Abstract.
BACKGROUND: 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 1 received no study
drug, group 2 was infused with
milrinone (50 g/kg initial dose plus 0.5 g/kg · min(-1) thereafter), and group 3 was infused with
olprinone (10 g/kg initial dose plus 0.3 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 highfrequency (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 [2.3], 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.