Effect of inhaled and intravenous acetylcholine on bronchial blood flow in anesthetized sheep

Abstract

The reported effects of cholinergic agonists on bronchial blood flow (Qbr) have been inconsistent. The aim of the present study was to determine whether the inconsistency could be due to the mode of agonist administration (systemic vs. aerosol) or the anatomic site of blood flow in the bronchus (mucosal vs. deep wall). In 10 anesthetized mechanically ventilated adult sheep, we measured Qbr in main bronchi by color-coded microspheres, systemic and pulmonary arterial pressures, cardiac output, and lung resistance (RL) before and after acetylcholine (ACh) administered either as an aerosol (nebulized dose 100 micrograms) or as an intravenous bolus (2 micrograms/kg). Before drug administration, 72% of mean Qbr was distributed to the bronchial mucosa and the remainder was distributed to the deep bronchial wall. For a comparable increase in mean RL (150% for intravenous ACh and 205% for aerosol ACh), mean total Qbr normalized for systemic arterial pressure increased by 291% after intravenous ACh (P < 0.05) and decreased by 9% after aerosol ACh (not significant). Mucosal and deep wall Qbr increased proportionally. Atropine (0.2 microgram/kg) prevented the changes in Qbr and RL after intravenous ACh. Thus intravenous but not aerosol ACh increased blood flow in the mucosa and deep wall of extrapulmonary bronchi. This suggests that the muscarinic receptors mediating vasodilation are more accessible to intravascular than intrabronchial ACh.

Differential effects of inhaled methacholine on circumferential wall and vascular smooth muscle of third-generation airways in awake sheep

“…The current studies using direct measurement of bronchial dimensions extend the findings of Charan et al (10) and Scuri et al (35), who found that cholinoceptor agonists by either inhaled or intravascular routes caused a rise in whole-lung airflow resistance. In the current study, both inhaled and iv MCh cause dose-related airway wall circular smooth muscle constriction, and the plateau effects at the highest doses indicate that maximum circumferential shortening of the bronchus by each route is the same at 10%.…”

“…The finding of differential engagement of the bronchovascular bed by the different access routes also extends studies in anesthetized sheep (9,10,35). It has been suggested (10) that airway wall contraction following inhalation of MCh may not be by direct action across the airway wall but by indirect mechanisms following initial penetration of the mucosal bronchovascular bed by MCh, followed by systemic recirculation.…”

“…It has been argued that airway circular wall contraction is primary to inhaled MCh epithelial absorption and that the absence of C br change is a zero-sum effect, e.g. at low doses a direct, limited vascular wall penetration and vasoconstriction, offset at higher doses by a more measured penetration to the endothelium and vasodilatation (35). An alternative (10) proposed is complete penetration of the bronchovascular bed, systemic recirculation and a conductance balance struck indirectly by an activated endothelium.…”

Lung Circulation

“…As might be expected from results in other systemic circulations, NO (100, 420) and PGI 2 (132) have each been shown to increase the bronchial blood flow. Intravenous administration of acetylcholine also vasodilates the bronchial circulation (543,558), as does histamine (334,358,370). Interestingly, ET-1 also dilated bronchial arteries when administered intravenously (402,607), perhaps due to activation of endothelial ET B receptors.…”

The bronchial circulation—worth a closer look: A review of the relationship between the bronchial vasculature and airway inflammation

“…[8][9][10] This submucosal microvascular network receives between 60% and 85% of the total bronchial blood flow. 11,12 Venous drainage of the proximal conducting airway (first two divisions) follows the same pattern as the arterial supply, with blood being returned to the right heart via the azygos and hemiazygos veins. More distally the bronchial microvasculature anastomoses with the pulmonary circulation and is often referred to as the ''bronchopulmonary anastomotic'' flow or the ''pulmonary collateral'' circulation.…”