BACKGROUND: Diaphragm fatigue (DF) has been implicated in respiratory failure in diseases that increase inspiratory resistance loading (IRL) and may complicate weaning of patients from mechanical ventilation. OBJECTIVE: The purpose of this study was to examine the effects of dobutamine administration (10 micro g/kg/min) on DF and to identify the mechanisms by which dobutamine augments diaphragm shortening and diaphragm blood flow (DBF) during fatigue with a rat model. METHODS: The study had an experimental design with 3 groups of Sprague-Dawley rats (n = 38) with 4 experimental periods: period 1, control; period 2, application of IRL; period 3, treatment; and period 4, recovery. DF was produced via IRL. During period 3 treatment, normal saline solution was infused in group I, dobutamine in group II, and dobutamine plus butoxamine hydrochloride in group III. The percent change in fractional diaphragm thickness (FDT) during inspiration reflected diaphragm shortening. DBF and aortic blood flow were determined with fluorescent microspheres. Diaphragm vascular resistance and systemic vascular resistance were calculated on the basis of Poiseuille's equation. RESULTS: Results indicated infusion of dobutamine increased FDT (P =.01) and DBF (P =.009) with respect to fatigue levels. The effects of dobutamine on FDT and DBF were attenuated with infusion of butoxamine hydrochloride (a beta-2 adrenoceptor antagonist) with respect to fatigue. CONCLUSION: Administration of dobutamine at a rate similar to that used clinically increased diaphragm muscle contractility (FDT) and DBF in diaphragms fatigued by IRL. The dobutamine effect on FDT may be the result of restoration of the balance between diaphragm energy consumption and energy delivery to the diaphragm by increasing DBF. Butoxamine hydrochloride attenuated the dobutamine-induced increase in DBF, indicating dobutamine produced vasodilatation via beta-2 adrenoceptors. Thus, the administration of intravenous dobutamine may be a useful adjunct in the treatment of DF.