Abstract
Although essential in critical care medicine, mechanical ventilation often results in ventilator-induced lung injury. Low concentrations of hydrogen sulfide have been proven to have anti-inflammatory and anti-oxidative effects in the lung. The aim of this study was to analyze the kinetic effects of pre- and posttreatment with hydrogen sulfide in order to prevent lung injury as well as inflammatory and oxidative stress upon mechanical ventilation. Mice were either non-ventilated or mechanically ventilated with a tidal volume of 12 ml/kg for 6 h. Pretreated mice inhaled hydrogen sulfide in low dose for 1, 3, or 5 h prior to mechanical ventilation. Posttreated mice were ventilated with air followed by ventilation with hydrogen sulfide in various combinations. In addition, mice were ventilated with air for 10 h, or with air for 5 h and subsequently with hydrogen sulfide for 5 h. Histology, interleukin-1β, neutrophil counts, and reactive oxygen species formation were examined in the lungs. Both pre-and posttreatment with hydrogen sulfide time-dependently reduced or even prevented edema formation, gross histological damage, neutrophil influx and reactive oxygen species production in the lung. These results were also observed in posttreatment, when the experimental time was extended and hydrogen sulfide administration started as late as after 5 h air ventilation. In conclusion, hydrogen sulfide exerts lung protection even when its application is limited to a short or delayed period. The observed lung protection is mediated by inhibition of inflammatory and oxidative signaling.
Highlights
Despite advances in ventilator therapy over the last two decades [1], the risk that mechanical ventilation will induce or aggravate lung injury (i.e., ventilator-induced lung injury (VILI)) remains unacceptably high [2]
With respect to circulatory function, only after 5 h of H2S preconditioning followed by 6 h air ventilation, mean arterial pressure was reduced compared to 6 h air ventilation alone, while mean arterial pressure (MAP) in all other groups did not vary
While mechanical ventilation with air alone led to a significantly augmented VILI score compared to controls and all other treatments, there was a stepwise reduction from 1 and 3 h H2S pretreatment to 5 h H2S pretreatment and 6 h H2S ventilation
Summary
Despite advances in ventilator therapy over the last two decades [1], the risk that mechanical ventilation will induce or aggravate lung injury (i.e., ventilator-induced lung injury (VILI)) remains unacceptably high [2]. This is true for ventilated patients with pre-existing lung disease, but VILI occurs during ventilation of healthy lungs [3,4]. The excessive production of ROS upon mechanical ventilation may per se damage lung tissue by peroxidation of cell lipids, DNA breakage, or alteration of amino acids and cellular metabolism [7,8]. In order to limit both of these responses to mechanical ventilation and reduce lung injury, a treatment option targeted at these mechanisms would be highly desirable
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