奥普力农对戊巴比妥麻醉犬高碳酸血症诱导的膈肌收缩力损伤的剂量相关效应。

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

作者信息

Fujii Yoshitaka, Uemura Aki

机构信息

First Department of Anesthesiology, Toho University School of Medicine, Tokyo, Japan.

Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

出版信息

Curr Ther Res Clin Exp. 2008 Jun;69(3):243-51. doi: 10.1016/j.curtheres.2008.06.006.

DOI:10.1016/j.curtheres.2008.06.006

PMID:24692802

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3969946/

Abstract

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.

摘要

背景

在之前的一项研究中，发现奥普力农在改善犬高碳酸血症引起的膈肌收缩力抑制方面比米力农更有效。

目的

本实验研究的目的是评估奥普力农对高碳酸血症诱导的膈肌收缩力损害的剂量相关效应。

方法

本研究在日本筑波大学临床医学研究所麻醉科进行。通过向戊巴比妥麻醉的犬吸入气体中添加10%二氧化碳来诱导高碳酸血症（动脉血二氧化碳分压[CO₂]为80 - 90 mmHg）。当建立高碳酸血症后，将犬随机分为4组中的1组：（所有犬均静脉注射10 mg/kg的奥普力农推注剂量）第1组用0.1 μg/kg·min⁻¹的奥普力农维持；第2组用0.3 μg/kg·min⁻¹的奥普力农维持；第3组用0.5 μg/kg·min⁻¹的奥普力农维持；第4组不接受研究药物。研究药物静脉注射60分钟。通过跨膈压（Pdi）评估膈肌收缩力。研究调查人员未对治疗分配进行盲法处理。

结果

本研究使用了24只健康成年杂种犬；每组分配6只犬。在每组存在高碳酸血症的情况下，低频（20 Hz）和高频（100 Hz）刺激时的Pdi（均值[标准差]，cm H₂O）较基线显著降低（均为，P = 0.001）。在第1、2和3组研究药物给药期间，两种刺激水平下的Pdi均较高碳酸血症诱导值显著增加（均为，P = 0.001）；在第4组中，每种刺激下的Pdi与高碳酸血症诱导值相比无显著变化。奥普力农剂量与两种刺激下的Pdi之间存在显著相关性（均为，P = 0.001）。回归方程为：20 Hz刺激时的Pdi（cm H₂O）= 24.97×奥普力农剂量（μg/kg·min⁻¹）+ 13.54（r = 0.887；n = 24），100 Hz刺激时的Pdi（cm H₂O）= 29.18×奥普力农剂量（μg/kg·min⁻¹）+ 20.55（r = 0.911；n = 24）。