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Due to the discrepancy between patients awaiting a heart transplant and the availability of donor hearts, strategies to expand the donor pool and improve the transplant's success are crucial. This review aims to summarize current knowledge on the ex vivo heart preservation (EVHP) experience as an alternative to standard cold static storage (CSS). EVHP techniques can improve the preservation of the donor's heart before transplantation and allow for pre-transplant organ evaluation. [ABSTRACT FROM AUTHOR]

Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6–55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Objective: to evaluate the technical feasibility as well as functional, metabolic and structural integrity of donor heart myocardium after 4 hours of direct intracoronary oxygen persufflation in an experiment. Materials and methods. Mini-pig siblings aged 3 months with a body weight of 23–36 kg were used as the experimental model. In the control group (n = 8), donor hearts were cold preserved by injecting 2 liters of Bretschneider cardioplegic solution (Custodiol®, Germany, HTK) into the aortic root. In the experimental group (n = 8), modified HTK solution (with 40 mg/L hyaluronidase added) was used to initiate cardioplegia, then moistened carbogen (95% O2, 5% CO2) was injected into the ascending aorta, maintaining 40–45 mm Hg aortic root pressure. The hearts were stored in an mHTK solution at 0–4 °С. After 3 hours of donor heart preservation, orthotopic heart transplantation (OHTx) was performed. In the post-transplant period, we studied central hemodynamic parameters, myocardial oxygen consumption, level of myocardial ischemia markers (troponin I, TnI; creatine phosphokinase-MB, CPKMB; lactate dehydrogenase, LDH), and histological signs of structural cellular injury. Results. Sixteen OHTx surgeries were performed during the study. At 120 minutes after restoration of spontaneous cardiac activity, cardiac output was 2.99 [4.85; 3.17] L/min and 2.48 [2.04; 2.92] L/min (p > 0.05) in the control and experimental groups, respectively. Changes in LDH, TnI and lactate levels in the blood flowing from the coronary sinus were significantly higher in the early reperfusion period. However, there was no statistically significant difference between the groups (p > 0.05). Myocardial oxygen consumption in the control and experimental groups was 8.2 [7.35; 9.35] ml-O2/min/100 g and 7.7 [6.75; 10.12] ml-O2/min/100 g, respectively (p > 0.05). Morphological examinations also showed no significant myocardial ischemia injury in the persufflation group compared to the control group. Conclusion. The experiment showed the technical feasibility and safety of direct intracoronary oxygen persufflation for 4 hours at the ex vivo donor heart conditioning stage. At the same time, experimental data showed no significant advantages of coronary persufflation over the standard protocol of cold preservation of donor heart with Bretschneider cardioplegic solution.

BackgroundHydrogen sulfide (H2S) is known for its unpleasant odor and severe toxicity. However, an in-depth study of H2S showed that it can be used as an important messenger, which can play important physiological and pathological roles in vitro and in vivo. In recent years, the application of H2S in the field of cardiac preservation has attracted the interest and attention of scholars worldwide. H2S plays an effective and protective role in cardiac ischemia/reperfusion injury through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.ObjectiveThe purpose of this study is to analyze the current scientific achievements on the application of H2S in the field of cardiac preservation and to provide new ideas for further research.MethodsTS = (“hydrogen sulfide” OR “hydrogen sulfide”) AND TS = (“cardiac” OR “heart” OR “myocardium” OR “hearts”) AND TS = (“reperfusion” or “transplantation” or “implanted” or “transplant” or “implantation” or “migration” or “preservation” or “grafting” OR “ischemia” OR “perfusion” or “conservation” or “preserve” or “reservation”) AND DT = (Article OR Review) AND LA = (English) were used as search strategies for data collection from the Science Citation Index-Expanded database of the Web of Science Core Collection. CiteSpace 5.8. R3 and Microsoft Office Excel 2019 were used for data analysis.ResultsA total of 429 related articles were included, and the total number of articles showed a fluctuating upward trend. We used CiteSpace 5.8. R3 and Microsoft Excel 2019 to evaluate and visualize the results, analyzing institutions, countries, journals, authors, co-cited references, and keywords.ConclusionsAs increasing evidence shows that H2S plays an indispensable role in the field of cardiac preservation, its mechanistic research and clinical application may become the main focus of future research.

Heart transplantation has become the accepted treatment for advanced heart failure, with over 4000–5000 performed in the world annually. Although the number of yearly transplants performed has been increasing over the last decade, the number of candidates in need of transplantation continues to grow at an even faster rate. To distribute these scarce and precious resources equitably, donor heart placement is based on clinical need with priority given to those who are more critically ill. As a result, donors are matched with recipient candidates over increasingly farther distances, which may subject these organs to longer ischemic times. One of the mainstays of successful heart transplantation is successful organ preservation while the donor organ is ex vivo from the time of donor procurement to recipient implantation. In order to adapt to a new era of heart transplantation where organs are shared across wider ranges, preservation strategies must evolve to accommodate longer ischemia times while mitigating the harmful sequalae of ischemia-reperfusion injury. Additionally, in order to address the ever-growing supply demand mismatch of donor organs, evolving perfusion technologies may allow for further evaluation of donor grafts outside of conventional acceptance practices, thus enlarging the effective donor pool. Herein this review, we discuss the history of organ preservation, current strategies and modalities employed in current practice, along with developing technologies in preclinical stages. Lastly, we introduce the concept of donation after circulatory death (DCD), which has been until recently a largely unexplored avenue of heart donation that relies much on current preservation techniques. [ABSTRACT FROM AUTHOR]

Background: Donation after circulatory death (DCD) hearts requires machine perfusion preservation, the conditions of which are not well defined. Methods: To achieve this, rat hearts were procured following a DCD or control beating‐heart donation (CBD) model, and perfused for 60 min with one of three machine perfusion solutions—St. Thomas (ST), University of Wisconsin (UW), or Polyethylene Glycol‐20k (PEG)—at one of two temperatures, 4°C or 15°C. At 15‐min intervals, perfusion pressure was measured as a marker of vascular resistance. Colored microspheres were added to capture the distribution of perfusate into the metabolically active sub‐endocardium, and the eluate was collected for troponin assays. Analyses compared groups using Wilcoxon rank‐sum and ANOVA. Results: Perfusion pressure was significantly higher for DCD than CBD hearts at 15°C regardless of solutions. The lowest rise in perfusion pressure over time was observed with PEG at 15°C. Except for PEG at 15°C, ST and UW solutions at 4 or 15°C had decreased sub‐endocardial perfusion in DCD hearts. Troponin release from DCD hearts with UW and PEG solutions was comparable to CBD hearts but was significantly higher with ST solution at 15°C. Conclusions: Optimal preservation conditions for DCD hearts were observed with PEG machine perfusion solution at 15°C. [ABSTRACT FROM AUTHOR]

Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard clinically. However, machine perfusion (MP) is considered an approach for donor organ management to extend the donor pool and/or increase the utilization rate. This review summarizes and critically assesses the available clinical data on MP in heart transplantation. We searched Medline (PubMed), Cochrane, Embase, and clinicaltrials. gov, along with reference lists of the included publications and identified 40 publications, including 18 articles, 17 conference abstracts, and five ongoing clinical trials. Two types of MP were used: hypothermic MP (HMP) and normothermic MP (NMP). Three studies evaluated HMP, and 32 evaluated NMP. Independent of the system, MP resulted in clinical outcomes comparable to traditional SCS. However, NMP seemed especially beneficial for high-risk cases and donation after circulatory death (DCD) hearts. Based on currently available data, MP is non-inferior to standard SCS. Additionally, single-centre studies suggest that NMP could preserve the hearts from donors outside standard acceptability criteria and DCD hearts with comparable results to SCS. Finally, HMP is theoretically safer and simpler to use than NMP. If a machine malfunction or user error occurs, NMP, which perfuses a beating heart, would have a narrower margin of safety. However, further welldesigned studies need to be conducted to draw clear conclusions. [ABSTRACT FROM AUTHOR]

The advantages of oxygenated perfusion are continuing to be demonstrated by many groups focused on improving the efficacy of tissue preservation for transplant, bioreactors for studies of basic tissue physiology, and closed-loop resuscitation. This work presents a novel and portable device that supplies oxygenated and pulsatile perfusion, both of which are regulated by a single pump-oxygenator component comprised of silicone tubes that are cyclically inflated/deflated with compressed oxygen. In this study, pump variables (oxygen supply pressure and length of a silicone tube) were evaluated against hydraulic elements that mimicked the vascular resistance of kidneys, livers, and hearts. The perfusion pressures, flow rates, and oxygenation rates produced by the device were characterized for all configurations of pump variables, and the pulse rates were tuned to improve performance. The device supplied perfusion pressures ranging from 3.5 to 109 mmHg, flow rates ranging from 1.4 to 71.8 mL min−1, and oxygenation rates up to 316.6 µmol min−1. From those results, it was determined that the device was capable of achieving perfusion parameters used in previous kidney, liver, and heart preservation studies. Ultimately, this research demonstrated the efficacy of a novel device that is designed to supply oxygenated perfusion across a range of applications. [ABSTRACT FROM AUTHOR]

Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts ( n  = 42) of different sizes (6-55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions ( n  = 15); (2) NEHP + plasma exchange ( n  = 5); (3) NEHP + hemofiltration ( n  = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration ( n  = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion ( n  = 7). All hearts with NEHP + interventions ( n  = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group ( n  = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Spencer, Wilhelm, Stephan, Urrea, Palacio, Bartlett, Drake and Rojas-Pena.)

ObjectiveThe adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD.MethodsDonor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 μmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated.ResultsTwenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dtmax, and dP/dtmin of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dtmax of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group.ConclusionEVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.

Background: In heart transplantation, the adoption of hearts from donation after circulatory death (DCD) is considered to be a promising approach to expanding the donor pool. Normothermic ex situ heart perfusion (ESHP) is emerging as a novel preservation strategy for DCD hearts. Therefore, pre-clinical animal models of ESHP are essential to address some key issues before efficient clinical translation. We aim to develop a novel, reproducible, and economical rat model of DCD protocol combined with normothermic ESHP.Methods: Circulatory death of the anesthetized rats in the DCD group was declared when systolic blood pressure below 30 mmHg or asystole was observed after asphyxiation. Additional 15 min of standoff period was allowed to elapse. After perfusion of cold cardioplegia, the DCD hearts were excised and perfused with allogenic blood-based perfusate at constant flow for 90 min in the normothermic ESHP system. Functional assessment and blood gas analysis were performed every 30 min during ESHP. The alteration of DCD hearts submitted to different durations of ESHP (30, 60, and 90 min) in oxidative stress, apoptosis, tissue energy state, inflammatory response, histopathology, cell swelling, and myocardial infarction during ESHP was evaluated. Rats in the non-DCD group were treated similarly but not exposed to warm ischemia and preserved by the normothermic ESHP system for 90 min.Results: The DCD hearts showed compromised function at the beginning of ESHP and recovered over time, while non-DCD hearts presented better cardiac function during ESHP. The alteration of DCD hearts in oxidative stress, apoptosis, tissue energy state, histopathological changes, cell swelling, and inflammatory response didn't differ among different durations of ESHP. At the end of 90-min ESHP, DCD, and non-DCD hearts presented similarly in apoptosis, oxidative stress, inflammatory response, myocardial infarction, and histopathological changes. Moreover, the DCD hearts had lower energy storage and more evident cell swelling compared to the non-DCD hearts.Conclusion: We established a reproducible, clinically relevant, and economical rat model of DCD protocol combined with normothermic ESHP, where the DCD hearts can maintain a stable state during 90-min ESHP.

Heart transplantation has become the accepted treatment for advanced heart failure, with over 4000–5000 performed in the world annually. Although the number of yearly transplants performed has been increasing over the last decade, the number of candidates in need of transplantation continues to grow at an even faster rate. To distribute these scarce and precious resources equitably, donor heart placement is based on clinical need with priority given to those who are more critically ill. As a result, donors are matched with recipient candidates over increasingly farther distances, which may subject these organs to longer ischemic times. One of the mainstays of successful heart transplantation is successful organ preservation while the donor organ is ex vivo from the time of donor procurement to recipient implantation. In order to adapt to a new era of heart transplantation where organs are shared across wider ranges, preservation strategies must evolve to accommodate longer ischemia times while mitigating the harmful sequalae of ischemia-reperfusion injury. Additionally, in order to address the ever-growing supply demand mismatch of donor organs, evolving perfusion technologies may allow for further evaluation of donor grafts outside of conventional acceptance practices, thus enlarging the effective donor pool. Herein this review, we discuss the history of organ preservation, current strategies and modalities employed in current practice, along with developing technologies in preclinical stages. Lastly, we introduce the concept of donation after circulatory death (DCD), which has been until recently a largely unexplored avenue of heart donation that relies much on current preservation techniques.

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.1 Paragonix SherpaPak Cardiac Transport System (CTS), one of the leading FDA-cleared and CE-marked preservation devices for heart transportation, offers a sterile, controlled environment that is clinically proven to minimize post-transplant complications. In our region University Hospital Centre Zagreb has used it for transport of the heart eight times so far. With this CTS we suspended the donor heart in a preservation solution for even cooling in a pressure-controlled, leak-proof, single-use, rigid canister, that provides a consistent temperature range, prevents cold injury, and offers real-time monitoring and data reporting. SherpaPak was recently introduced into our human heart transplant procedure, so the experience is minimal, but so far we are very satisfied, due to uniform hypothermia, continuous monitoring, and single use transport containers. If we compare short term post-transplant outcomes, and utilized data collected by the GUARDIAN-Heart Registry (the world’s largest clinical database specifically dedicated to heart preservation), now with over 1500 enrolled patients who have undergone heart transplantation, the data generated by the researchers continues to show improved clinical outcomes when utilizing Advanced Organ Preservation with the SherpaPak in a direct comparison to traditional ice storage. We are satisfied witnessing a paradigm shift in the standard of care for donor organ preservation, and we are thrilled to be at the forefront of that movement, providing every possible advantage for our transplant patients.New case studies can be used in randomized trial, especially those with prolonged ischemia times in a few years’ time. [ABSTRACT FROM AUTHOR]

Background. Resveratrol (RES) is a polyphenolic compound and natural phytoalexin that plays a potential role in various human diseases. Studies have confirmed that RES has an important function in cardioprotection. Objectives. To investigate the effect of RES on HO-1 protein expression in rat heart after different duration of hypothermic preservation. Material and methods. The Langendorff model of isolated rat heart was used. After being stored in 4°C different Celsior solution for 9 h, Sprague-Dawley rats hearts were divided into 6 groups randomly: control group, 9 h group, 3 μM RES group, 10 μM RES group, 30 μM RES group, and 100 μM RES group. The morphological changes of cardiomyocytes were detected with the hematoxylin & eosin (H&E) staining using a light microscope. The mRNA and protein expression of HO-1 were detected using reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. Results. Compared with the control group, cardiomyocytes were obviously injured in the 9 h group and the protein and mRNA expression of HO-1 were obviously decreased. Compared with the 9 h group, the mRNA and protein expression of HO-1 were increased in dose-dependent manner in the 3 μM RES, 10 μM RES and 30 μM RES group. Compared with the 9 h group, rat myocardial injury was gradually alleviated in 3 μM RES, 10 μM RES and 30 μM RES groups. However, the rat myocardial injury in the 100 μM RES group showed no more obvious improvement than in the 30 μM RES group. Conclusions. In the isolated rat heart, RES protects cardiomyocytes against hypothermic preservation injury through increasing HO-1 protein expression. [ABSTRACT FROM AUTHOR]

Background: Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non‐ischemic perfusion for our ongoing pig‐to‐baboon cardiac xenotransplantation project. Methods: Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1‐ KO/hCD46/hTBM) as donors and captive‐bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non‐ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin‐containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti‐non‐Gal‐antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient's kidney, liver and coagulation functions. Results: In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti‐non‐Gal‐antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions: While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi‐organ failure in more than half of the xenotransplantation experiments. In contrast, cold non‐ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long‐term results after cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation.Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint.Results:Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci.Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.

The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided. [ABSTRACT FROM AUTHOR]

Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint. Results: Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci. Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study was to investigate endothelium dependent relaxation (EDR) in coronary artery and the myocardial contractility after 24 h of non-ischemic heart preservation (NIHP). Design. Explanted cardioplegic hearts from six pigs were preserved by NIHP for 24 h. The perfusion medium consisted of an albumin containing hyperoncotic cardioplegic nutrition-hormone solution with erythrocytes to a hematocrit of 10%. Coronary artery ring segments were then studied in organ baths. Thromboxane A2 was used for vasocontraction and Substance P to elicit endothelium dependent relaxation. A heart trabecula from the right ventricle was mounted in an organ bath and a special stimulation protocol was used to characterize myocardial contractility. Fresh cardioplegic hearts from 11 pigs were used as controls. The water content of the hearts was calculated. Results. There was no significant difference between NIHP and fresh controls regarding EDR (91.2 ± 1.2% vs 93.1 ± 1.8%). The contraction force, potentiation and calcium recirculation fraction did not differ between the groups. The water content of the myocardium was 79.3 ± 0.2% for NIHP and 79.5 ± 0.2% for controls. Conclusions. NIHP for 24 h keeps coronary artery EDR and myocardial contractility intact and causes no edema. [ABSTRACT FROM AUTHOR]

Purpose: Windkessel impedance analysis has proven to be an effective technique for instituting artificial afterload on ex situ hearts. Traditional fixed parameter afterload modules, however, are unable to handle the changing contractile conditions associated with prolonged ex situ heart perfusion. In this paper, an adjustable afterload module is described comprising of three fully adjustable sub-components: a systemic resistor, a proximal resistor and a compliance chamber. Methods: Using a centrifugal pump, the systemic resistor and compliance chamber were subjected to testing across their operating ranges, whereby the predictability of resistance and compliance values was evaluated. The components were then assembled, and the full module tested on three separate porcine hearts perfused for 6 h with success defined by the ability to maintain physiological systolic and diastolic aortic pressures across flow rate variability. Results: For both the systemic resistor and compliance chamber, experimental measurements agreed with their theoretical equivalents, with coefficients of determination of 0.99 and 0.97 for the systemic resistor and compliance chamber, respectively. During ex situ perfusion, overall 95% confidence intervals demonstrate that physiological systolic (95–96.21 mmHg) and diastolic (26.8–28.8 mmHg) pressures were successfully maintained, despite large variability in aortic flow. Left ventricular contractile parameters, were found to be in line with those in previous studies, suggesting the afterload module has no detrimental impact on functional preservation. Conclusions: We conclude that due to the demonstrable control of our afterload module, we can maintain physiological aortic pressures in a passive afterload working mode across prolonged perfusion periods, enabling effective perfusion regardless of contractile performance. [ABSTRACT FROM AUTHOR]

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ughetto, Roubille, Molina, Battistella, Gaudard, Demaria, Guihaire, Lacampagne and Delmas.)

Aims: Guidelines for management of patients with heart failure with mid‐range ejection fraction [HFmrEF; left ventricular EF (LVEF) 41–49%] do not exist. Disagreement exists whether HFmrEF should be considered a distinct group. The aim of this study is to examine characteristics of patients with HFmrEF with HF with reduced EF (HFrEF; LVEF ≤ 40%) or preserved EF (HFpEF; LVEF ≥ 50%). Methods and results: We examined data collected in the American College of Cardiology's National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) Registry® for first HF patient visits between 1 May 2008 and 30 June 2016. Analysis was performed using ANOVA F‐tests (or Kruskal–Wallis tests for non‐normally distributed variables) for continuous parameters and χ2 tests for nominal covariates at the first diagnosed HF visit. Given the NCDR PINNACLE Registry® is a US‐based registry, we opted to define HFmrEF as per the US guidelines, which define HFmrEF as LVEF 41–49% in contrast to European guidelines, which define HFmrEF as LVEF 40–49%. Among 1 103 386 patients with available data, 36.1% (N = 398 228) had HFrEF, 7.5% (N = 82 292) had HFmrEF, and 56.5% (N = 622 866) had HFpEF. Compared with patients with HFrEF or HFpEF, patients with HFmrEF had more prevalent coronary and peripheral artery disease and more history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery (all P < 0.001). Patients with HFmrEF were also more likely to have atrial fibrillation/flutter, diabetes, and chronic kidney disease and to have a history of tobacco use (both P < 0.001). Among those with EF assessment prior to this analysis, only 4.8% (N = 1032) previously had HFrEF that improved to HFmrEF; 32.9% (N = 7072) had HFpEF previously and progressed to HFmrEF. Those patients who transitioned from HFpEF to HFmrEF had considerably more complex profiles and were less aggressively managed compared with those who remained with HFmrEF (all P < 0.001). Conclusions: In this large descriptive analysis, patients with HFmrEF had an atherothrombotic phenotype distinct from other forms of HF. Interventions aimed at treating coronary ischaemia and addressing prevalent risk factors may play a particularly important role in the management of patients with HFmrEF. [ABSTRACT FROM AUTHOR]

Oxidative stress is involved in the pathogenesis of ischemia-reperfusion during myocardial transplantation. Therefore, graft preservation solutions may be improved by supplementation with antioxidants to minimize graft dysfunction caused by cold ischemic injury. Propolis is a polyphenol-rich substance which has an important antioxidant activity. The protective effect of propolis against oxidative stress induced by prolonged cold preservation of heart was investigated. Mice were subjected to a hypothermic model of ischemia in which hearts were preserved for 24 h at 4 °C in Krebs-Hensleit (KH) solution in the absence or presence of propolis concentrations (50, 150 and 250 μg/ml). Levels of released Lactate dehydrogenase (LDH), Creatine phosphokinase (CPK) and Troponine-I (Trop I) were assessed in the preservation solution and histological assessement of heart ischemia injuries was performed. Oxidative stress biomarkers malondialdehyde (MDA) and advanced oxidation protein products (AOPP) and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were assessed in cardiac tissue. Mitochondria were isolated from stored hearts and production of reactive oxygen species (ROS) was tested. Propolis supplementation protected efficiently hearts during preservation by reducing significantly levels of lipids and proteins oxidation and restoring activities of antioxidant enzymes. Also, propolis preserved tissue integrity altered by hypothermic ischemia in a concentration-dependent manner. Propolis reduced significantly the rate of H 2 O 2 produced by mitochondrial respiration, the best antioxidant effect being obtained at the highest propolis concentration (250 μg/ml). Algerian propolis is a non-temperature sensitive scavenger that protects heart from oxidative damage induced by prolonged hypothermic ischemia. [ABSTRACT FROM AUTHOR]

The current study aimed to evaluate whether luteolin could improve long-term heart preservation; this was achieved by evaluating the heart following long-term storage in University of Wisconsin solution (the control group) and in solutions containing three luteolin concentrations. The effects of different preservation methods were evaluated with respect to cardiac function while hearts were in custom-made ex vivo Langendorff perfusion systems. Different preservation methods were evaluated with respect to the histology, ultrastructure and apoptosis rate of the hearts, and the function of cardiomyocytes. In the presence of luteolin, the rate pressure product of the left ventricle was increased within 60 min of reperfusion following a 12-h preservation, coronary flow was higher within 30 min of reperfusion, cardiac contractile function was higher throughout reperfusion following 12- and 18-h preservations, and the left ventricle peak systolic pressure was significantly higher compared with the control group (all P<0.05). The expression levels of apoptosis regulator Bax and apoptosis regulator Bcl-2 in the luteolin groups were significantly decreased and increased, respectively. Lactate dehydrogenase, creatine kinase and malondialdehyde enzymatic activity was increased following long-term storage, while the activity of superoxide dismutase was significantly decreased. Furthermore, luteolin inhibited L-type calcium currents in ventricular myocytes under hypoxia conditions. Thus, luteolin demonstrated protective effects during long-term heart preservation in what appeared to be a dose-dependent manner, which may be accomplished through inhibiting hypoxia-dependent L-type calcium channels. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Isochoric (constant volume) preservation at subfreezing temperatures is being investigated as a novel method for preserving cells and organs. This study is a first initial effort to evaluate the efficacy of this method for heart preservation, and to provide a preliminary outline of appropriate preservation parameters. To establish a baseline for further studies, rat hearts were preserved in a University of Wisconsin (UW) intracellular solution for one hour under isochoric conditions at: 0 °C (atmospheric pressure - 0.1 MPa), - 4 °C (41 MPa), - 6 °C (60 MPa) and – 8 °C (78 MPa). The viability of the heart was evaluated using Langendorff perfusion and histological examination. The physiological performance of hearts preserved at – 4 °C (41 MPa) was comparable to that of a heart preserved on ice at atmospheric pressure, with no statistically significant difference in histological injury score. However, hearts preserved at −4 °C displayed substantially reduced interstitial edema compared to hearts preserved by conventional hypothermic preservation in UW on ice at atmospheric pressure, suggesting significant protection from increased vascular permeability following preservation. Hearts preserved at – 6 °C (60 MPa) suffered injury from cellular swelling and extensive edema, and at – 8 °C (78 MPa) hearts experienced significant morphological disruption. To the best of our knowledge, this is the first publication showing that a mammalian organ can survive low subfreezing temperatures without the use of a cryoprotective additive. Lowering the preservation temperature reduces metabolism and improves preservation quality, and these results suggest that improvements in preservation are possible at subzero temperatures with low to moderate pressures observed at −4 °C. Notably, tissue damage was observed at lower temperatures (−6 °C or below) accompanying further elevation of pressure associated with isochoric preservation that may prove detrimental. Therefore, subfreezing temperature isochoric preservation protocols should optimize, a combination of temperature and pressure that will minimize the negative effects of elevated pressure while retaining the beneficial effect of lower temperatures and reduced metabolism. [ABSTRACT FROM AUTHOR]

In agreement with the last will of Doge Francesco Erizzo († 1646), his heart was buried in San Marco, the political and religious center of the Serenissima, next to the high altar and thus ad sanctos to the relics of Venice's patron saint. This unprecedented privilege not only disrupted the city's restrictive policies concerning public monuments, but her republican ideals in general. Due to the significance of the heart in Christian eschatological thinking and corporal state doctrines his burial elevated Erizzo to the status of an absolute ruler threatening the Republic's sacred constitution. In Venice, however, individual and public interests were closely intertwined. This study therefore analyzes the heart burial in the context of Erizzo's self-fashioning, Venetian state ideology, devotional practices and collective memory. [ABSTRACT FROM AUTHOR]

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation. [ABSTRACT FROM AUTHOR]

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling. [ABSTRACT FROM AUTHOR]

Aging is associated with extensive remodeling of the heart, including basement membrane (BM) components that surround cardiomyocytes. Remodeling is thought to impair cardiac mechanotransduction, but the contribution of specific BM components to age-related lateral communication between cardiomyocytes is unclear. Using a genetically tractable, rapidly aging model with sufficient cardiac genetic homology and morphology, e.g. Drosophila melanogaster , we observed differential regulation of BM collagens between laboratory strains, correlating with changes in muscle physiology leading to cardiac dysfunction. Therefore, we sought to understand the extent to which BM proteins modulate contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin , Laminin A , and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression correlated with an overall preservation of contractile velocity with age and extension of organismal lifespan. Global heterozygous knockdown confirmed these data, which provides new evidence of a direct link between BM homeostasis, contractility, and maintenance of lifespan. [ABSTRACT FROM AUTHOR]

This work proposes a method to perform elemental identification on plasmas produced using the laser-induced breakdown spectroscopy (LIBS) technique. The method is based on the preservation of the relative relevance of the spectral line emission intensities, which is lost during the parametric correlation procedure, by the introduction of a similitude coefficient called wavelength similarity coefficient. Furthermore, it was shown that for identification purposes, a simplified plasma model is sufficient to predict adequately the relative emission intensities in LIBS plasmas. As a result, it is possible to automatically identify the species with high emission signals, while trace detection is also possible by relaxing search conditions, although manual refinement is still required. [ABSTRACT FROM AUTHOR]

Background The Organ Care System, an ex-vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. It is unknown whether using the Organ Care System influences 2-year outcomes after heart transplantation. We reviewed our institutional experience to compare 2-year outcomes for patients randomized to the Organ Care System or standard cold storage. Methods Between 2011 and 2013, heart transplant candidates from a single tertiary-care medical center enrolled within the PROCEED II trial were randomized to either standard cold storage or the Organ Care System. Outcomes assessed included 2-year survival, freedom from cardiac allograft vasculopathy (CAV), non-fatal major cardiac events (NF-MACE), biopsy-proven cellular rejection (CMR) and biopsy-proven antibody-mediated rejection (AMR). Results Thirty-eight patients were randomized to the Organ Care System ( n = 19) or cold storage group ( n = 19). There was no significant difference in 2-year patient survival (Organ Care System: 72.2%; cold storage: 81.6%; p = 0.38). Similarly, there were no differences in freedom from CAV, NF-MACE, CMR or AMR. The Organ Care System group had significantly longer total ischemia time (361 ± 96 minutes vs 207 ± 50 minutes; p < 0.001) and shorter cold ischemia time (134 ± 45 minutes vs 207 ± 50 minutes; p < 0.001) compared with the cold storage group. Conclusion The Organ Care System did not appear to be associated with significant differences in intermediate results compared with conventional strategies. These results suggest that this ex-vivo allograft perfusion system is a promising and valid platform for donor heart transportation. [ABSTRACT FROM AUTHOR]

Background: Hydrogen sulfide (H 2 S) is known for its unpleasant odor and severe toxicity. However, an in-depth study of H 2 S showed that it can be used as an important messenger, which can play important physiological and pathological roles in vitro and in vivo . In recent years, the application of H 2 S in the field of cardiac preservation has attracted the interest and attention of scholars worldwide. H 2 S plays an effective and protective role in cardiac ischemia/reperfusion injury through antioxidant, anti-inflammatory, and antiapoptotic mechanisms., Objective: The purpose of this study is to analyze the current scientific achievements on the application of H 2 S in the field of cardiac preservation and to provide new ideas for further research., Methods: TS = ("hydrogen sulfide" OR "hydrogen sulfide") AND TS = ("cardiac" OR "heart" OR "myocardium" OR "hearts") AND TS = ("reperfusion" or "transplantation" or "implanted" or "transplant" or "implantation" or "migration" or "preservation" or "grafting" OR "ischemia" OR "perfusion" or "conservation" or "preserve" or "reservation") AND DT = (Article OR Review) AND LA = (English) were used as search strategies for data collection from the Science Citation Index-Expanded database of the Web of Science Core Collection. CiteSpace 5.8. R3 and Microsoft Office Excel 2019 were used for data analysis., Results: A total of 429 related articles were included, and the total number of articles showed a fluctuating upward trend. We used CiteSpace 5.8. R3 and Microsoft Excel 2019 to evaluate and visualize the results, analyzing institutions, countries, journals, authors, co-cited references, and keywords., Conclusions: As increasing evidence shows that H 2 S plays an indispensable role in the field of cardiac preservation, its mechanistic research and clinical application may become the main focus of future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhou, Wu, Sun, Meng, Zhang and Zhao.)