Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

Abstract

Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1‐year outcomes

“…Cold storage disrupts cellular homeostasis and leads to ATP depletion, fluid stasis, edema, and reperfusion injury. Prolonged time in a nonhomeostatic environment exacerbates damage and risks tissue viability 4,10,11 . Compared to other solid organ transplants, the heart is especially sensitive to the effects of cold ischemic storage 4,10,11 .…”

Neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as predictors of survival after heart transplantation

“…31 Several inflammatory pathways are activated both before and after HTX, including infiltrating cells like neutrophils and lymphocytes, inflammatory cytokines like IL-1 and IL-18, the NLRP3 inflammasome, and toll-like receptor activation. 31,32 Experimental studies have shown that modulating the innate inflammatory response is associated with improved survival after HTX, yet there is no specific approved treatment in this direction. Our study confirms the association between increase innate inflammation and worse outcome in HTX and strengthens the need for specific treatments.…”

Wearable and Implantable Devices for Cardiovascular Healthcare: from Monitoring to Therapy Based on Flexible and Stretchable Electronics

“…To restore the intrinsic function of cardiac tissue, heart transplantation has been the only option . As mentioned earlier, heart transplantation is limited owing to the low availability of heart donors and the high risk of immune response . Hence, cell‐based therapies have gained attention for their capability to treat damaged cardiac tissue .…”