Effects of PDE3 Inhibitor Olprinone on the Respiratory Parameters, Inflammation, and Apoptosis in an Experimental Model of Acute Respiratory Distress Syndrome.

Petra Kosutova,Pavol Mikolka,Marian Adamkov,Andrea Calkovska,Daniela Mokra,Sona Balentova

doi:10.3390/ijms21093382

Abstract

This study aimed to investigate whether a selective phosphodiesterase-3 (PDE3) inhibitor olprinone can positively influence the inflammation, apoptosis, and respiratory parameters in animals with acute respiratory distress syndrome (ARDS) model induced by repetitive saline lung lavage. Adult rabbits were divided into 3 groups: ARDS without therapy (ARDS), ARDS treated with olprinone i.v. (1 mg/kg; ARDS/PDE3), and healthy ventilated controls (Control), and were oxygen-ventilated for the following 4 h. Dynamic lung–thorax compliance (Cdyn), mean airway pressure (MAP), arterial oxygen saturation (SaO2), alveolar-arterial gradient (AAG), ratio between partial pressure of oxygen in arterial blood to a fraction of inspired oxygen (PaO2/FiO2), oxygenation index (OI), and ventilation efficiency index (VEI) were evaluated every hour. Post mortem, inflammatory and oxidative markers (interleukin (IL)-6, IL-1β, a receptor for advanced glycation end products (RAGE), IL-10, total antioxidant capacity (TAC), 3-nitrotyrosine (3NT), and malondialdehyde (MDA) and apoptosis (apoptotic index and caspase-3) were assessed in the lung tissue. Treatment with olprinone reduced the release of inflammatory mediators and markers of oxidative damage decreased apoptosis of epithelial cells and improved respiratory parameters. The results indicate a future potential of PDE3 inhibitors also in the therapy of ARDS.

Highlights

Acute respiratory distress syndrome (ARDS) is a common clinical disease that involves widespread inflammation in lung tissue, which is the first step in the development of lung dysfunction [1]
Anti-oxidant enzymes, such as catalase (CAT) or superoxide dismutase (SOD) can ameliorate this adverse condition [7]. These findings suggest that targeting the inflammation and/or oxidative stress could be a potential strategy to improve ARDS
This study aimed to investigate whether PDE3 inhibitor olprinone can positively influence the inflammation, apoptosis, and respiratory parameters in another model of ARDS induced by repetitive saline lung lavage

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a common clinical disease that involves widespread inflammation in lung tissue, which is the first step in the development of lung dysfunction [1]. The cardinal pathophysiologic features of ARDS include dysregulated inflammation and alveolar-capillary barrier disruption [4]. These are represented histologically by (a) neutrophilic alveolitis, (b) deposition of hyaline membranes in the alveoli, and (c) formation of microvascular thrombi, indicating activation of the coagulation cascade and endothelial damage [5]. Anti-oxidant enzymes, such as catalase (CAT) or superoxide dismutase (SOD) can ameliorate this adverse condition [7]. These findings suggest that targeting the inflammation and/or oxidative stress could be a potential strategy to improve ARDS

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Methods

Conclusion