Can Damage to the Rat Lung Induced by Prolonged Normobaric Hypoxia and Norepinephrine Be Reversed by Normoxic Recovery?

TL;DR

This study investigates whether lung damage from hypoxia and norepinephrine can be reversed with normoxic recovery in rats.

Contribution

The study reveals that normoxic recovery does not reverse hypoxia-induced pulmonary edema despite reducing inflammation and oxidative stress.

Findings

Pulmonary edema did not resolve after three days of normoxic recovery.

Protein concentrations in pleural and bronchoalveolar lavage fluids increased during recovery.

Inflammation and oxidative stress decreased during normoxic recovery.

Abstract

Exposure to hypoxia may cause lung injury characterized by hydrostatic pulmonary edema (PE), inflammation and oxidative stress. Norepinephrine (NE) infusion can also induce lung injury with similar pathogenetic characteristics. The main questions of this study were (i) whether NE infusion aggravates hypoxia-induced pulmonary injury; (ii) whether inflammation and oxidative stress deteriorate the hypoxic PE; and (iii) whether PE and inflammation recede after three days of normoxic recovery. Ninety-eight female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl or NE. Some of these animals were transferred to a three-day normoxic recovery period thereafter. We performed histological and immunohistochemical analyses of the lung, determined protein concentrations in pleural fluid (PF) and bronchoalveolar lavage fluid (BALF), and evaluated hemodynamic parameters. While inflammation and oxidative stress receded after 3 days of normoxic recovery, PE did not resolve. Increased protein concentrations in PF and BALF indicated that capillary stress failure increased even further during the normoxic recovery phase, particularly in animals that had previously received an NE infusion. These results highlight the fact that inflammation does not play a causal role in the development of hypoxic PE.

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