S. Satterly1, J. Stallings1, S. Salgar1, Z. Hoffer1, M. Martin1 1Madigan Army Medical Center,Surgery,Tacoma, WA, USA
Introduction: Hydrogen sulfide (H2S) has been demonstrated to induce a “suspended animation-like” state in rodent models by reversible inhibition of cellular respiration and marked metabolic suppression, and has been proposed as a potential pharmacologic adjunct to resuscitation from shock states. There is little data currently available about the mechanisms and efficacy of H2S in larger animals or humans. We examined H2S as a pharmacologic adjunct to resuscitation in a porcine model of severe traumatic shock.
Methods: Twenty-one adult swine were assigned to 3 study arms: sham, H2S, and saline vehicle controls (SC). All pigs underwent laparotomy and instrumentation, and the 2 study arms then underwent a 35% controlled hemorrhage followed by 50 minutes of truncal ischemia via aortic cross-clamp. H2S (5mg/kg) or saline was administered immediately prior to reperfusion, followed by 6 hours of resuscitation. Resuscitation requirements, laboratory parameters, end-organ histology, and inflammatory/oxidative product gene expression (by rtPCR) were measured and compared between groups.
Results: All animals survived to the 6-hour post resuscitation time point. Both treatment arms demonstrated severe shock characterized by fluid and vasopressor requirements, metabolic acidosis, and hypotension compared to sham animals. Animals treated with H2S demonstrated significantly lower resuscitative requirements (total epinephrine 727 µg vs 3052 µg, p<0.05), decreased fluid requirements, and lower serum lactate levels (7 mmol/L vs 10 mmol/L) versus SC. Cardiac output was slightly decreased with H2S treatment but all other hemodynamic and metabolic parameters were equivalent between H2S and C groups. Serum liver and kidney biomarkers were unchanged, but administration of H2S was associated with a significant improvement in histopathologic liver and kidney injury scores compared to SC (see Figure, both p<0.05). Both study groups demonstrated significantly increased gene expression of hypoxia inducible factor (HIF-1α), and nitric oxide synthase (eNOS, iNOS2, iNOS3) relative to sham animals. However, H2S was associated with increased expression of HIF-1α and decreased iNOS2 levels compared to SC.
Conclusion: Administration of H2S in a large animal model of severe traumatic shock resulted in a significant decrease in resuscitative requirements, decreased metabolic acidosis, and less end-organ histologic injury compared to standard resuscitation. H2S did not induce profound metabolic suppression as seen in rodents, and appears to have alternative mechanisms of action in large animals.
