Mechanical ventilation restores blood gas homeostasis and diaphragm muscle strength in ketamine/medetomidine-anaesthetized rats.

NEW FINDINGS: What is the central question of the study? Does respiratory support ensure blood gas homeostasis and the relevance of experimental outcomes? What is the main finding and its importance? Spontaneous breathing during surgical intervention under anaesthesia results in impaired gas exchange and loss of diaphragm muscle strength in rats. Subsequent short-term mechanical ventilation restored blood gas homeostasis and diaphragm muscle strength. Blood gas homeostasis interferes substantially with experimental conditions and may alter study results. Monitoring and maintenance of blood gas balance is required to ensure quality and relevance of physiological animal experiments. ABSTRACT: In pre-clinical small animal studies with surgical interventions under general anaesthesia, animals are often left to breathe spontaneously. However, anaesthesia may impair respiratory functions and result in disturbed blood gas homeostasis. In turn, the disturbed blood gas homeostasis can affect physiological functions and thus unintentionally impact the experimental results. We hypothesized that short-term mechanical ventilation restores blood gas balance and physiological functions despite anaesthesia and surgical interventions. Therefore, we investigated variables of blood gas analyses and diaphragm muscle strength in rats anaesthetized with ketamine/medetomidine after tracheotomy and catheterization of the carotid artery under spontaneous breathing and after 20 min of mechanical ventilation following the same surgical intervention. Spontaneous breathing during general anaesthesia and surgical intervention resulted in unphysiological blood oxygen partial pressure (<65 mmHg) and carbon dioxide partial pressure (>55 mmHg). After subsequent short-term mechanical ventilation, blood gas partial pressures were restored to their physiological ranges. Additionally, diaphragm muscle strength of animals breathing spontaneously was lower compared to animals that received subsequent mechanical ventilation (P = 0.0063). We conclude that spontaneous breathing of rats under ketamine/medetomidine anaesthesia is not sufficient to maintain a physiological blood gas balance. Disturbed blood gas balance is related to reduced diaphragm muscle strength. Mechanical ventilation for only 20 min restores blood gas homeostasis and muscle strength. Therefore, monitoring and maintenance of blood gas balance should be conducted to ensure quality and relevance of small animal experiments.

Corrigendum to "Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury".

[This corrects the article DOI: 10.1155/2017/3715037.].

Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury.

The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.