Donor heart preservation with a novel long-term and slow-releasing hydrogen sulfide system

摘要

Cardiac transplantation has been limited by the inability to long preserve donor hearts safely. Hydrogen sulfide (H_2S) 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 slowreleasing H_2S system, namely DATS-MSN, in heart preservation solution using a heart transplantation models. The release of H_2S 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 H_2S donors after 6 h heart preservation and 1 h reperfusion, associated with greater allograft performance including left ventricular developed pressure (LVDP) and dP/dt max, 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 H_2S donor compatibly applied in the donor heart preservation, and preliminary explores its underlying mechanisms.