Abstract 2269: Exogenous Sulfide Limits Inflammation in Response to Myocardial Ischemia - Reperfusion Injury
Introduction: Hydrogen sulfide (H2S) is produced endogenously in response to myocardial ischemia and thought to be cardioprotective. The mechanism underlying this protection has yet to be fully elucidated, but may be related to the ability of sulfide to limit inflammation. This study investigates the cardioprotection provided by exogenous H2S, generated as sodium sulfide, and its potential anti-inflammatory mechanism of action.
Methods: The mid-LAD coronary artery in 12 Yorkshire swine was acutely occluded for 60 min, followed by reperfusion for 120 min. Controls (6) received placebo, and treatment animals (6) received sulfide 10 min prior to reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue and TTC staining identified the area at risk (AAR) and infarction. Coronary microvascular reactivity was assessed. Tissue was assayed for myeloperoxidase (MPO) activity and inflammatory cytokines.
Results: Pre-I/R hemodynamics were similar between groups, whereas post-I/R mean arterial pressure (mmHg) was reduced by 28.7±5.0 in controls vs. 6.7±6.2 in treatment animals (p<0.05). +LV dP/dt (mmHg/sec) was reduced by 1325±455 in controls vs. 416±207 in treatment animals (p<0.05). Segmental shortening in the AAR was better in treatment animals. Infarct size (% of AAR) in controls was 41.0±7.8% vs. 21.2±2.5% in the treated group (p<0.05). Tissue levels of IL-6, IL-8, and TNFα (see Table⇓) and MPO activity decreased in the treatment group (0.0025±0.003 vs. control 0.0397±0.016 units/mg protein (p<0.05)). Treated animals demonstrated improved microvascular reactivity.
Conclusions: Sodium sulfide provides significant protection in response to I/R injury, improving myocardial function, reducing infarct size, and improving coronary microvascular reactivity, potentially through its anti-inflammatory properties. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.