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1 Journal of Physiology and Pharmacology

1 2008

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Pharmacological impact on loop gain properties to prevent irregular breathing

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Kiwull-Schone H. , Teppema L. , Wiemann M. , Kalhoff H. , Kiwull P.

Journal of Physiology and Pharmacology

2008

tom 59

nr 1

Theory predicts respiratory instabilities at elevated system loop gain (G), determined by such factors as ventilatory CO2 sensitivity, set-point PCO2, and metabolic rate. In anesthetized rabbits, the effects on G of carbonic anhydrase (CA) inhibitors and of different sodium/proton exchanger type 3 (NHE3) inhibitors were studied. Acetazolamide significantly reduced G by 42.0 ± 9.3% and methazolamide by 35.0 ± 9.5% (each n = 7, P<0.01). Irrespective of the substance, NHE3 inhibition reduced G by 33.0 ± 7.8% (n = 10, P<0.01) at 35.5 ± 1.6 mmHg PaCO2 (mean ±SE), but not at lower arterial CO2 levels (n=5). Since high baseline PCO2 coincides with elevated brainstem NHE3 mRNA expression, this may also account for a higher risk of sleep apnea (or even occurrence of sudden infant death). Therefore, NHE3 inhibitors may gain similar therapeutic importance in the treatment of irregular breathing as CA inhibitors. Generally, effective treatment should aim at a low system loop gain, by reducing respiratory chemosensitivity, improving blood gases and preventing low metabolic rates.