Evaluation of Graft Function in Which Donor Hearts Were Retrieved under Exsanguination- or Apnea-Induced Non–Heart-Beating Conditions

Objectives: The use of marginal hearts, such as from non-heart-beating donors (NHBDs) could offer the opportunity to increase the provision of the organs available for transplantation. Preclinical studies showed that hearts from NHBDs recovered function similar to that from brain-dead donor. There are several experimental methods of simulating NHBDs conditions to study the effects of NHBDs on organ quality such as exsanguination and hypoxic cardiac arrest both followed by warm ischemia. We compared two non-heart-beating models in rat heart transplantation in which grafts were retrieved under exsanguination- or apnea-induced non–heart-beating conditions.

Methods: Donor hearts were either maintained in situ for 10min after cardiac arrest, which was induced by rapid exsanguination (exsanguination group, n = 6) or subjected to hypoxic cardiac arrest followed by 10min of warm ischemia (asphyxia group, n = 6). Additionally, a control group (n = 6), in which heart grafts were retrieved from heart beating donors, was used. Then, hearts were perfused with a cold preservation solution (Custodiol), explanted, stored at 4°C in Custodiol for 1h and heterotopically transplanted. We evaluated graft damage 1.5 hours after transplantation.

Results: After transplantation, significantly decreased systolic function (left-ventricular systolic pressure: exsanguination 64 ± 6 mm Hg versus asphyxia 47 ± 6 mm Hg versus control 89 ± 5 mm Hg; dP/dt_max: exsanguination 1,700 ± 85 mm Hg/s versus asphyxia 2,313 ± 262 mm Hg/s versus control 3,333 ± 147 mm Hg/s, p < 0.05) and diastolic function were observed in both exsanguination and asphyxia groups compared with controls. Additionally, asphyxia group showed further impaired diastolic function when compared with the exsanguination group (dP/dt_min: asphyxia 1,044 ± 81 mm Hg/s versus exsanguination 1588 ± 160 mm Hg/s, p < 0.05). Histological analysis revealed mild edema, mild local inflammatory cell infiltration, and rare necrosis in all experimental groups. However, cardiac arrest by exsanguination or asphyxia did not induce additional histological damage. Western blot showed that protein levels of caspase-3, tumor necrosis factor α, cyclooxygenase-2, nuclear factor KappaB, inducible nitric oxide synthase, cytochrome-c and SERCA-2 did not differ between the groups.

Discussion: Our results showed that both models appear to be useful for investigating new strategies to assess and optimize the graft function in NHBDs heart transplantation.