Nitric Oxide 2018 12 11;81:1-10. Epub 2018 Sep 11.
Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, China. Electronic address:
Cardiac transplantation has been limited by the inability to long preserve donor hearts safely. Hydrogen sulfide (HS) has been recognized as an important gasotransmitter exerting potent cardioprotection from ischemia/reperfusion injury (I/R). Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing HS system, namely DATS-MSN, in heart preservation solution using a heart transplantation models. The release of HS from DATS-MSN was slow and continuous in the University of Wisconsin solution (UW), correspondingly, DATS-MSN application demonstrated superior cardioprotective effects over the control and traditional HS donors after 6 h heart preservation and 1 h reperfusion, associated with greater allograft performance including left ventricular developed pressure (LVDP) and dP/dt , reduced plasmic CK-MB and troponin I levels, inhibited myocardial inflammation, increased antioxidant enzyme activities, preserved mitochondria structure and function, and decreased cardiomyocyte apoptosis index. Also, DATS-MSN application presented significant superiority in long-term allografts survival and function after 8 weeks of transplantation. In the in vitro experiments, cardiomyocytes injury from hypoxia was found to be relived with the treatment of DATS-MSN by anti-inflammatory effects via TLR4/NLRP3 pathway. The present work provides a long-term releasing HS donor compatibly applied in the donor heart preservation, and preliminary explores its underlying mechanisms.