularizes breathing pattern. We investigated the impact of electrical or mechanical stimulation on breathing in mice. After the mice were ventilated for 28 s to induce apnea, mice were taken off the ventilator while receiving mechanical, electrical, or no stimulation in a randomized order. Both stimuli targeted the diaphragm area through a custom-built belt with vibrating motors or adhesive electrodes. After each apnea cycle, the time to take the first breath (T) was recorded. The electrical stimulation given at 4.5, 8.3, 16.7 V (pulse rate = 3 Hz, pulse width = 120 ls) showed no reduction in T. Electrical stimulation at pulse rates of 10 or 20 Hz (16.7 V, pulse width 260 ls) showed a detrimental effect increasing T by * 7% compared to control values (p = 0.005, p = 0.038 respectively). High and medium intensity mechanical stimulations significantly reduced T by 11.74 (p \ 10-13) and by 17.08% (p \ 10-8), respectively. Further reducing the amplitude of vibrations did not affect T. When the probe was attached to the ankles, only the high intensity vibrations resulted in a decrease in T (p \ 10-13). Mechanical vibrations, applied at various intensities and locations, could be used to treat irregular breathing and apnea in infants.

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

“…This study has multiple implications. First, we verified the findings of our previous experiment showing that local mechanical stimulation can help alleviate symptoms of apnea and reduce apnea length in an intensity-dependent manner [ 19 ]. We were able to show the consistency with which mechanical stimulation can reduce apnea across multiple species.…”

“…Finally, all stimulations were applied onto the rodent’s abdomen, which differs from the location of applied stimulus on an infant that would be on the ankle or wrist. Our previous study found no significant difference in a rodent’s response to stimulation between the limb and the abdomen; therefore, we believe that our choice of stimulation placement does not significantly impact the results [ 19 ].…”

“…The experimental design closely followed the one described previously [ 19 ]. Briefly, mice (weight = 31.2 ± 3.9 g, Charles River) and rats (rats: weight = 219 ± 33 g, Charles River) were anesthetized intraperitoneally (mice: 0.1 ml/20 g Ketamine-Xylazine cocktail, Ketamine 87.5 mg/kg, Xylazine 12.5 mg/kg; rats:0.4 ml/100 g Ketamine-Xylazine cocktail, Ketamine 100 mg/kg Xylazine 20 mg/kg) and kept under mild anesthesia with additional doses of 0.05 ml/20 g Ketamine for mice and 0.25 ml/100 g of rat-cocktail as needed.…”

“…In order to combine results from multiple experiments, the data from each experiment was normalized to the median of its control. Median normalization was used due to the skewness of the distribution, which also maintained consistency with our previous study [ 19 ]. The combined normalized data from every experimental setting was then tested for normality, and compared between the stimulation types using the non-parametric Friedman test followed by Bonferroni pairwise comparison.…”

“…There may be other phenomena, unrelated to the stochastic nature of the vibrations, that can explain the effects of mechanical stimulations. Additionally, in a recent study, our laboratory showed that it is possible to reduce apnea in mice through the use of deterministic and local vibrations [ 19 ]. Previous studies have not fully investigated deterministic signals, so we aim to complement their findings.…”