Loop Gain of Respiratory Control upon Reduced Activity of Carbonic Anhydrase or Na+/H+ Exchange
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.
KeywordsObstructive Sleep Apnea Sleep Apnea Carbonic Anhydrase Central Sleep Apnea Carbonic Anhydrase Activity
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- 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
- 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
- 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