Dose-related effects of olprinone on hypercapnia-Induced impairment of diaphragmatic contractility in pentobarbital-anesthetized dogs

Background: In a previous study, olprinone was found to be more effective than milrinone in improving hypercapnic depression of diaphragmatic contractility in dogs.Objective: The purpose of this experimental study was to assess the doserelated effects of olprinone on hypercapnia-induced impairment of diaphragmatic contractility.Methods: This study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Hypercapnia (partial pressure of carbon dioxide [C02] in arterial blood 80-90 mm Hg) was induced in pentobarbital-anesthetized dogs by adding 10% C02 to their inspired gas. When hypercapnia was established, the dogs were randomly assigned to 1 of 4 groups: (all dogs were administered a bolus dose of olprinone 10 mg/kg) group 1 was maintained with olprinone 0.1 μg/kg · min-1; group 2 was maintained with olprinone 0.3 μg/kg · min-1; group 3 was maintained with olprinone 0.5 μg/kg min-1; and group 4 received no study drug. The study drug was administered IV for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi). The study investigator was not blinded to treatment assignment.Results: Twenty-four healthy adult mongrel dogs were used in the study; 6 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 (all, P = 0.001). During study drug administration in groups 1, 2, and 3, Pdi at both stimuli levels increased significantly from hypercapnia-induced values (all, P = 0.001); in group 4, Pdi to each stimulus did not change significantly from hypercapnia-induced values. There was a significant correlation between olprinone dose and Pdi at both stimuli (all, P = 0.001). The regression equations were: Pdi at 20-Hz stimulation (cm H2O) = 24.97 × olprinone dose (μg/kg · min-1) + 13.54 (r = 0.887; n = 24) and Pdi at 100-Hz stimulation (cm H2O) = 29.18 × olprinone dose (μg/kg · min-1) + 20.55 (r = 0.911; n = 24).Conclusion: Olprinone was associated with a dose-dependent improvement of hypercapnia-induced impairment of diaphragmatic contractility in these pentobarbital-anesthetized dogs.