Differential bronchodilatory effects of terbutaline, diltiazem, and aminophylline in canine intraparenchymal airways.

OBJECTIVES: Intraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics. DESIGN: In vitro, controlled, randomized study. SETTING: Animal research laboratory. SUBJECTS: Adult dogs (n = 9). INTERVENTIONS: Proximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10(-8) to 10(-4) M), diltiazem (concentration range, 3 x 10(-7) to 1 x 10(-4) M), and aminophylline (concentration range, 10(-7) to 10(-4) M). MEASUREMENTS AND MAIN RESULTS: All three bronchodilators caused relaxation of the proximal and distal airways. At the maximum dose, diltiazem (maximum relaxation, 95%+/-2% [proximal], 94%+/-6% [distal]; p > .05) was the most efficacious, followed by terbutaline (maximum relaxation, 72%+/-13% [proximal], 55%+/-9% [distal]; p < .05) and aminophylline (maximum relaxation, 32%+/-10% [proximal], 35%+/-18% [distal]; p > .05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range. CONCLUSIONS: The results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics.

Direct relaxant effects of intravenous anesthetics on airway smooth muscle.

Ketamine, at concentrations achieved with the usual clinical doses, has a direct relaxant effect on airway smooth muscle (ASM). This study investigates the dose-dependent direct relaxation effects of midazolam and propofol on both proximal and distal ASM compared with ketamine. The proximal and distal airways were dissected from eight mongrel dogs and cut into 2-mm rings. The rings were attached to pressure transducers and equilibrated in a Krebs-Ringer bicarbonate bath kept at 37 degrees C, pH 7.4, CO2 37 mm Hg, and PaO2 > 100 mm Hg. Optimal length was determined, a dose-response curve to acetylcholine was established, and the 50% effective dose (ED50) of acetylcholine was calculated. Ketamine, midazolam, or propofol were given in random order to each ring preconstricted with ED50 of acetylcholine in cumulative log incremental doses from 10(-6) to 10(-4) M. Relaxation response was the tension during anesthetic equilibrium, expressed as a percentage of the tension from ED50 of acetylcholine. The drug vehicles were tested for their effects on the ASM. No bronchorelaxation was seen with any of the intravenous anesthetics at 10(-6) M. Ketamine 10(-5) M produced at 17.9% +/- 2.1% relaxation in the distal ASM but had no effect on the proximal ASM. Neither propofol nor midazolam affected the ASM at 10(-5) M. The distal ASM was significantly (P < 0.005) more sensitive to 10(-4) M of all three drugs compared with the proximal ASM. In the proximal ASM, 10(-4) M of ketamine, midazolam and propofol reduced ASM tension by 14.9% +/- 4.4%, 19.0% +/-8.8%, and 14.7% +/- 5.5%, respectively, versus 36.4% +/- 3.2%, 58.6% +/- 6.1%, and 64.4% +/- 9.0% in the distal ASM. The drug vehicles had no effect on the ASM. We conclude that ketamine, midazolam, and propofol have direct relaxant effects on ASM. All three intravenous anesthetics have a greater direct relaxant effect on distal ASM than on proximal ASM. Only ketamine showed significant direct bronchorelaxing effects at concentrations that are likely to be achieved with the usual clinical dosing patterns.

Differential effects of desflurane and halothane on peripheral airway smooth muscle.

Volatile anaesthetics have been shown to have direct relaxant effects on airway smooth muscle. We have examined the effects of 0.9, 1.9, and 2.8 dog MAC of desflurane and halothane on isolated proximal and distal canine airways precontracted with acetylcholine. The proximal and distal airway smooth muscle relaxed with increasing concentration of each anaesthetic in a dose-related manner. Desflurane had a greater relaxant effect than halothane on the proximal airway only at 2.8 MAC. Desflurane relaxed the distal airway to a greater extent than halothane at 1.9 and 2.8 MAC. The distal airway smooth muscle was more sensitive to volatile anaesthetics than the proximal airway smooth muscle with either halothane or desflurane at all concentrations tested. This effect may be a result of differences in cartilage content, myosin content, epithelium-dependent effects, receptor density, myofilament sensitivity to Ca2+, sarcoplasmic reticulum Ca2+ control, or ionic fluxes in the proximal airway compared with the distal airway. The increased sensitivity of airway smooth muscle to desflurane compared with halothane is not known but may be related to possible differences in the effects of Ca2+ homeostasis.

Sedation for the mechanically ventilated patient.

This article discusses the potential benefits of sedation for the mechanically ventilated patient. These benefits include the alleviation of anxiety and pain, which may result in a reduction of oxygen consumption. Other advantages include improved synchronization of a patient's breathing pattern with ventilator settings and better patient care, comfort, and safety. The patient's clinical situation, such as respiratory failure caused by right-to-left shunt, cardiovascular problems, elevated intracranial pressure, hepatic disease, and renal failure, needs to be considered when selecting a sedative agent.

Topographical differences in the direct effects of isoflurane on airway smooth muscle.

Volatile anesthetics have a direct relaxant effect on airway smooth muscle, but it is not known whether this effect is similar throughout the bronchial tree. We studied the direct relaxation effect of isoflurane on isolated proximal (outer diameter [OD] 4-6 mm) and distal (OD 0.7-1.5 mm) canine airways precontracted with acetylcholine. Proximal and distal airway rings were suspended in tissue baths and stretched to their optimum length. A dose-response curve was obtained for each airway ring with log increments of acetylcholine. Maximum contraction was reached with 10(-2) mol/L of acetylcholine for the proximal airway smooth muscle (7.0 +/- 0.3 g of tension) and 10(-3) mol/L of acetylcholine for the distal airway smooth muscle (2.3 +/- 0.1 g of tension). Based on the dose-response curve, the ED50 of acetylcholine was calculated (1.26 +/- 0.37 x 10(-4) mol/L for proximal airway smooth muscle; 2.12 +/- 1.14 x 10(-5) mol/L for distal airway smooth muscle) and administered to each tissue bath, after which the stabilized response was recorded. A randomly selected dose of isoflurane (1, 2, or 2.6 dog minimum alveolar anesthetic concentration [MAC] was then administered to each bath and the relaxant responses were recorded. The proximal and distal airways relaxed with increased doses of isoflurane in a dose-related manner.