We have recently developed a noninvasive dimethylether (DME) uptake technique to estimate airway mucosal blood flow (Qaw) in humans (12). Because it was not feasible to validate the technique directly, we undertook the present study to compare Qaw as measured by DME (QDME) and by color-coded microspheres (QM) as a standard in seven anesthetized sheep prepared with a carotid and a left atrial catheter. QDME was determined by measuring DME uptake with multiple breath holds after passive inflation with a DME-helium gas mixture, simulating the technique used in humans. After the microspheres were injected into the left atrium, the sheep were killed and the tracheal segment corresponding to the dead space from which DME uptake was determined was removed, and its mucosa was stripped and processed for microsphere counts. Mean QDME was 35.6 ml.min-1.100 g-1 wet tissue (range 9.6-98.0 ml.min-1.100 g-1) and mean QM was 29.1 ml.min-1.100 g-1 (range 7.7-91.5 ml.min-1.100 g-1). There was a strong correlation between QDME and QM (r = 0.89; P = 0.01). Intravenous nitroglycerin and vasopressin caused comparable increases and/or decreases in QDME and QM (r = 0.87; P = 0.02). This suggests that the noninvasive DME uptake method measures Qaw accurately and supports its validity in human studies.

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.

We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance (R(rs)) and inspiratory static respiratory system compliance (C(rs)) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. R(rs) responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC(150)) and intravenous spasmogen dose (PD(150)) causing an increase in R(rs) to 150% of baseline. C(rs) responsiveness was calculated similarly for a decrease in C(rs) to 85% of baseline (PC(85) for inhaled and PD(85) for intravenous spasmogen). Baseline R(rs) and C(rs) were similar in all groups. R(rs) responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains. In contrast, C(rs) responses were variable and had a greater mean PC(85) for inhaled serotonin than carbachol in both strains and a greater fall in mean C(rs) at PC(150) for carbachol in Balb/C mice; no interstrain and interdrug differences in PD(85) were noted for intravenous spasmogens. Intravenous atropine attenuated the R(rs) response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine attenuated C(rs) responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil.