Hydrogen Sulfide Attenuates Sepsis-Induced Cardiac Dysfunction in Infant Rats by Inhibiting the Expression of Cold-Inducible RNA-Binding Protein.

Abstract

Sepsis-induced cardiac dysfunction is one of the most common complications of sepsis. It is also a major cause of death in pediatric intensive care units. The underlying mechanism of sepsis-induced cardiac dysfunction remains elusive. CIRP is a damage-associated molecular pattern that is upregulated during sepsis. H2S has been shown to play a protective role in sepsis-induced cardiac dysfunction in adult animals. This study aimed to determine whether H2S ameliorates the cardiac function in infant rats by inhibiting CIRP-mediated sepsis-induced cardiac dysfunction. Rat pups aged 17-18 days were subjected to CLP to induce sepsis. Six hours after CLP, hemodynamic results demonstrated that there was a significant decrease in ±dP/dtmax, LVEF and LVFS, indicating cardiac dysfunction. The plasma levels of myocardial injury markers such as CKMB, and CTnI were significantly increased at 6 h after CLP. The inhibition of CIRP with C23 improved the cardiac function of the rats with CLP-induced sepsis, accompanied by a significant decrease in ERS activation. Moreover, treatment with 4-PBA (an inhibitor of ERS) ameliorated myocardial injury and dysfunction, accompanied by a significant decrease in ERS activation. Sodium hydrosulfide, a H2S donor, ameliorated CLP-induced cardiac dysfunction and decreased CIRP levels and ERS. In contrast, the inhibition of endogenous H2S production by propargylglycine (a CSE inhibitor) aggravated CLP-induced cardiac dysfunction and increased CIRP levels. In conclusion, this study demonstrated that H2S exerted cardioprotective effects by inhibiting the CIRP/ERS pathway in infant rats with sepsis. These findings might indicate a novel target in the treatment of sepsis in infants.