Effects and Mechanism of Fenoterol on Fatigued Canine Diaphragm

Abstract

We have studied the effects and mechanism of fenoterol (a beta 2-agonist) on contractility of the fatigued canine diaphragm. Transdiaphragmatic pressure (Pdi) was measured by a pair of balloons, and diaphragmatic contractility was assessed from changes in tetanic contraction, produced by supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic fatigue was developed by applying an inspiratory resistive load to a spontaneously breathing dog for approximately 30 min. Fenoterol improved the Pdi of the fatigued canine diaphragm at all stimulation frequencies, and the increases in Pdi at low frequencies were greater. The potentiation of Pdi by fenoterol occurred in a dose-dependent manner with doses of 2.5 to 10 micrograms/kg and was equal to that of aminophylline. Dibutyryl cyclic AMP did not have significant effect on the Pdi at all stimulation frequencies. The augmentation of Pdi in the fatigued diaphragm by fenoterol was abolished by administration of a calcium antagonist, verapamil, and fenoterol did not change the diaphragmatic contractility in nonfatigued dogs. We thus have concluded that fenoterol improves contractility in the fatigued canine diaphragm and the effect might be brought about by an increased influx of calcium to the muscle cell.

Failure of Aminophylline and Salbutamol to Improve Respiratory Muscle Function and Exercise Tolerance in Healthy Humans

“…Fenoterol [8] and terbutaline [2] have been demonstrated to enhance the contractility of the diaphragm in dogs but not in chronic obstructive pulmonary dis ease (COPD) [29]. Salbutamol in dogs [6,24] and in humans [25] showed no or small effects.…”

β2-Agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol

“…In isolated human papillary muscle preparations, fenoterol exerts a direct positive inotropic effect in the heart mediated by ␤ 1 -and ␤ 2 -adrenoceptors (30). Acute intravenous administration of fenoterol to anesthetized dogs did not affect diaphragm muscle contractility in the resting state, but it did improve contractility during fatigue (43). Fenoterol given to lambs in their food for 8 wk did not increase the mass of their infraspinatus or pectoralis profundus muscles (13).…”

Tulobuterol Patch Maintains Diaphragm Muscle Contractility for Over Twenty-four Hours in a Mouse Model of Sepsis

“…It is well known that β 2 -adrenergic receptor agonists, such as isoproterenol (Howell and Roussos 1984), fenoterol (Suzuki et al 1986), terbutaline (Cairns and Dulhunty 1993) and clenbuterol (Heijden et al 1997), increase diaphragm muscle contractility. It has also been reported that diaphragm weakness occurs in patients with mild to moderate bronchial asthma (Akkoca et al 1999;Barbarito et al 2001;Weiner et al 2002).…”