Suspended animation inducer hydrogen sulfide is protective in an in vivo model of ventilator-induced lung injury

PURPOSE: Acute lung injury is characterized by an exaggerated inflammatory response and a high metabolic demand. Mechanical ventilation can contribute to lung injury, resulting in ventilator-induced lung injury (VILI). A suspended-animation-like state induced by hydrogen sulfide (H₂S) protects against hypoxia-induced organ injury. We hypothesized that suspended animation is protective in VILI by reducing metabolism and thereby CO₂ production, allowing for a lower respiratory rate while maintaining adequate gas exchange. Alternatively, H₂S may reduce inflammation in VILI. METHODS: In mechanically ventilated rats, VILI was created by application of 25 cmH₂O positive inspiratory pressure (PIP) and zero positive end-expiratory pressure (PEEP). Controls were lung-protective mechanically ventilated (13 cmH₂O PIP, 5 cmH₂O PEEP). H(2)S donor NaHS was infused continuously; controls received saline. In separate control groups, hypothermia was induced to reproduce the H₂S-induced fall in temperature. In VILI groups, respiratory rate was adjusted to maintain normo-pH. RESULTS: NaHS dose-dependently and reversibly reduced body temperature, heart rate, and exhaled amount of CO₂. In VILI, NaHS reduced markers of pulmonary inflammation and improved oxygenation, an effect which was not observed after induction of deep hypothermia that paralleled the NaHS-induced fall in temperature. Both NaHS and hypothermia allowed for lower respiratory rates while maintaining gas exchange. CONCLUSIONS: NaHS reversibly induced a hypometabolic state in anesthetized rats and protected from VILI by reducing pulmonary inflammation, an effect that was in part independent of body temperature.