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

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 (S_L ) [Honda et al., 1983; Khoo, 2000] at the intersection of both curves, by which also the arterial set point PCO₂ (PspCO₂) is determined.