Airway blood flow and bronchovascular congestion in sheep

106

The bronchial vasculature is the systemic arterial blood supply to the lung. Although small relative to the pulmonary blood flow, the bronchial vasculature serves important functions and is modified in a variety of pulmonary and airway diseases.Congestion of the bronchial vasculature may narrow the airway lumen in inflammatory airway diseases, and formation of new bronchial vessels (angiogenesis) is implicated in the pathology of a variety of chronic inflammatory, infectious and ischaemic pulmonary diseases. The remarkable ability of the bronchial vasculature to remodel has implications for disease pathogenesis.The contributions of the bronchial vasculature to the pathogenesis of pulmonary disease are reviewed in this article. Eur Respir J 1997; 10: 1173-1180. The bronchial circulation is ideally situated to play an important role in lung defence and in the pathogenesis of a number of airway diseases. The bronchial microvasculature provides nutrient blood flow to the airway epithelium and is important for proper functioning of the mucociliary escalator. Bronchial blood flow is responsive to changes in neural and humoral stimuli and plays a role in conditioning of inspired air. The focus of this review is the potential involvement of the bronchial vasculature in contributing to the pathogenesis of a variety of airway diseases. In particular, we have focused on the possibility of airway narrowing as a consequence of bronchial vascular congestion, and the remarkable proliferative capacity of the bronchial vessels in response to a variety of pulmonary diseases. Bronchial vascular congestionHyperaemia of the bronchial vasculature is often included in descriptions of the pathology of asthma. An example of hyperaemia of the bronchial vasculature is shown in figure 1. This photomicrograph shows a crosssection of a human airway from a patient who died of asthma. The apparent increase in the size and number of vessels inside and outside the smooth muscle layer is clearly visible, suggesting that vascular dilation and proliferation (angiogenesis) could be important components of the airway wall remodelling in asthmatic patients. The airway vasculature is of considerable interest in asthma because it can contribute to the excessive airway narrowing, which is characteristic of this disease. A diagram of an airway ( fig. 2) illustrates the two bronchial vascular plexuses: the peribronchial plexus, located in the adventitial space between the muscle and the surrounding lung parenchyma; and the submucosal vascular plexus, located beneath the epithelial layer. Dilation, exudation or transudation from these vessels could contribute to the excessive airway narrowing observed in asthma. Relaxation of the bronchial vascular smooth muscle and/or an increase in the intravascular pressure will lead to congestion of these vessels. This bronchial vascular congestion could result in a reduction in the area of the airway lumen and/or an increase in the outer diameter of the airway. The latter effect could uncouple the airway smoo...

Section: Bronchial Vascular Congestionmentioning

confidence: 70%

Section: Bronchial Vascular Congestionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Bronchial vascular congestion and angiogenesis

Charan

Baile²,

Paré³

1997

106

“…Although the airway vasculature is known to occupy a significant portion of the inner bronchial wall [212,213], with respect to airway blood and vascular engorgement the reports are conflicting [78,[213][214][215]. There is less controversy concerning the effect of airway oedema, which narrows the airways by increasing the thickness of the inner bronchial wall and contributes to airway hyperreactivity to the same degree that airway muscle shortening causes greater luminal narrowing compared with the normal airway [9,216].…”

Section: Airway Conductancementioning

confidence: 99%

Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma

Horváth

Wanner²

2006

Inhaled corticosteroids suppress airway inflammation and components of airway remodelling in bronchial asthma. In the tracheobronchial (airway) vasculature, these include the inhibition of inflammatory hyperperfusion, microvascular hyperpermeability, mucosal oedema formation, and the formation of new blood vessels (angiogenesis).Corticosteroids are now known to exert their effects on the airway vasculature through genomic and nongenomic mechanisms. Genomic actions involve the regulation of target genes, and suppress most of the vascular elements of inflammation and angiogenesis in the airway. In contrast, nongenomic actions are mediated by rapid cellular mechanisms, and induce transient vasoconstriction in the airway, thereby reversing inflammatory hyperperfusion.The vascular actions of corticosteroids contribute to controlling clinical symptoms of asthma primarily by influencing airway calibre in the lung periphery and airway hyperreactivity.In this review article, recent advances into the understanding of cellular mechanisms and the clinical implications of the interaction of inhaled corticosteroids and the airway vasculature in asthma are reviewed.

“…The importance of the vascular hyperresponsiveness is unclear. A study investigating the contribution of vascular volume to airway narrowing in sheep suggested that a 50% increase in vascular volume caused by inhaled histamine had little effect on airway narrowing, at least in large cartilaginous airways [34].…”

Section: Histamine-induced Changes In 99m Tc-dtpa Permeabilitymentioning

confidence: 99%

Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep

Wells¹,

Hanafi²,

Jg³

1996

Epithelial damage greatly increases the flux of a low molecular weight tracer 99m technetium-diethylenetriamine penta-acetic acid ( 99m Tc-DTPA) from tracheal lumen to venous-blood in anaesthetized sheep. We have now investigated whether epithelial damage induced by the detergent, Triton X-100, alters the effects of luminal histamine on blood flow and 99m Tc-DTPA flux.The cervical trachea was filled with Krebs-Henseleit solution containing 99m Tc-DTPA. Tracheal arterial flow was measured and tracheal venous blood collected. The lumen was exposed to 100 µM histamine on two occasions (Hist 1 and Hist 2) for 15 min. In six out of 11 sheep, the lumen was also exposed to 0.2% Triton X-100 between Hist 1 and Hist 2.Triton X-100 increased the baseline 99m Tc-DTPA permeability coefficient from -5.3×10 -7 to -400±130×10 -7 cm·s -1 . After epithelial damage, Hist 2 produced significantly greater changes in arterial and venous flows than Hist 1 (n=5) (0-5 min: Hist 1 Q'a=+6.4±0.8%, Q'v=+6.2±6.2%; Hist 2 Q'a=+36.7±12.2%, Q'v=+35.4±8.8%). Similar changes did not occur in the controls. Venous 99m Tc-DTPA concentration during Hist 2 after epithelial damage (0-5 min -37.7±6.9%) was significantly different from Hist 1 (+5.2±7.0%).Thus, after epithelial damage, luminal histamine produces more rapid and larger changes in blood flow and a greater reduction in venous 99m Tc-DTPA concentration. Eur Respir J., 1996, 9, 78- It has been established by in vitro studies [1][2][3] that the airway epithelium is a barrier to the movement of low molecular weight hydrophilic compounds. However, recent studies in vivo measuring the movement of 99m technetium-diethylenetriamine penta-acetic acid ( 99m Tc-DTPA, a low molecular weight hydrophilic tracer of similar size to many drugs given by inhalation) from the tracheal lumen to venous blood suggest that the relevance of in vitro studies on permeability may be limited, for two reasons.Firstly, damage to the sheep tracheal epithelium in vivo increased the permeability coefficient of 99m Tc-DTPA (PDTPA) by a factor of 120 [4], a much greater change than that found in vitro using this tracer or other solutes of similar molecular weight [1][2][3]. This may be because the presence of a functional subepithelial capillary bed results in the sweeping away of the tracer in the bloodstream, thus altering both the flux and the concentration gradient of the tracer between tracheal lumen and the mucosa. Secondly, PDTPA is also greatly affected by changes in blood flow [5]. A negative relationship exists between venous 99 Tc-DTPA uptake and blood flow. The reason is unknown but may be related to changes in capillary fluid flux.Bronchoconstrictor agents, such as methacholine and histamine, cause vasodilatation, and when injected into the tracheal circulation markedly decrease PDTPA [5]. These drugs are often given by inhalation in provocation testing; asthmatics show an increased sensitivity, as measured by lung function tests [6,7]. This may be due, at least in part, to an increase in drug penetratio...