Hydrogen sulfide: improved hemodynamics and mitigation of ischemia-reperfusion injury in a large animal model (54.8)

Abstract

Abstract Hemorrhagic shock can lead to ischemia-reperfusion (IR) injury followed by multi-organ failure and death. We tested intravenous Hydrogen sulfide (H2S) in a porcine hemorrhagic shock-resuscitation model evaluating IR injury. Experimental design: Sham (n=3); H2S untreated group (n=5); and H2S treated group (n=14). Animals were splenectomized, induced 35% hemorrhage and ischemia by cross-clamping the supraceliac aorta for 50 minutes. Intravenous fluid and H2S were administered at cross-clamp. Serial hemodynamic measurements and blood plasma analysis were followed for 6 h post-cross clamp release. The mean lactate levels (a measure of injury) were markedly lower in H2S group (7.0±1.6 mmol/L) compared to untreated group (9.3±1.2 mmol/L). Epinephrine requirement was significantly (P<0.05) lower in H2S group (727±645 µg) compared to untreated group (3052±1700 µg). Cardiac output was significantly (P<0.05) lower in H2S treated pigs. The intravenous fluid, hematocrit, and body temperature did not differ significantly (P<0.05). Blood plasma pro-inflammatory cytokines (IL1-β, IL-6, IFN-γ, TNF-α) at 6 h post-cross clamp release were significantly lower (P<0.05) compared to baseline in both H2S treated (n=4) and untreated groups (n=3). Organ (liver, kidney, heart, lung, small bowel, aorta) histopathology and gene expression (iNOS, eNOS, HO-1, HIF-1α, TNFα, IL-6, IFN-γ, IL1-β, etc.,) analyses are in progress. H2S improved hemodynamics and appears to be protective against IR injury.