Apoptotic Markers in Donor Hearts After Brain Death vs Circulatory Death

Use of donation after circulatory death (DCD) hearts is becoming more prevalent in cardiac transplantation. However, there is no standardized approach to myocardial preservation, and little data exists on ultrastructural changes in DCD hearts. We have previously identified increased proapoptotic and proinflammatory activity in brain dead donor (BDD) hearts that subsequently exhibit primary graft failure and lower levels in DCD left atrial tissue. This study further investigates these markers and correlates them with cardiac function in DCD hearts.

This prospective study used donor hearts deemed unsuitable for transplant after gaining institutional ethics approval; 11 human hearts were obtained from 5 DCD donors and 6 BDDs. All hearts were preserved by continuous microperfusion for 4 hours with a cold crystalloid solution and then were evaluated on a blood perfusion bench rig. After 4 hours perfusion and working assessment, tissues from all cardiac chambers were stored for later messenger RNA (mRNA) analysis for proapoptotic and proinflammatory markers.

Significantly raised levels of caspase-1, BNIP3, and NADPH oxidase mRNA expression were identified in cardiac chambers from BDD hearts compared to DCD hearts, and these differences were exaggerated in older donors. In the pooled analysis, lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with developed pressure at 1 hour after reperfusion in the right ventricle, but not the left.

Compared to BDD hearts, DCD hearts exhibit less stimulation of proapoptotic cascades and reactive oxygen species, potentially reducing their susceptibility to ischemic reperfusion injury.