Old Donor Heart Preservation by Continuous Perfusion with a Preservation Solution Supplemented with Mesenchymal Stem Cell Conditioned Medium Protects Graft Function from Prolonged Cold Storage Followed by Warm Reperfusion

Objectives: Heart transplantation is the standard treatment in end-stage heart failure. Because of the shortage of donor hearts with increasing numbers of patients waiting for transplantation, transplant programs are using older donors and accepting longer ischemic times. Although 4h has been proven to be a clinically safe ischemic time regarding graft survival rates, current organ preservation solutions do not completely prevent the adverse effects of myocardial ischemia/reperfusion (IR). Previous studies have suggested that mesenchymal stem cell (MSC) administration or the administration of their conditioned medium (MSC CM) protect the heart against IR injury. We assessed the hypothesis that older donor hearts' preservation by a continuous MSC CM would protect the graft in the experimental set up of prolonged cold IR injury during heart transplantation.

Methods: Hearts from 15-month-old Lewis donor rats were explanted and continuously perfused for 5h with oxygenated cold (4°C) cardioplegia, including either Custodiol (control group, n = 8) or Custodiol supplemented serum-free medium (medium group, n = 8) or Custodiol supplemented conditioned medium from MSCs (CM group, n = 8), then they were heterotopically transplanted into young recipients. We evaluated in vivo 1.5h after transplantation posttransplant left-ventricular (LV) graft function and coronary blood flow. Rat MSC of bone marrow were isolated and cultured, and the MSC CM at passage P3 was used. To characterize MSC CM, we performed large antibody arrays.

Results: After transplantation, LV systolic function (dP/dt_max: 1,059 ± 114 vs. 1,052 ± 146 vs. 1,621 ± 263 mm Hg/s), diastolic function (dP/dt_min: −624 ± 45 vs. −636 ± 101 vs. −1,123 ± 205 mm Hg/s, Tau: 56 ± 6 vs. 66 ± 7 vs. 34 ± 4 milliseconds) and coronary blood flow (1.0 ± 0.2 vs. 1.2 ± 0.3 vs. 1.7 ± 0.2 mL/min; control vs. medium vs. CM; p < 0.05 vs. CM group),were significantly improved in the CM group compared with both control and medium groups. Furthermore, the rate pressure product, used to determine the myocardial workload, was significantly increased in the CM group compared with both control and medium groups. Additionally, antibody arrays, containing 90 antibodies, revealed the presence of 37 factors involved in either apoptosis, inflammation, angiogenesis or oxidative stress.

Conclusion: In our experimental design continuous perfusion of old donor hearts with Custodiol supplemented MSC CM protects graft function from prolonged cold ischemia followed by warm reperfusion.

No conflict of interest has been declared by the author(s).