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.