Advertisement

Loop Gain of Respiratory Control upon Reduced Activity of Carbonic Anhydrase or Na+/H+ Exchange

  • HEIDRUN KIWULL-SCHÖNE
  • LUC TEPPEMA
  • MARTIN WIEMANN
  • PETER KIWULL
Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 580)

Abstract

Considerations from control theory revealed that an elevated gain of the feedback loop may lead to instability of the respiratory system, e.g. during sleep [Longobardo et al.,1982; Honda et al., 1983; Khoo, 2000; Dempsey et al., 2004]. In respiratory medicine, the carbonic anhydrase (CA) inhibitor acetazolamide is known to reduce the incidence of apneas in mountain sickness [Swenson et al., 1991]or sleep disordered breathing [Tojima et al., 1988; Verbraecken et al., 1998]. Other clinical studies revealed that patients prone to sleep apnea showed an increased sodium/proton exchange activity in their lymphocytes [Tepel et al., 2000]. To predict possible protective effects of substances inhibiting either carbonic anhydrase activity or sodium/proton exchange, we evaluated steady state feedback loop characteristics of the respiratory control system from previous studies in anaesthetized rabbits [Kiwull-Schöne et al., 2001a,b]. Steady state loop gain (G) was assessed as ratio of the slope of the CO2 response (S) and that of the metabolic hyperbola (SL ) [Honda et al., 1983; Khoo, 2000] at the intersection of both curves, by which also the arterial set point PCO2 (PspCO2) is determined.

Keywords

Obstructive Sleep Apnea Sleep Apnea Carbonic Anhydrase Central Sleep Apnea Carbonic Anhydrase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Dempsey JA, Smith CA, Przybylowski T, Chenuel B, Xie A, Nakayama H, Skatrud JB. The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep. J Physiol 2004, 560: 1–11.PubMedCrossRefGoogle Scholar
  2. Honda Y, Hayashi F, Yoshida A, Ohyabu Y, Nishibayashi Y, Kimura H. Overall “gain” of the respiratory control system in normoxic humans awake and asleep. J Appl Physiol 1983, 55: 1530–1535.PubMedGoogle Scholar
  3. Khoo MCK. Determinants of ventilatory instability and variability. Respir Physiol 2000, 122: 167–182.PubMedCrossRefGoogle Scholar
  4. Kiwull-Schöne H, Kiwull P. Effectiveness of the peripheral chemoreflex control system in the adjustment of arterial O2 pressure and O2-Hb saturation. Adv Exp Med Biol 1997, 428: 433–438.PubMedGoogle Scholar
  5. Kiwull-Schöne HF, Teppema LJ, Kiwull PJ. Low-dose acetazolamide does affect respiratory muscle function in spontaneously breathing anesthetized rabbits. Am J Resp Crit Care Med 2001a, 163: 478–483.Google Scholar
  6. Kiwull-Schöne H, Wiemann M, Frede S, Bingmann D, Wirth KJ, Heinelt U, Lang H-J, Kiwull P. A novel inhibitor of the Na+/H+ exchanger type 3 activates the central respiratory CO2 response and lowers the apneic threshold. Am J Resp Crit Care Med 2001b, 164: 1303–1311.Google Scholar
  7. Longobardo GS, Gothe B, Goldman MD, Cherniack NS. Sleep apnea considered as a control system instability. Respir Physiol 1982, 50: 311–333.PubMedCrossRefGoogle Scholar
  8. Swenson ER, Leatham KL, Roach RC, Schoene RB, Mills WJ, Hackett PH. Renal carbonic anhydrase inhibition reduces high altitude sleep periodic breathing. Respir Physiol 1991, 86: 333–343.PubMedCrossRefGoogle Scholar
  9. Tepel M, Sanner BM, Van der Giet M, Zidek W. Increased sodium-proton antiporter activity in patients with obstructive sleep apnea. J Sleep Res 2000, 9: 285–291.PubMedCrossRefGoogle Scholar
  10. Tojima H, Kunitomo F, Kimura H, Tatsumi K, Kuriyama T, Honda Y. Effects of acetazolamide in patients with the sleep apnea syndrome. Thorax 1988, 43: 113–119.PubMedCrossRefGoogle Scholar
  11. Verbraecken J, Willemen M, De Cock W, Coen E, Van de Heyning P, De Backer W. Central sleep apnea after interrupting longterm acetazolamide therapy. Respir Physiol 1998, 112: 59–70.PubMedCrossRefGoogle Scholar
  12. Wiemann M, Frede S, Bingmann D, Kiwull P, Kiwull-Schöne H. Sodium/proton exchanger 3 in the medulla oblongata and set point of breathing control. Am J Resp Crit Care Med 2005 (in press)Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • HEIDRUN KIWULL-SCHÖNE
    • 1
  • LUC TEPPEMA
    • 2
  • MARTIN WIEMANN
    • 3
  • PETER KIWULL
    • 1
  1. 1.Dept. of PhysiologyRuhr-UniversityBochumGermany
  2. 2.Dept. of AnesthesiologyLeiden UniversityThe Netherlands
  3. 3.Dept. of PhysiologyUniversity of Duisburg-EssenGermany

Personalised recommendations