Donor Heart Recovery and Preservation Modalities in 2024.

Historically, heart transplantation (HT) has relied on the use of traditional cold storage for donor heart preservation. This organ preservation modality has several limitations, including the risk for ischemic and cold-induced graft injuries that may contribute to primary graft dysfunction and poor post-HT outcomes. In recent years, several novel donor heart preservation modalities have entered clinical practice, including the SherpaPak Cardiac Transport System of controlled hypothermic preservation, and the Transmedics Organ Care System of ex vivo perfusion. Such technologies are altering the landscape of HT by expanding the geographic reach of procurement teams and enabling both donation after cardiac death and the use of expanded criteria donor hearts. This paper will review the emerging evidence on the association of these modalities with improved post-HT outcomes, and will also suggest best practices for selecting between donor heart preservation techniques.

Research status of machine perfusion of heart / 器官移植

High-quality donor heart is the prerequisite and fundamental guarantee for successful heart transplantation. Reasonable donor heart preservation technique plays a key role in improving the quality of donor heart and the prognosis of heart transplantation. Static cold storage (SCS) is currently the standard preservation technique for cardiac allograft. However, it is prone to cause severe cold ischemia injury to the donor heart, and it is impossible to evaluate heart function during SCS. As an important emerging technique of organ preservation, machine perfusion better matches with physiological conditions compared with SCS, which may remove metabolic wastes and provide basic substances for metabolic needs during organ preservation, prolong the preservation time and improve the preservation effect to a certain extent. Besides, it may also effectively evaluate organ function and improve clinical prognosis of heart transplantation. Meantime, it can also repair organ damage, significantly optimize organ quality and improve the utilization rate of donor organs. In this article, research status of machine perfusion of donor heart was reviewed.

Bone marrow- or adipose-mesenchymal stromal cell secretome preserves myocardial transcriptome profile and ameliorates cardiac damage following ex vivo cold storage.

BACKGROUND: Heart transplantation, a life-saving approach for patients with end-stage heart disease, is limited by shortage of donor organs. While prolonged storage provides more organs, it increases the extent of ischemia. Therefore, we seek to understand molecular mechanisms underlying pathophysiological changes of donor hearts during prolonged storage. Additionally, considering mesenchymal stromal cell (MSC)-derived paracrine protection, we aim to test if MSC secretome preserves myocardial transcriptome profile and whether MSC secretome from a certain source provides the optimal protection in donor hearts during cold storage. METHODS AND RESULTS: Isolated mouse hearts were divided into: no cold storage (control), 6 h cold storage (6 h-I), 6 h-I + conditioned media from bone marrow MSCs (BM-MSC CM), and 6 h-I + adipose-MSC CM (Ad-MSC CM). Deep RNA sequencing analysis revealed that compared to control, 6 h-I led to 266 differentially expressed genes, many of which were implicated in modulating mitochondrial performance, oxidative stress response, myocardial function, and apoptosis. BM-MSC CM and Ad-MSC CM restored these gene expression towards control. They also improved 6 h-I-induced myocardial functional depression, reduced inflammatory cytokine production, decreased apoptosis, and reduced myocardial H2O2. However, neither MSC-exosomes nor exosome-depleted CM recapitulated MSC CM-ameliorated apoptosis and CM-improved mitochondrial preservation during cold ischemia. Knockdown of Per2 by specific siRNA abolished MSC CM-mediated these protective effects in cardiomyocytes following 6 h cold storage. CONCLUSIONS: Our results demonstrated that using MSC secretome (BM-MSCs and Ad-MSCs) during prolonged cold storage confers preservation of the normal transcriptional "fingerprint", and reduces donor heart damage. MSC-released soluble factors and exosomes may synergistically act for donor heart protection.

Utilization of Paragonix SherpaPak for human donor heart preservation.

A heart transplant is the gold standard treatment for end stage heart failure. Preservation of the donor heart during its transfer from the hospital of the donor to that of the recipient has a significant impact on the outcome of the transplant procedure. Icebox storage is a conventional method utilized for this purpose that may not provide uniform cooling of the donor heart and does not allow monitoring of the temperature of the donor heart during preservation. The Paragonix SherpaPak Cardiac Transport System offers uniform cooling by suspending the donor heart in a preservation solution and provides continuous temperature monitoring.

Ex situ heart perfusion: The past, the present, and the future.

Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening. Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability. This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation.

Myocardial protection with complementary dose of modified Del Nido cardioplegia during heart transplantation.

Myocardial protection during heart transplantation is achieved by a first dose of heart preservation solution during donor heart harvesting, while there is no consensus about the management of complementary doses during implantation in the recipient. We describe a preliminary case series where modified Del Nido Cardioplegia was used as complementary dose at the time of donor heart implantation.

Preservation of the donor heart: from basic science to clinical studies.

The methods of donor heart preservation are aimed at minimizing graft dysfunction caused by ischaemia-reperfusion injury (IRI) which inevitably occurs during the ex vivo transport interval. At present, the standard technique of heart preservation is cardiac arrest followed by static cold storage in a crystalloid heart preservation solution (HPS). This technique ensures an acceptable level of heart protection against IRI for <6 h. In clinical trials, comparable levels of myocardial protection against IRI were provided by various HPSs. The growing shortage of donor hearts is one of the major factors stimulating the development of new techniques of heart preservation. Here, we summarize new HPS formulations and provide a focus for optimization of the composition of existing HPSs. Such methods of donor heart preservation as machine perfusion, preservation at sub-zero temperature and oxygen persufflation are also discussed. Furthermore, we review experimental data showing that pre- and post-conditioning of the cardiac graft can improve its function when used in combination with cold storage. The evidence on the feasibility of cardiac donation after circulatory death, as well as the techniques of heart reconditioning after a period of warm ischaemia, is presented. The implementation of new techniques of donor heart preservation may contribute to the use of hearts from extended criteria donors, thereby expanding the total donor pool.

Experimental study on fasudil for increasing preserving effect on porcine DCD heart induced by ischemia / 重庆医学

Objective To evaluate the effects of fasudil on DCD hearts .Methods Sixteen domestic ,mixed‐breed male porcine [mean body weight (28 ± 3)kg] were randomly divide into experiment group and control group (n= 8 in each) .Experiment group :animals were sedated ,anesthetized and paralyzed .Mechanical ventilation with room air was provided .After thoroctomy ,cardiac arrest was established by bloodletting ,and then keeps at room temperature for additional 25 minutes (warm ischemia) .Hearts were perfused via the aortic root with fasudil (0 .1 mg/kg) enriched cold Stanford solution for coronary artery flushing ,rapidly excised and the aorta was cannulated .Hearts were subjected to isolated Langendorff perfusion (retrograde perfused with warm oxygenated autologous blood) afterwards ,and then underwent 20 minutes of equilibrium ,immersed in fasudil (0 .5 mg/kg) enriched cold Stan‐ford solution for 2 hours in situ cold preservation .Finally ,all the hearts were resuscitated with the warm oxygenated autologous blood perfusion .Control group :hearts from the animals experienced the same except for fasudil supplement .Left ventricular per‐formances were evaluated .Coronary blood flow ,myocardial infarction volume ,myocardial water content ,and myocardial enzyme were measured .Myocardial electron microscopic examinations were carried out as well .Results All the hearts from both groups were successfully resuscitated ,fasudil significantly decreased water content ,enzyme leakage (P< 0 .01 each versus control group) , and increased coronary blood flow (P< 0 .01 versus control group) .Left ventricular function were better preserved (P< 0 .01 each versus control group) .All hearts lacked severe necrosis as determined by tetrazolium staining ,myocardial infarction volume were decresed in experiment group (P< 0 .01 each versus control group) .Intracellular components retained various types of organelle in both group ,but still ultrastructural alterations in control group were more distinctive than in experiment group .Conclusion (1) Donor heart arrested by exsanguinations and plus 25 minutes warm ischemia ,could still be resuscitated with satisfactory result ;(2) The addition of fasudil to Stanford solution (before excise of graft ,during the cold preservation) ,might alleviate DCD heart I‐R in‐jury ,improving the effect of DCD heart preservation ,and hopefully ,might be a novel arsenal in clinical DCD heart transplantation in the future .