Abstract 16163: Hydrogen Sulfide Reduces Inflammasome Formation in Mice With Ischemic HFrEF
Background: Hydrogen sulfide (H2S) has been shown to attenuate myocardial ischemia/reperfusion injury via suppression of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Whether the H2S donor, Na2S, protects against ischemic heart failure with reduced ejection fraction (HFrEF) when treatment is initiated after development of LV dysfunction is unknown.
Methods and Results: Adult male mice underwent myocardial infarction (MI) by permanent coronary artery ligation after baseline echocardiography. Repeat echocardiography was performed at day 3 post MI and surviving mice with fractional shortening (FS) less than 25% were treated with either Na2S (100 μg/kg, ip) or saline (volume matched, ip) for 25 days. LV fractional shortening remained unchanged at 7 and 28 days post-MI in the saline group, but improved significantly with Na2S at both time points (Fig. A). Moreover, LV infarct scar size, assessed by trichrome staining, was smaller in Na2S group (14.8 ± 2.1%) as compared to control (28.8 ± 4.8%, P<0.05) at 7 days post MI. Immunofluorescence staining for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), a component of the inflammasome, showed significant increase at 3 days post MI with sustained elevation at 7 days in the saline-treated group, whereas treatment with Na2S starting on day 3 post-MI significantly attenuated ASC 4 days later (Fig. B). Survival rate was 2-fold higher in Na2S group compared to saline control at 28 days post MI (P<0.05, Fig. C).
Conclusion: Treatment with Na2S in mice with ischemic HFrEF improves LV function and survival up to 28 days post MI, possibly through suppression of ASC and prevention of further NLRP3 inflammasome formation. We propose that H2S donors can be promising therapeutic tools for ischemic HF.
Author Disclosures: A.G. Mauro: None. J. Valle Raleigh: None. K. Nguyen: None. D.E. Durrant: None. E. Kim: None. P. Pottanat: None. J. He: None. S. Toldo: None. A. Abbate: None. F.N. Salloum: None.
- © 2015 by American Heart Association, Inc.