Original Article
Effects of Bupivacaine on the Isolated Rat Tracheal Smooth Muscle

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Background

Bupivacaine is an amide-linked local anesthetic that has been used in subcutaneous infiltration, epidural and peripheral nerve block for surgery over three decades. Several studies have suggested that inhaled local anesthetics can reduce respiratory reflexes. To assess the direct actions of bupivacaine on airway smooth muscle we used our preparation to examine the effectiveness of bupivacaine on isolated rat trachea.

Methods

A 5-mm-long portion of rat trachea was mounted in Krebs solution at 37 °C. Changes in tracheal contractility in response to a parasympathetic mimetic agent and electrical stimulation were measured using a transducer connected to a Pentium III computer equipped with polygraphy software. The following assessments were done: (1) effect of bupivacaine on the resting tension of tracheal smooth muscle; (2) effect of bupivacaine on contraction caused by exposure to 10−6 M methacholine as a parasympathetic mimetic; (3) effect of bupivacaine on electrically induced contraction of tracheal smooth muscle.

Results

Bupivacaine had a negligible effect on the basal tracheal tension as the concentration increased. Bupivacaine inhibited the tracheal smooth muscle contraction in response to methacholine and electrical stimulation in a concentration-dependent manner.

Conclusion

The study indicates that bupivacaine might inhibit cholinergic neurotransmission and have an anti-spasmic effect on the trachea, in that it inhibited the contractions elicited by electrical field stimulation and a depolarizing agent.

Introduction

Vascular or nasal mucosal strips have been used to study smooth muscle contractility in vitro.1, 2 Effects of drugs on the airway have been examined using a rat tracheal smooth muscle preparation because this tissue has a resting tone and pharmacological responses similar to those of the human airway. We developed a simple and rapid test for identifying agents that affect tracheal smooth muscle directly.3 The development of such a test could help resolve the inconsistencies observed in trachea responses to drugs in vivo.

Bupivacaine is an amide-linked local anesthetic that is usually used for infiltration, nerve block, epidural and intrathecal anesthesia. Bupivacaine acts by binding to the sodium channels and blocking sodium influx into nerve cells, which prevents depolarization of the nerve fibers. Some reports have shown that aerosol inhalation of local anesthetics can reduce cough, inflation and deflation reflexes, and facilitate tracheal intubation during surgical operations.4, 5, 6 Intravenous administration of lidocaine or bupivacaine has been reported to attenuate bronchial hyper-reactivity in awake humans.7 It has been demonstrated that bupivacaine or lidocaine applied topically to the smooth muscle of isolated rat tail arteries can inhibit vascular contraction in response to adrenergic activation.8 The effect of bupivacaine topically applied to the trachea has not been well explored. In the present study, we used a simple in vitro technique to investigate the direct effects of bupivacaine on the contractile response of isolated rat tracheal smooth muscle to methacholine and electric field stimulation (EFS).

Section snippets

Study design

This study was approved by the Animal Experiment Review Board (IACUC-08-146). All chemical reagents were obtained from Sigma (St Louis, MO, USA) and were of the highest purity available. Adult rats were anesthetized using intraperitoneal pentobarbital administration (45 mg/kg) and two pieces of trachea each ∼5 mm long were removed from each rat. Each specimen was mounted using two steel plates and immersed in a bath containing 30 mL of Krebs solution (118 mM NaCl, 4.7 mM KCl, 2.5 mM CaCl2,

Results

The degree of contraction or relaxation in tracheal strips was determined from the tension applied to the transducer. The addition of bupivacaine to the bath did not significantly alter the resting tension in non-stimulated tracheal strips (Figure 1).

Tracheal contraction induced by methacholine was easily detected and the tissue remained in a contracted state until the drug was rinsed from the tissue. When bupivacaine was cumulatively applied to the steady state of 10−6 M methacholine-induced

Discussion

Many in vitro assays have been used for investigating tracheal responses to local anesthetics or other drugs. In those assays, the tracheal preparation was opened by cutting through the cartilage rings or the tracheal mucosa was removed or only tracheal smooth muscle strips were used.9, 10, 11, 12, 13 All of these procedures violate the normal physiology in vivo. The tracheal strips used in our examination were excised as an intact trachea ring without damaging the mucosa or smooth muscle;

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Cited by (3)

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    Citation Excerpt :

    A passive tension of 0.3 g was applied to the strips, and subsequent changes in tension were recorded continuously using Chart V4.2 software (PowerLab; ADInstruments, Colorado Springs, Colorado, USA). A previous study showed that methacholine can induce a dose-dependent contraction of a tracheal strip, and that a concentration of 10−6 M can result in a significant contraction.10,11 Our preliminary test results showed that a tracheal strip immersed in the bath solution used for subsequent experiments did not contract when basal tension was applied.

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