Pulmonary Vascular Congestion Selectively Potentiates Airway Responsiveness in Piglets

Abstract

The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals. Congestion alone resulted in small increased in baseline airway (Raw) (14.6 +/- 3.7%) and tissue (Rti) resistance (8. 1 +/- 6.5%). Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/- 29.5%, respectively. The increase in Raw with MCh in the presence of vascular engorgement was significantly greater (67.8 +/- 18.9%) but the increase in Rti (38.1 +/- 13.2%) was similar to that seen in the control group. Morphometric measurements were performed on transverse sections of large and small airways from nine additional piglets (three congested only, three MCh only, and three congestion plus MCh). The thickness of the inner airway wall was similar in all groups. Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets. Compared with MCh only and engorgement only, the amount of airway smooth muscle shortening was greater (p < 0.05) in all airway size groups in piglets that underwent engorgement plus MCh challenge. The results of this study demonstrate that pulmonary vascular engorgement, induced by increased left atrial pressure, selectively enhances the airway, but not the parenchymal, response to inhaled MCh. These changes are associated with increased thickness of the outer airway wall in response to vascular congestion, suggesting that uncoupling of the mechanical interdependence between the airway smooth muscle and the lung parenchyma may have occurred. Mechanical uncoupling may reduce the load opposing smooth muscle shortening resulting in increased airway narrowing in response to low doses of inhaled methacholine.

Impact of microvascular circulation on peripheral lung stability

“…This qualitative observation was confirmed by Hogg et al (14), who demonstrated a tendency to a positive correlation between blood flow and lung expansion. Subsequent studies involving lung function measurements have provided further evidence that pulmonary vascular congestion leads to an increase in lung size and/or stiffness at low lung volume by overstretching the capillary network in the alveolar wall (10,29,36,37). It seems plausible to adapt this mechanism to explain the marked differences in the parenchymal parameters between the perfused and unperfused lungs at low lung volumes on the basis of the stabilizing role of the filled pulmonary capillaries in the maintenance of the physiological alveolar architecture.…”

“…forced oscillations; alveolar wall; elastin; end-expiratory lung volume THE MECHANICAL PROPERTIES of the lungs are significantly influenced by changes in the pulmonary hemodynamic conditions (3,7,9,11,20,21, 27,29,(35)(36)(37)40). Numerous clinical (3,7,9,11,20, 27) and experimental studies (29,36,37) have demonstrated that elevation of the pulmonary blood flow (7,20, 27) and/or pressure (3, 11, 29, 36, 37) leads to a deterioration of the lung function via a decrease in functional residual capacity (FRC) (7) and/or stiffening of the alveolar wall (40). Although the qualitative examinations performed by von Basch (38a) in 1889 suggested that not only congestion, but also pulmonary hypoperfusion, can alter the lung configuration, few data are available concerning the changes in the mechanical conditions of the lungs during hypoperfusion or the complete absence of pulmonary perfusion (21,25,29,35).…”

Clinical relevance of airway remodelling in airway diseases

“…However, this effect is likely to be small given the extent of the changes observed and the absence of large vessels between the ASM and airway lumen [76]. Secondly, dilatation of vessels or rapid movement of fluid from vessels into peribronchial tissues may dissociate the elastic load of the lung parenchyma from contracting smooth muscle [81]. Thirdly, exudation of fluid may also contribute to increased thickness of the inner airway wall.…”

Interactions between pulmonary hemodynamics and lung mechanics

“…The complete returns in the mechanical parameters following serotonin challenges independent from the presence or absence of coronary ischemia implies that the changes we measured resulted from the chronic lung congestion, rather than the acute effects of serotonin. pressures have no consistent consequences on the central airway resistance [56,57], where the edema affects primarily the pulmonary vasculature and is not severe enough to be manifested in the appearance of extravascular edema fluid around the bronchial wall [54]. Reports of impairments in the lung mechanical parameters mentioned the presence of severe interstitial and peribronchial edema [58,59] which was not the case in the present study.…”

“…12) and the severity of BHR. Although mucosal swelling, peribronchial edema and airway smooth muscle hypertrophy have also been proposed as mechanisms contributing to BHR during pulmonary hypertension [3,26,27,54,62], we were unable to detect any of these structural changes in the bronchial wall after left heart failure while BHR was still present. This finding suggests that uncoupling of the airways from the lung parenchyma [29] was not involved either.…”