Tohoku J. Exp. Med., 2007, 212(3)

Transdermal Treatment with Tulobuterol Increases Isometric Contractile Properties of Diaphragm Muscle in Mice

CHIYOHIKO SHINDOH,¹ RINA TSUSHIMA,¹ YURIKO SHINDOH² and GEN TAMURA³

¹Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University, Sendai, Japan
²Department of Respiratory Medicine, Sendai City Medical Center, Sendai, Japan
³Department of Infection and Respiratory Medicine, Tohoku University Hospital, Sendai, Japan

Clinically, patients suffering from bronchial asthma are often treated transdermally with tulobuterol patches to dilate the bronchi. Tulobuterol, a synthetic β₂ agonist, is also thought to act as a diaphragm muscle contractor, like other β₂ sympathomimetic drugs. However, it has not been clarified that transdermal treatment with tulobuterol influences diaphragm muscle contractility. We therefore examined its effects on contractile properties of such muscles obtained from BALB/c mice. Two systems, a tulobuterol incubation group (in vitro) and a tulobuterol transdermal treatment group (in vivo), were employed. In both groups, the contractile properties of the dissected diaphragm muscles were measured by field stimulation in an organ bath. In the incubation group, the diaphragm muscle of untreated mice was incubated in an organ buffer at 10^-7, 10^-6, or 10^-5 M tulobuterol for 1 hr and then measured for contractility. Tulobuterol significantly increased force-frequency curves at a concentration of 10^-5 M at 1 (p < 0.01), 30, 50, 70, 100, and 120 Hz (p < 0.05, each) compared with the values at 0 M. In the transdermal treatment group, the diaphragm muscle was dissected from animals at 1, 4, 8, 12, or 24 hrs after treatment and measured for contractility, showing that the force-frequency curves were significantly increased and maintained from 4 to 24 hrs (each p < 0.01 as compared with the sham-treated group). We suggest that transdermal tulobuterol treatment in case of bronchial asthma is useful not only for bronchial dilatation, but also for increasing diaphragm muscle contractility.

keywords —— β₂-agonists; diaphragm muscle; muscle contractility; transdermal treatment; COPD

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 212, 309-317

Correspondence: Chiyohiko Shindoh, M.D., Prof., Department of Medical Technology, Faculty of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.

e-mail: cshindoh@mail.tains.tohoku.ac.jp