Inhaled milrinone for the improvement of contractility of fatigued diaphragm in dogs: a dose-ranging study

The present study was undertaken to evaluate the efficacy of inhaled milrinone on contractility of fatigued diaphragm in dogs. Animals were divided into four groups of seven each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Immediately after the end of a fatigue-producing period, Group I received inhaled vehicle; Group II received inhaled milrinone 0.1 mg/ml (1 mg); Group III received inhaled milrinone 0.2 mg/ml (2 mg); Group IV received 0.5 mg/ml (5 mg). Study drug was administered for 30 min. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20 Hz) decreased from baseline values (P < 0.05), and Pdi at high-frequency (100 Hz) stimulation did not change. In Groups III and IV, during milrinone inhalation, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was more in Group IV than in Group III (P < 0.05). Compared with Group I, Pdi to each stimulus did not change in Group II. In conclusion, inhaled milrinone, in doses more than 0.2 mg/ml, is effective for improving contractility of fatigued diaphragm in dogs. (C) 2004 Elsevier Ltd. All rights reserved.