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

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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 μs) showed no reduction in T. Electrical stimulation at pulse rates of 10 or 20 Hz (16.7 V, pulse width 260 μs) 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.

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References

  1. Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. Eur J Pediatr. 2011;170:1097–105. https://doi.org/10.1007/s00431-011-1409-6.

    Article  Google Scholar 

  2. Frey U, Silverman M, Barabási AL, Suki B. Irregularities and power law distributions in the breathing pattern in preterm and term infants. J Appl Physiol (Bethesda, MD). 1985;1998(85):789–97. https://doi.org/10.1152/jappl.1998.85.3.789.

    Google Scholar 

  3. Eichenwald EC. Newborn C on FA. Apnea of prematurity. Pediatrics. 2015. https://doi.org/10.1542/peds.2015-3757.

    Google Scholar 

  4. Martin RJ, Abu-Shaweesh JM, Baird TM. Apnoea of prematurity. Paediatr Respir Rev. 2004;5(Suppl A):S377–82.

    Article  Google Scholar 

  5. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354:2112–21. https://doi.org/10.1056/NEJMoa054065.

    Article  Google Scholar 

  6. Steer P, Flenady V, Shearman A, Charles B, Gray PH, Henderson-Smart D, et al. High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2004;89:F499–503. https://doi.org/10.1136/adc.2002.023432.

    Article  Google Scholar 

  7. Hoecker C, Nelle M, Poeschl J, Beedgen B, Linderkamp O. Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants. Pediatrics. 2002;109:784–7.

    Article  Google Scholar 

  8. Ergenekon E, Dalgiç N, Aksoy E, Koç E, Atalay Y. Caffeine intoxication in a premature neonate. Paediatr Anaesth. 2001;11:737–9.

    Article  Google Scholar 

  9. Anderson BJ, Gunn TR, Holford NH, Johnson R. Caffeine overdose in a premature infant: clinical course and pharmacokinetics. Anaesth Intensive Care. 1999;27:307–11.

    Google Scholar 

  10. Carnielli VP, Verlato G, Benini F, Rossi K, Cavedagni M, Filippone M, et al. Metabolic and respiratory effects of theophylline in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2000;83:F39–43.

    Article  Google Scholar 

  11. Marcus CL, Meltzer LJ, Roberts RS, Traylor J, Dix J, D’ilario J, et al. Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age. Am J Respir Crit Care Med. 2014;190:791–9. https://doi.org/10.1164/rccm.201406-1092OC.

    Article  Google Scholar 

  12. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007;357:1893–902. https://doi.org/10.1056/NEJMoa073679.

    Article  Google Scholar 

  13. Schmidt B, Anderson PJ, Doyle LW, Dewey D, Grunau RE, Asztalos EV, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012;307:275–82. https://doi.org/10.1001/jama.2011.2024.

    Article  Google Scholar 

  14. Nobile S, Carnielli VP. Caffeine for preterm infants: current indications and uncertainties. Acta Bio-Medica Atenei Parm. 2015;86(Suppl 1):32–5.

    Google Scholar 

  15. Poets CF, Khan SR. Former preterm infants, caffeine was good for you, but now beware of snoring! Am J Respir Crit Care Med. 2014;190:720–1. https://doi.org/10.1164/rccm.201409-1588ED.

    Article  Google Scholar 

  16. Bloch-Salisbury E, Indic P, Bednarek F, Paydarfar D. Stabilizing immature breathing patterns of preterm infants using stochastic mechanosensory stimulation. J Appl Physiol (Bethesda, MD). 1985;2009(107):1017–27. https://doi.org/10.1152/japplphysiol.00058.2009.

    Google Scholar 

  17. Pichardo R, Adam JS, Rosow E, Bronzino J, Eisenfeld L. Vibrotactile stimulation system to treat apnea of prematurity. Biomed Instrum Technol. 2003;37:34–40.

    Article  Google Scholar 

  18. Smith VC, Kelty-Stephen D, Qureshi Ahmad M, Mao W, Cakert K, Osborne J, et al. Stochastic resonance effects on apnea, bradycardia, and oxygenation: a randomized controlled trial. Pediatrics. 2015;136:e1561–8. https://doi.org/10.1542/peds.2015-1334.

    Article  Google Scholar 

  19. Camargo VC, Honorato da Silva S, Freitas de Amorim M, Nohama P. Instrumentation for the detection and interruption of apnea episodes for premature newborn. Conf Proc Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Conf. 2014;2014:2127–30. https://doi.org/10.1109/EMBC.2014.6944037.

    Google Scholar 

  20. Lovell JR, Eisenfeld L, Rosow E, Adam J, Bronzino JD. The design, development and application of a virtual instrument system to assess vibrotactile stimulation to interrupt neonatal apnea. Proc. 19th Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 1997;3:1150–3. https://doi.org/10.1109/iembs.1997.756557.

    Google Scholar 

  21. Svenningsen NW, Wittström C, Hellström-Westas L. OSCILLO-oscillating air mattress in neonatal care of very preterm babies. Technol Health Care Off J Eur Soc Eng Med. 1995;3:43–6.

    Google Scholar 

  22. Korner AF, Guilleminault C, den Hoed JV, Baldwin RB. Reduction of sleep apnea and bradycardia in preterm infants on oscillating water beds: a controlled polygraphic study. Pediatrics. 1978;61:528–33.

    Google Scholar 

  23. Williamson JR, Bliss DW, Browne DW, Indic P, Bloch-Salisbury E, Paydarfar D. Using physiological signals to predict apnea in preterm infants. 2011 Conf. Rec. Forty Fifth Asilomar Conf. Signals Syst. Comput. ASILOMAR, 2011, p. 1098–102. https://doi.org/10.1109/acssc.2011.6190183.

  24. Hoppenbrouwers T, Hodgman JE, Harper RM, Hofmann E, Sterman MB, McGinty DJ. Polygraphic studies of normal infants during the first six months of life: III. Incidence of apnea and periodic breathing. Pediatrics. 1977;60:418–25.

    Google Scholar 

  25. Morton SU, Smith VC. Treatment options for apnoea of prematurity. Arch Dis Child Fetal Neonatal Ed. 2016;101:F352–6. https://doi.org/10.1136/archdischild-2015-310228.

    Article  Google Scholar 

  26. Gaugler C, Marlier L, Messer J. Sensory stimulations for the treatment of idiopathic apneas of prematurity. Arch Pediatr Organe Off Soc Francaise Pediatr. 2007;14:485–9. https://doi.org/10.1016/j.arcped.2007.01.013.

    Google Scholar 

  27. Lin Y-W, Cheng C-M, LeDuc PR, Chen C-C. Understanding sensory nerve mechanotransduction through localized elastomeric matrix control. PLoS ONE. 2009;4:e4293. https://doi.org/10.1371/journal.pone.0004293.

    Article  Google Scholar 

  28. Priplata AA, Niemi JB, Harry JD, Lipsitz LA, Collins JJ. Vibrating insoles and balance control in elderly people. Lancet Lond Engl. 2003;362:1123–4. https://doi.org/10.1016/S0140-6736(03)14470-4.

    Article  Google Scholar 

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Acknowledgements

The authors thank Rana Akleh for the mouse cartoon in Fig. 1

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Correspondence to Samer Bou Jawde or Béla Suki.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Bou Jawde, S., Scheuermann, A., Bartolák-Suki, E. et al. The effect of mechanical or electrical stimulation on apnea length in mice. Biomed. Eng. Lett. 8, 329–335 (2018). https://doi.org/10.1007/s13534-018-0076-1

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