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

Abstract

Cardiac transplantation has been limited by the inability to long preserve donor hearts safely. Hydrogen sulfide (H2S) 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 H2S system, namely DATS-MSN, in heart preservation solution using a heart transplantation models. The release of H2S 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 H2S 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 H2S donor compatibly applied in the donor heart preservation, and preliminary explores its underlying mechanisms.