Effects of milrinone and olprinone on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs

Background: Hypercapnia is associated with diaphragm muscle dysfunction that is a reduction of diaphragmatic force generated for stable electric myographic activity. Objective: The purpose of this study was to test the effects of milrinone and olprinone on decreased diaphragmatic contractility induced by hypercapnia in pentobarbital-anesthetized dogs. Methods: This experimental study was conducted at the Department of Anesthesiology, University of Tsukuba, Institute of Clinical Medicine, Tsukuba, Japan. Hypercapnia (partial pressure of carbon dioxide [CO2] in arterial blood 80-90 mm Hg) was induced by adding 10% CO2 to the inspired gas. When hypercapnia was established, group I received no study drug, group 2 was infused with milrinone (50 mu g/kg initial dose plus 0.5 mu g/kg . min(-1) thereafter), and group 3 was infused with olprinone (10 mu g/kg initial dose plus 0.3 mu g/kg . min(-1) thereafter). Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). Results: Twenty-four, healthy, adult mongrel dogs were used in the study; 8 dogs were assigned to each treatment group. In the presence of hypercapnia, in each group, Pdi (mean [SD], cm-H2O) at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation significantly decreased from baseline (group 1: 20 Hz, 15.1 [2.4] vs 13.3 [2.7]; 100 Hz, 23.1 [2.7] vs 20.6 [2.5], both, P = 0.001; group 2: 20 Hz, 15.2 [2.0] vs 13.2 [2.5]; 100 Hz, 23.0 [2.5] vs 20.5 [2.5], both, P = 0.001; group 3: 20 Hz, 15.0 [2.2] vs 13.2 [2.1]; 100 Hz, 23.0 [2.5] vs 20.5 [2.7], both, P = 0.001). In group 1, the change in Pdi with regard to each stimulus was not significant when compared with the hypercapnia-induced values. In groups 2 and 3, during study-drug administration, Pdi increased significantly in response to both stimuli compared with hypercapnia-induced values (group 2: 20 Hz, 13.2 [2.5] vs 18.8 [2.2]; 100 Hz, 20.5 [2.5] vs 27.7 [2.3], both, P = 0.001; group 3: 20 Hz, 13.2 [2.1] vs 22.3 [3.5]; 100 Hz, 20.5 [2.7] vs 30.8 [2.2], both, P = 0.001). The increase in Pdi with both stimuli was significantly greater in group 3 than in group 2 (20 Hz, 22.3 [3.5] vs 18.8 [2.2], P = 0.035; 100 Hz, 30.8 [2.2] vs 27.7 [2.31, P = 0.046). Conclusions: The results of this experimental study of the effects of milrinone and olprinone on hypercapnic depression of diaphragmatic contractility in these pentobarbital-anesthetized dogs suggest that olprinone and milrinone significantly improved diaphragm muscle dysfunction induced by hypercapnia. The effects of olprinone were significantly greater than those of milrinone. Further studies are needed to determine the optimal dose of the study drugs.