Search

Lung resistance ( R L ) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in R L , but the mechanism is not entirely clear. The first step toward understanding the effect of DI is to determine how each of the resistance components is affected by DI. In the present study, we measured R L and apparent airway resistance ( R AW , which combines the effects of airway resistance and airway heterogeneity) simultaneously before and after a DI in acetylcholine (ACh)-challenged ex vivo sheep lungs. We found that at normal breathing frequency (0.25 Hz) ACh-challenge led to a doubling of R L , 80.3% of that increase was caused by an increase in R AW ; the increase in apparent tissue resistance ( R T ) was insignificant. 57.7% of the increase in R AW was abolished by a single DI. After subtracting R AW from R L , the remaining R T was mostly independent of ACh-challenge and its reduction after a DI came mostly from the change in the mechanical properties of lung parenchyma. We conclude that at normal breathing frequency, R L in an unchallenged lung is mostly composed of R T , and the increase in R L due to ACh-challenge stems mostly from the increase in R AW and that both R AW and R T can be greatly reduced by a DI, likely due to a reduction in true airway resistance and heterogeneity, as well as parenchymal tissue hysteresis post DI.

Lung resistance ( R L ) and elastance ( E L ) can be measured during positive or negative pressure ventilation. Whether the different modes of ventilation produce different R L and E L is still being debated. Although negative pressure ventilation (NPV) is more physiological, positive pressure ventilation (PPV) is more commonly used for treating respiratory failure. In the present study, we measured lung volume, airway diameter, and airway volume, as well as R L and E L with PPV and NPV in explanted sheep lungs. We found that lung volume under a static pressure, either positive or negative, was not different. However, R L and E L were significantly higher in NPV at high inflation pressures. Interestingly, diameters of smaller airways (diameters <3.5 mm) and total airway volume were significantly greater at high negative inflation pressures compared with those at high positive inflation pressures. This suggests that NPV is more effective in distending the peripheral airways, likely due to the fact that negative pressure is applied through the pleural membrane and reaches the central airways via the peripheral airways, whereas positive pressure is applied in the opposite direction. More distension of lung periphery could explain why R L is higher in NPV (vs. PPV), because the peripheral parenchyma is a major source of tissue resistance, which is a part of the R L that increases with pressure. This explanation is consistent with the finding that during high frequency ventilation (>1 Hz, where R L reflects airway resistance more than tissue resistance), the difference in R L between NPV and PPV disappeared.

Deep inspiration (DI)-induced bronchodilation is the first line of defense against bronchoconstriction in healthy subjects. A hallmark of asthma is the lack of this beneficial effect of DI. The mechanism underlying the bronchodilatory effect of DI is not clear. Understanding the mechanism will help us unravel the mystery of asthma pathophysiology. It has been postulated that straining airway smooth muscle (ASM) during a DI could lead to bronchodilation and bronchoprotection. The hypothesis is currently under debate, and a central question is whether ASM is sufficiently stretched during a DI for its contractility to be compromised. Besides bronchoconstriction, another contributor to lung resistance is airway heterogeneity. The present study examines changes in airway diameter and heterogeneity at different lung volumes. Freshly explanted sheep lungs were used in plethysmographic measurements of lung resistance and elastance at different lung volumes, whereas the airway dimensions were measured by computed tomography (CT). The change in airway diameter informed by CT measurements was applied to isolated airway ring preparations to determine the strain-induced loss of ASM contractility. We found that changing the transpulmonary pressure from 5 to 30 cmH 2 O led to a 51% increase in lung volume, accompanied by a 46% increase in the airway diameter with no change in airway heterogeneity. When comparable airway strains measured in the whole lung were applied to isolated airway rings in either relaxed or contracted state, a significant loss of ASM contractility was observed, suggesting that DI-induced bronchodilation and bronchoprotection can result from strain-induced loss of ASM contractility.