title: Suspended animation inducer hydrogen sulfide is protective in an in vivo model of ventilator-induced lung injury.
abstract: OBJECTIVE
  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.
authors: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center, Amsterdam, The Netherlands.
authors: Hamid
authors: H
authors: Aslami
authors: André
authors: A
authors: Heinen
authors: Joris J T H
authors: JJ
authors: Roelofs
authors: Coert J
authors: CJ
authors: Zuurbier
authors: Marcus J
authors: MJ
authors: Schultz
authors: Nicole P
authors: NP
authors: Juffermans
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008991:Monitoring, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
chemical_list: D006862:Hydrogen Sulfide