Respiratory muscle fatigue, especially that of the diaphragm muscle, has been implicated in the progression of respiratory failure. Patients with acute respiratory failure are mechanically ventilated and given other supportive measures designed to decrease the need for mechanical ventilatory support. Removal of ventilatory support is termed weaning the patient. As patients are weaned diaphragm fatigue often develops which impedes successful weaning and prolongs the course of mechanical ventilation. It has been observed that the sympathomimetic agent dobutamine increased the contractility of the fatigued diaphragm. It is not known whether this effect of dobutamine is due to: 1) an increased diaphragm blood flow secondary to the positive inotropic effect of the drug on the heart; 2) the drug relaxing vascular smooth muscle and thereby increasing diaphragm blood flow; and/or 3) dobutamine binding to beta-2 receptors on diaphragm muscle and directly increasing contractility. The proposed experiments will indicate which of these is the most prevalent mechanism by which dobutamine increases diaphragm performance. The results will indicate the merit of using more specific pharmacological agents for patients experiencing diaphragm fatigue.
| Smith-Blair, Nan J; Pierce, Janet D; Clancy, Richard L (2003) The effect of dobutamine infusion on fractional diaphragm thickening and diaphragm blood flow during fatigue. Heart Lung 32:111-20 |
