Effects of β2-agonists on the contractility of fatigued canine diaphragm in vivo

Abstract

We examined the effects of four β 2-agonists, clenbuterol, metaproterenol, procaterol, and albuterol, on the contractility of fatigued canine diaphragm. Diaphragmatic contractility was assessed from changes in transdiaphragmatic pressure (Pdi) generated by supramaximal electrical stimulation of the phrenic nerve. Diaphragmatic fatigue was developed by applying an inspiratory resistive load to spontaneously breathing dogs for 30–50 min. Four doses of each β 2-agonist were intravenously administered to dogs when the decreased Pdi became stable. Clenbuterol increased Pdi at doses of 10 and 20 μ/kg ( P<0.05). Metaproterenol improved Pdi of the fatigued diaphragm at low stimulation frequencies in a dose-dependent manner ( P<0.05). Procaterol increased Pdi at a low dose but decreased Pdi at higher doses, possibly due to a marked decrease in systemic blood pressure. Albuterol did not change Pdi at any dose. These results suggest that both clenbuterol and metaproterenol have a positive inotropic effect on fatigued canine diaphragm, while procaterol has a negative effect at high doses. Albuterol showed no inotropic effect.