Effects of Theophyllme on Pharyngeal Dilator and Diaphragm Muscle Contractile Properties

Abstract

Theophylline alleviates central and obstructive apneas of prematurity, and may improve adult obstructive sleep apnea. One mechanism of action appears to be a stimulatory effect on the motor output to upper airway dilator muscles. The purpose of the present study was to determine whether theophylline might have a second mechanism of action, namely that of improving the force and/or endurance of the pharyngeal dilator musculature. Rat sternohyoid muscle strips were studied in vitro and compared to diaphragm strips. The isometric twitch force and twitch kinetics of neither muscle were altered by theophylline (100 mg/l). Theophylline significantly slowed the rate at which the diaphragm fatigued during intermittent 40-Hz stimulation (p < 0.001). In contrast, theophylline produced no improvement in the fatigue resistance of the sternohyoid muscle. The degree of force potentiation during the early portion of the fatigue protocol was not altered by theophyllme for either muscle. These results suggest that the mechanism by which theophylline improves obstructive apnea is unlikely to be due to a beneficial effect on pharyngeal dilator muscle force or endurance.

Structural and Functional Properties of an Upper Airway Dilator Muscle in Aged Obese Male Rats

“…Retropharyngeal fat pads may predispose to airway obstruction, and aging of airway musculature may weaken their ‘splinting’ action on the upper respiratory tract. Previous studies on the aged Fisher rat [4] and the Zucker fatty rat [5,6] have examined these factors in isolation and found no effect on peak force production, but the combination of these factors may overwhelm the working muscle. Therefore, we decided to study the structure and function of an upper airway dilator muscle (sternohyoid) in young lean and old obese male rats.…”

Theβ2‐adrenoceptor agonist terbutaline recovers rat pharyngeal dilator muscle force decline during severe hypoxia

“…Pharmacological intervention for OSAS is considered a viable clinical option (Hudgel and Thanakitcharu, ; Veasey, , ). Agents, such as nicotine, K + channel blockers, theophylline, almitrine, aminophyline, 5HT, and antioxidants, such as tempol, tiron, NAC and apocynin, have been examined (Howell et al , ; Viires et al , ; Reid and Miller, ; Van Lunteren et al , , ; O'Halloran et al , ; O'Halloran, ; Skelly et al , ; Shortt et al , ) as a means of increasing muscle function. Notwithstanding that airway obstruction in OSAS results from sleep‐related reductions in neural drive to UA dilator muscles, agents that improve UA muscle force, in addition to those increasing cranial motor drive, may be of clinical importance.…”