Mechanisms for the inhibition of amiloride-sensitive Na+ absorption by extracellular nucleotides in mouse trachea

Purinergic stimulation of airway epithelial cells induces Cl- secretion and modulates Na+ absorption by an unknown mechanism. To gain insight into this mechanism, we used a perfused micro-Ussing chamber to assess transepithelial voltage (V-te) and amiloride-sensitive short-circuit current (Isc-Amil) in mouse trachea. Exposure to apical ATP or UTP (each 100 mumol/l) caused a large initial increase in lumen negative V-te and I-sc corresponding to a transient Cl- secretion, while basolateral application of ATP/UTP induced only a small secretory response. Luminal, but not basolateral, application of nucleotides was followed by a sustained and reversible inhibition of Isc-Amil that was independent of extracellular Ca2+ or activation of protein kinase C and was not induced by carbachol (100 mumol/l) or the Ca2+ ionophore ionomycin (1 mumol/l). Removal of extracellular Cl- or exposure to 200 muM DIDS reduced UTP-mediated inhibition of Isc-Amil Substantially. The phospholipase inhibitor U73122 (10 mumol/l) and pertussis toxin (PTX 200 ng/ml) both attenuated UTP-induced Cl- secretion and inhibition of Isc-Amil. Taken together, these data imply a contribution of Cl- conductance and PTX-sensitive G proteins to nucleotide-dependent inhibition of the amiloride-sensitive Na+ current in the mouse trachea.

Hemodynamic and ventilatory effects of manual respiratory physiotherapy techniques of chest clapping, vibration, and shaking in an animal model

Chest clapping, vibration, and shaking were studied in 10 physiotherapists who applied these techniques on an anesthetized animal model. Hemodynamic variables (such as heart rate, blood pressure, pulmonary artery pressure, and right atrial pressure) were measured during the application of these techniques to verify claims of adverse events. In addition, expired tidal volume and peak expiratory flow rate were measured to ascertain effects of these techniques. Physiotherapists in this study applied chest clapping at a rate of 6.2 +/- 0.9 Hz, vibration at 10.5 +/- 2.3 Hz, and shaking at 6.2 +/- 2.3 Hz. With the use of these rates, esophageal pressure swings of 8.8 +/- 5.0, 0.7 +/- 0.3, and 1.4 +/- 0.7 mmHg resulted from clapping, vibration, and shaking respectively. Variability in rates and forces generated by these techniques was 80% of variance in shaking force (P = 0.003). Application of these techniques by physiotherapists was found to have no significant effects on hemodynamic and most ventilatory variables in this study. From this study, we conclude that chest clapping, vibration, and shaking 1) can be consistently performed by physiotherapists; 2) are significantly related to physiotherapists' characteristics, particularly clinical experience; and 3) caused no significant hemodynamic effects.