Abstract 16872: Continuous Perfusion With a Preservation Solution Supplemented by a Mesenchymal Stem Cell Conditioned Medium Protects the Older Hearts From Prolonged Cold Storage Followed by Warm Reperfusion
Introduction: Heart transplantation is the first choice of therapy for end-stage heart failure patients. 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 preservation solutions ensure a safe cold ischemic time of 4h, they do not completely prevent the adverse effects of myocardial ischemia/reperfusion (IR) injury. Previous studies have suggested beneficial effects of mesenchymal stem cell (MSC) administration or the administration of their conditioned medium (MSC CM) in animal models of IR injury.
Hypothesis: Older donor hearts’ preservation by a continuous conditioned medium from MSC (MSC CM) was investigated in the experimental set up of prolonged cold IR injury during heart transplantation.
Methods: The hearts were explanted from 15-month-old Lewis donor rats 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, old donor hearts were heterotopically transplanted into young recipients. We evaluated in vivo left ventricular (LV) graft function and coronary blood flow 1.5h after transplantation. Rat MSC of bone marrow were isolated and cultured. The MSC CM at passage P3 was used and characterized by antibody arrays (90 proteins).
Results: After transplantation, coronary blood flow (1.0±0.2 vs. 1.2±0.3 vs. 1.7±0.2 ml/min), LV systolic function (dP/dtmax: 1059±114 vs. 1052±146 vs. 1621±263 mmHg/s) and diastolic function (dP/dtmin: -624±45 vs. -636±101 vs. -1123±205 mmHg/s, Tau: 56±6 vs. 66±7 vs. 34±4 ms; control group vs. medium group vs. CM group; p<0.05 vs. CM group) were significantly improved in CM group compared to both control and medium groups. Furthermore, antibody arrays revealed the presence of 37 factors involved in either apoptosis, inflammation, angiogenesis or oxidative stress.
Conclusions: Continuous perfusion with the organ preservation solution, Custodiol supplemented MSC CM, protects the older hearts from prolonged cold ischemia followed by warm reperfusion.
Author Disclosures: S. Li: Research Grant; Significant; Ernst und Berta Grimmke – Stiftung. S. Korkmaz-Icöz: Research Grant; Significant; Ernst und Berta Grimmke – Stiftung. M. Ruppert: None. T. Radovits: None. K. Li: None. X. Sun: None. P. Brlecic: None. M. Karck: None. G. Szabó: Research Grant; Significant; Ernst und Berta Grimmke – Stiftung.
- © 2016 by American Heart Association, Inc.