Wyniki wyszukiwania

1

Patterns of intrathoracic gas volume and airway resistance in children with asthma

100%

Kalhoff H., Lara E., Kiwull P., Kiwull-Schone H.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 5

2

Pharmacological impact on loop gain properties to prevent irregular breathing

88%

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

Journal of Physiology and Pharmacology

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2008

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tom 59

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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.

3

The NHE3 inhibitor AVE1599 stimulates phrenic nerve activity in the rat

76%

Wiemann M., Piechatzek L., Gopelt K., Kiwull-Schone H., Kiwull P., Bingmann D.

Journal of Physiology and Pharmacology

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2008

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tom 59

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nr 1

The effect of AVE1599, an inhibitor of the sodium/proton exchanger type 3 (NHE3), on phrenic nerve (PN) activity was investigated using the working heart brainstem preparation (WHBP). Hypercapnia (pH: -0.1) applied for 10 min reversibly increased PN frequency (f) by 66.0 ± 19.5% and decreased burst duration by 23.3 ± 3% (mean ± SE, n = 21). Similarly, AVE1599 (0.3µM) increased f after 10 and 30 min by 75.1 ± 13.2 and 176 ± 36.2% (n = 10), respectively, and reduced duration of PN bursts by 24.9 ± 10.8%. Hypercapnia-induced increases of f were attenuated by AVE1599. An elevated concentration of AVE1599 (0.9µM) had no significant effect on PN. As AVE1599 accumulates in brain tissue and might interfere with the less affine NHE1, we furthermore tested the NHE1-inhibitor HOE642. In fact, HOE642 (0.9µM) diminished f by 88.5 ± 9.2 and 58.6 ± 10.0% after 10 and 30 min (n = 6), respectively, but did not abolish hypercapnic responses. We conclude that AVE1599 augments central respiratory drive in the WHBP via NHE3 but not NHE1 inhibition.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

1 Journal of Physiology and Pharmacology. Supplement

3 Kiwull P.

3 Kiwull-Schone H.

2 Kalhoff H.

2 Wiemann M.

1 Bingmann D.

1 Gopelt K.

1 Lara E.

1 Piechatzek L.

1 Teppema L.

2 2008

1 2007

Patterns of intrathoracic gas volume and airway resistance in children with asthma

Pharmacological impact on loop gain properties to prevent irregular breathing

The NHE3 inhibitor AVE1599 stimulates phrenic nerve activity in the rat