Inhaled olprinone improves contractility of fatigued canine diaphragm

Abstract

Background. Diaphragmatic fatigue is implicated as a cause of respiratory failure. This study was undertaken to evaluate the effects of inhaled olprinone, a newly developed phosphodiesterase III inhibitor, on the contractility of fatigue diaphragm in dogs. Methods. Diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz stimulation applied for 30 min. When fatigue was established, group I (n=8) received inhaled vehicle; group II (n=8) received inhaled olprinone I mg; group III (n=8) received inhaled olprinone 2 mg. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi, cm H2O). Results. In the presence of fatigue, in each group, Pdi at low-frequency (20 Hz) stimulation decreased from baseline values (P<0.05), whereas Pdi at high-frequency (100 Hz) stimulation did not change. In groups II and III, during olprinone administration, Pdi at both stimuli increased from fatigued values (20 Hz stimulation: group II (mean (SD)) 10.8 (1.0) to 12.5 (1.3), group III 10.9 (1.7) to 15.0 (3.0); 100 Hz stimulation: group II 20.1 (1.9) to 22.6 (1.3), group III 20.6 (2.0) to 24.5 (2.0), P<0.05). The increase in Pdi was larger in group III than in group II (P<0.05). Conclusions. Inhaled olprinone produces a dose-dependent improvement in contractility of fatigued canine diaphragm.