Organ Donation Programs Research Articles

A local, non-commercial tissue bank connected to an organ donor program can produce musculoskeletal allografts of uniform quality at very low costs – ten years’ experience

It is common practice that allograft tissues for knee multiligament reconstruction, meniscus transplantation, cartilage replacement and other advanced procedures are made available through commercial banks. The aim was to present the 10-year experience with a local, non-commercial tissue bank, established in 2014. The allograft bank was connected to an existing organ donor program. Following organ procurement, the musculoskeletal tissue is removed and stored immediately, fresh frozen to − 80 degrees Celsius (except hyaline cartilage, which is stored at 5 degrees Celsius). The donor is tested for contagious disease and the grafts for bacteria. When all results are negative, the grafts are released. When thawed before use a swap is cultured. Consecutive, prospectively collected data were analyzed. There were 31 donations, resulting in 1160 grafts. Only 40 grafts (3.4%) had a positive bacteria culture and were discarded. 552 recipients have been treated by use of these allografts. All grafts had negative bacterial cultures in swaps obtained before thawing, and there were no recorded transplantation related complications. The expenses for local grafts were 10–15% of the costs for grafts obtained from foreign banks. Through the local donation program, it was possible to establish a tissue bank with controlled quality grafts at minimal costs, minimizing the need for transportation of frozen grafts retrieved in other countries. Centers for specialized orthopedic surgery using allograft tissue can be self-providing and reduce costs by retrieving and handling allograft tissues locally.

Challenges and Opportunities in Deceased Organ Donation Program: Insights from a Tertiary Care Hospital in South India

Background: Organ transplantation is a critical medical intervention for patients with end-stage organ failure. Deceased organ donation plays a pivotal role in meeting the demand for organs. However, there exists a significant disparity between the need for organs and their availability, especially in low-income countries. India, despite its potential donor pool, faces a severe shortage of organs for transplantation. Materials and Methods: This retrospective study analyzed hospital records of 116 potential deceased organ donors from 2013 to 2020. Data encompassed demographics, next-of-kin consent for organ transplantation, and circumstances of injury. Results: Results revealed that 85.34% of potential donors were men, and 14.66% were women. After counseling, 71.55% (83/116) of the families consented to deceased organ donation. Most potential donors fell within the 21–30 age group (25.88%). The majority of donors (80.17%) died due to road traffic accidents (RTAs), primarily two-wheeler drivers constituted the largest group of deceased (51.72%). Conclusion: Bridging the gap between organ demand and supply in India necessitates addressing the lack of awareness regarding brain death and organ transplantation. Collaborative efforts involving NGOs, healthcare institutions, media, and government bodies are essential to raise awareness and improve donation rates, especially in public health centers. Establishing guidelines for compassionate discussions with families about organ donation is imperative.

Improving long-term kidney allograft survival by rethinking HLA compatibility: from molecular matching to non-HLA genes.

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and post-transplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation.

Connecting D.O.T.S.: An Education on an Organ Donation and Transplantation Program for Schools.

Education of the public on organ donation and transplantation may be the best way to increase awareness of this lifesaving practice. Research has shown that children are open to learn about these topics. After a long journey that started with the pioneer work of Dr. Felix Cantarovich (Argentina), the positive impact of Dr. William Wall in Canadian schools, followed by the "First Global Forum on Organ Donation and Transplantation for Schools" (The Transplantation Society, 2012), the joint 2017 working group of the Canadian Society of Transplantation and The Transplantation Society, and the work of Professor Dr. Marion Siebelink (Netherlands), we were able to arrive to "Connecting D.O.T.S." (Donation and Organ Transplantation for Schools). The Connecting D.O.T.S. platform is an online, free, and easy to access platform from The Transplantation Society dedicated to educating schoolchildren around the globe on donation and organ transplantation, with modules for students, teachers, and parents.

Abstract A057: Investigating Fibroblast-Epithelial crosstalk in pre-malignant and cancerous microenvironment

Abstract Pancreatic ductal adenocarcinoma (PDAC) originates from precursor lesions, the most common of which are known as pancreatic intraepithelial neoplasia (PanIN). PanIN formation and progression is accompanied by accumulation of a precursor microenvironment (PME) composed of desmoplastic stroma that plays an important role in promoting tumor growth and immune evasion. The crosstalk between tumor cells and stromal cells is an area of active investigation. While PanIN and the PME have been extensively studied in mouse models, their nature in humans have remained elusive as there is no clinical indication to sample healthy pancreas. Through a unique collaboration with the Gift of Life Organ and Tissue donation program, we performed transcriptomic analysis on normal pancreata declined for transplant. We noted that epithelial cells in the PanIN and cancer microenvironment were transcriptomically similar; however, their surrounding stromal fibroblasts were markedly distinct. Given that most precursor lesions remain quiescent while some progress to tumor, we sought out to elucidate how the transcriptional programs in epithelial cells influence fibroblast cell fate. To do so, we developed a 3D ex-vivo organoid-fibroblast coculture system using primary organoid and fibroblast cultures successfully derived from Gift of Life pancreata or PDAC patients undergoing surgical resection. Our coculture system retains histological features of heterogeneity observed in vivo. Using single cell RNA-sequencing analysis of matched fibroblast-organoid cocultures we identified factors that were highly expressed in fibroblasts in tumor cocultures, but not in normal cocultures. We are currently interrogating candidate ligand/receptor interactions in our cocultures to determine the mediators of this epithelial-mediated fibroblast polarization. This model will allow us to gain an understanding about how components of the microenvironment restrain or promote malignant transformation and serve as a great tool to study therapies targeting tumor and stromal cells in a patient specific manner. Citation Format: Padma Kadiyala, Ahmed Elhossiny, Jianhua Liu, Alexander Bray, Katelyn Donahue, Arvind Rao, Jiaqi Shi, Yaqing Zhang, Filip Bednar, Timothy Frankel, Eileen Carpenter, Marina Pasca Di Magliano. Investigating Fibroblast-Epithelial crosstalk in pre-malignant and cancerous microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A057.

243.1: A performance review of the cadaveric organ donation program in an Indian State.

243.1: A performance review of the cadaveric organ donation program in an Indian State.

What Italian PICU Healthcare Providers Think About Donation After Cardiocirculatory Determination of Death: A National Survey

ABSTRACTBackgroundItaly presently does not have a pediatric organ donation program after cardiocirculatory determination of death (pDCDD). Before implementing a pDCDD program, many centers globally have conducted studies on the attitudes of pediatric intensive care unit (PICU) staff. This research aims to minimize potential adverse reactions and evaluate the acceptance of the novel donation practice.MethodsWe conducted an electronic and anonymous survey on attitudes toward pDCDD among healthcare professionals (HCPs) working at eight Italian PICUs. The survey had three parts: (I) questions about general demographic data; (II) 18 statements about personal wishes to donate, experience of discussing donation, and knowledge about donation; (III) attitudinal statements regarding two pediatric Maastricht III scenarios of organ donation.ResultsThe response rate was 54.4%, and the majority of respondents were nurses. Of those who responded, 45.3% worked in the Center, 40.8% in the North, and 12.8% in the South of Italy. In total, 93.9% supported pediatric organ and tissue donation, 90.3% supported donation after neurological determination of death (DNDD), 78.2% supported pDCDD, and 69.7% felt comfortable about the idea of participating in pDCDD on Type III patients, with a higher percentage of supportive responses in the Center (77.2%) than in the North (65.1%) and South (54.5%) of Italy (p‐value < 0.004). Concerning scenarios, 79.3% of participants believed that organ retrieval took place in a patient who was already deceased. Overall, 27.3% considered their knowledge about DCDD to be adequate.ConclusionsOur study provides insight into the attitudes and knowledge of PICU staff members regarding pDCDD in Italy. Despite a general lack of knowledge on the subject, respondents showed positive attitudes toward pDCDD and a strong consensus that the Italian legislation protocol for determining death based on cardiocirculatory criteria respects the “dead donor rule.” There were several distinctions among the northern, central, and southern regions of Italy, and in our view, these disparities can be attributed to the varying practices of commemorating the deceased. In order to assess how practice and training influence the attitude of PICU staff members, it would be interesting to repeat the survey after the implementation of a program.

Effect of the Organ Donation Quality System on Donation Activity of Warsaw Hospitals.

BACKGROUND Like many other countries, Poland faces a shortage of transplantable organs despite implementing strategies to develop donation programs. Increasing the effectiveness of deceased organ donation programs requires the implementation of protocols and quality standards for the entire process. The aim of this study was to assess the organ donation potential in Warsaw hospitals (with and without implemented donation procedures) in the years 2017-2018, before the COVID-19 pandemic affected donation activity. The obtained results were compared with quality indicators established in the ODEQUS project and the European Commission project "Improving Knowledge and Practices in Organ Donation" (DOPKI). MATERIAL AND METHODS Retrospective analysis was performed of hospitalization and death causes (including deaths in the brain death mechanism) in the hospitals and intensive care units in 2017-2018. We divided 15 Warsaw hospitals into 2 groups: those with implemented quality programs for organ donation (n=4) and those without such programs (n=11). RESULTS Hospitals with procedures obtained significantly higher values than hospitals without procedures, but were lower than the values in DOPKI and ODEQUS. The success rate of the organ donation process after brain death recognition was comparable in all groups. The conversion rate to actual donors was 73% in hospitals with procedures compared to 68% in hospitals without procedures, significantly higher than in the 42% reported in the DOPKI project. CONCLUSIONS Low numbers of brain death declarations in Warsaw hospitals result from low recognition of deaths in the brain death mechanism. Implementing procedures at each hospital level will enable identification of critical points and comparison of solution outcomes.

Knowledge, Attitude, and Practice of Organ Donation Among the Population of Al-Majma'ah Region, Saudi Arabia.

Organ donation plays a pivotal role in addressing the global demand for transplantable organs and saving lives. The success of organ transplantation relies not only on medical advancements but also on the willingness of communities to participate in organ donation programs. In Saudi Arabia, specifically within the Al-Majma'ah region, understanding the dynamics of knowledge, attitudes, and practices related to organ donation is crucial for promoting a sustainable and ethical organ donation system. A cross-sectional, retrospective study was utilized in this research, employing data from a sample of 564 participants from the general population of the Al-Majma'ah region, Saudi Arabia. The participants completed a self-administered questionnaire and ensured anonymity. About 545 (96.6%) respondents were familiar with the concept of organ donation, and 455 (80.7%) participants recognized the necessity for the blood groups of the donor and recipient to match before the transplant process. About 412 (73.0%) participants agreed with the practice of organ donation with 326 (57.8%) expressing support for the practice. About 417 (73.9%) participants reported that their religion permits or endorses organ donation/transplantation. A total of 151 individuals (26.8%) had a low knowledge level, with total scores below 50%(6 or lower). In contrast, 280 people (4.7%) demonstrated a moderate level of knowledge (scoring between 50% and 75%) (7 to 9). Additionally, 133 individuals (23.5%) showcased a high level of knowledge, with scores exceeding 75%(10 or higher). The study established a statistically significant association between age, marital status with p-values < 0.05 (0.001*), and the knowledge score towardorgan donation. However, genderand monthly household income were not significantly associated with knowledge score towardorgan transplant with p-values (p-value > 0.05). The research findings indicated a moderate level of knowledge and a positive attitude toward organ donation among the general population of the Al-Majma'ah region in Saudi Arabia. Age and marital status were found to be significantly associated with the knowledge score towardorgan donation. The study noted the desire and willingness to save lives through organ donation by the residents of the Al-Majma'ah region in Saudi Arabia.

Early experiences of deemed consent legislation for organ donation in Nova Scotia: a qualitative study.

In 2021, Nova Scotia, Canada, became the first jurisdiction in North America to adopt a deemed consent organ donation system under its revised Human Organ and Tissue Donation Act. This study sought to understand the early experiences of program staff and clinicians involved in implementing this legislation. We conducted semistructured interviews with members of the provincial organ donation program and intensive care unit and emergency department clinicians (n = 14). Two investigators coded transcripts of interviews, then categorized the coded data into themes. We identified four key themes: 1) legislation has limited impact on daily practice; 2) legislation does not address existing barriers; 3) legislation aids conversations with donor families; and 4) legislation should provide more autonomy to patients and families, not less. Deemed consent legislation had limited impact on clinician's day-to-day practices, because of lack of infrastructure changes and infrequent donation opportunities. Nevertheless, participants felt the introduction of deemed consent in Nova Scotia eased conversations between families of potential donors and clinicians. These findings should be used to inform ongoing implementation of deemed consent and be considered by those contemplating similar legislative changes.

Organ Donation in Canadian PICUs: A Cross-Sectional Survey, 2021-2022.

To understand contemporary pediatric organ donation programs in Canadian PICUs, including: policies and practices, data collection and reporting, and system and process barriers. A cross-sectional survey carried out 2021-2022. Canadian PICUs affiliated with a donor physician network. Pediatric intensivists identified as the donation program lead, or most knowledgeable about donation for their institution. A 19-item survey was developed through collaboration with stakeholders from the organ donation and transplantation community within Canada. Domains and items were generated and reduced iteratively during an in-person workshop. Pretesting and pilot testing were completed to ensure readability, flow, clinical sensibility, and construct validity. Fifteen of 16 (94%) invited Canadian PICUs from seven provinces completed the survey representing 88% (15/18) of all noncardiac Canadian PICUs. Surveys were completed between June 2021 and September 2022. All units support donation after death by neurologic criteria (DNC); 14 of 15 indicated donation policies were in place and 1 of 15 indicated no policy but the ability to facilitate donation. Thirteen of 15 units (87%) support donation after death by circulatory criteria (DCC) with policies in place, with 11 of 13 of these indicating routine support of donation opportunities. The majority (13/15) of units identified a donation champion. Of the 16 identified champions across these centers, 13 were physicians and were registered nurses or nurse practitioners. Eight of 13 units (62%) with donation champions had positions supported financially, of which 5 units came from the Organ Donation Organization and the other 3 came from the provincial health authority. Finally, only 3 of 15 PICU donation programs have a pediatric donation committee with family involvement. Variability exists in identification (including determination of death practices), referral, and approach for donation between units. Although all Canadian PICUs support donation after DNC donation, and most support donation after DCC, variability exists in the identification, referral, and approach of potential donors. There is a notable lack of family involvement in pediatric donation programs. There are many opportunities for standardization of PICU donation programs which may result in improved rates of pediatric organ donation in Canada.

Attitudes and factors influencing organ donation decision-making in Damascus, Syria: a cross-sectional study

Organ donation is vital to saving lives, but its success depends on people's willingness to donate organs. This descriptive cross-sectional survey aimed to investigate attitudes towards organ donation in Damascus, Syria. Understanding attitudes is crucial for the success of organ donation programs, especially in countries with similar settings. This study was a descriptive cross-sectional survey aimed at understanding patients’ attitudes towards organ donation in Damascus, Syria. Data was collected through a carefully constructed validated survey through face-to-face interviews. 600 participants were randomly interviewed, 62.8% agreed to donate their organs after death, with helping others being the primary reason. Religious beliefs were the primary reason for organ refusal in males, while for females, it was lack of knowledge and religious beliefs. However, there were no significant differences between genders or educational level and age groups in the acceptance of organ donation. The percentage of those who agree to donate their organs after death encourages taking an effective step to build an integrated donation system, not just a center. Bearing in mind that there is no correlation with age, gender or even educational level, which means that the system may include different groups of society.

Development of the Nova Scotia Potential Donor Audit (PDA) Tool and 2020 Historic Performance Database: Lessons Learned From the First 1000 Medical Record Reviews.

Legislation and accountability frameworks are key components of high-performing deceased-donation systems. In 2021, Nova Scotia (NS), Canada, became the first jurisdiction in North America to enact deemed consent legislation and concurrently implemented mandatory referral legislation similar to that found in other Canadian provinces. Frontline financial resources were provided by the government to support the development of program infrastructure, including implementation of means to evaluate system performance. The Organ Donation Program (ODP), in collaboration with other stakeholders, developed a Potential Donor Audit (PDA) tool and database for referral intake and manual performance audits. Medical record reviews of deaths in the year before legislative change were conducted to pilot and revise the PDA and evaluate missed donation opportunities. The NS PDA was piloted on 1028 patient deaths. Of 518 patients (50.4%) who met clinical triggers for referral to the ODP, 72 (13.9%) were referred (86.1% missed referral rate). One hundred sixty-three patients met the NS definition of a potential donor; 53 (32.5%) were referred (110 missed potential donors). Referral consent rates reached 71.7% (n = 38 of 53 approaches). The actualized donation rate reported by Canadian Blood Services was 29.9 donors per million population (n = 34 donors). We documented high rates of missed referrals and missed potential donors before the enactment of mandatory referral and deemed consent legislation. The ODP has intentionally broadened clinical criteria for referral to shift the responsibility of identifying medically suitable potential donors from bedside clinicians to organ donation specialists. Lessons learned from our experience developing a PDA include the importance of early involvement of multiple stakeholders and ongoing modification of fields and workflow based on data availability and utility for clinical, educational, research, and reporting purposes.

255 Attitudes and Perceptions Among Iraqi Young Adults Towards Organs Donation and Transplantation: A Call for Action

Abstract Aim Organ’s transplantation is the only treatment for end-stage organ failure. However, the disparity between organs availability and the number of patients in the waiting lists is widening globally, especially in Iraq for many reasons. This study aims to assess the level of attitudes and perceptions among Iraqi young adults towards organs donation and transplantation as the first study to be conducted in Iraq for such purpose. Method This observational study was conducted among 912 Iraqi young adults through a structured questionnaire which was disseminated among social media platforms. Participants consented before filling the questionnaire and their responses were analyzed to test the hypothesis of the study. Results Most of the participants were females, Muslims and in their undergraduate level. Overall, 84.2% of the participants were willing to donate their organs after death and (97.9%) of them actually agreed to sign for organs donation. Most of those who were not willing to donate have no idea whether their religion approves it or not. There was no statistically significant difference in willingness to donate between different socioeconomic classes or residency areas. Conclusions Most of the participants are convinced with donating their organs after death and are willing to sign for organ donation programs, advocating for initiating an official governmental transplant agency with multiple local committees distributed among health directorates all over the country managing it. The hesitancy to donate organs was attributed mostly to religious and associated with lack of knowledge issues, thus education might be the key to positive attitudes.

Healthcare System Impact on Deceased Organ Donation and Transplantation: A Comparison Between the Top 10 Organ Donor Countries With 4 Countries in Southeast Asia.

The need for organ donation is constantly increasing. Some countries have made improvements, while others, such as countries in Southeast Asia (SEA), have some of the lowest rates of deceased donors (pmp). This review aims to compare 14 countries with regards to many variables related to healthcare systems. Countries leading in deceased organ donation spend more on health and education, which is associated with increased potential for deceased organ donation. Out-of-pocket expenditure, is also associated with a decrease in deceased organ donation. Countries in SEA are lacking in healthcare resources such as workforce and materials, which are both necessary for a successful transplant program. Most countries in SEA have an excellent foundation for successful organ donation systems, including proper legislation, government support, and brain death laws along with an overall acceptance of brain death diagnosis. Priorities should include improving coordination, donor identification, and healthcare worker education. Countries in SEA have a lot of potential to increase deceased organ donation, especially by investing in healthcare and education. There is no one size fits all for organ donation programs and countries in SEA should focus on their strengths and take cultural differences into consideration when planning interventions.

Collaborative Approach to Organ Donation in a Level II Trauma Center

Although a shortage of organ donors is a continuing global problem in health care, obtaining authorization for donation after an individual experiences a traumatic nonsurvivable event can be difficult.To improve organ donation practices at a level II trauma center.After reviewing trauma mortality cases and performance improvement metrics with their organ procurement organization's hospital liaison, leaders at the trauma center implemented a multidisciplinary performance improvement initiative to engage the facility's donation advisory committee, provide education for staff members, and increase program visibility to create a more donation-friendly culture for the facility.The initiative led to an improved donation conversion rate and a greater number of organs procured. Continued education increased staff and provider awareness of organ donation, contributing to the positive outcomes.A multidisciplinary initiative that includes continuing staff education can improve organ donation practices and program visibility, ultimately benefiting patients in need of organ transplantation.

The National Organ Donation and Transplantation Program in Greece: Gap Analysis and Recommendations for Change.

Greece has fallen far behind many comparable European countries in the field of organ donation and transplantation and has made little progress over the past decade. Despite efforts to improve its organ donation and transplantation program, systemic problems persist. In 2019, the Onassis Foundation commissioned a report to be prepared by the London School of Economics and Political Science that focused on the state of the Greek organ donation and transplantation program and proposed recommendations for its improvement. In this paper, we present our analysis of the Greek organ donation and transplantation program together with an overview of our specific recommendations. The analysis of the Greek program was undertaken in an iterative manner using a conceptual framework of best practices developed specifically for this project. Our findings were further developed via an iterative process with information provided by key Greek stakeholders and comparisons with case studies that featured successful donation and transplantation programs in Croatia, Italy, Portugal, Spain, and the United Kingdom. Because of their overall complexity, we used a systems-level approach to generate comprehensive and far-reaching recommendations to address the difficulties currently experienced by the Greek organ donation and transplantation program.

A Conceptual Framework for Evaluating National Organ Donation and Transplantation Programs.

Conceptual frameworks are valuable resources that can be used to guide the planning, evaluation, and development of healthcare services. However, there are currently no comprehensive frameworks focused on organ donation and transplantation that identify the critical factors underlying a successful national program. To address this knowledge gap, we developed a conceptual framework that takes into account all major domains of influence, including political and societal aspects as well as clinical implementation. The framework was initially constructed based on a targeted review of the relevant medical literature. Feedback provided by a panel of international experts was incorporated into the framework via an iterative process. The final framework features 16 essential domains that are critical for initiating and maintaining a successful program and improving the health of patients with organ failure. Of particular note, these domains are subject to three overarching health system principles: responsiveness, efficiency, and equity. This framework represents a first attempt to develop a whole-system view of the various factors that contribute to the success of a national program. These findings provide a useful tool that can be adapted to any jurisdiction and used to plan, evaluate, and improve organ donation and transplantation programs.

PO-01-143 HYPOTHERMIA-INDUCED J-WAVES AND ARRHYTHMIAS ARE ASSOCIATED WITH AN EXACERBATION OF REPOLARIZATION RATHER THAN CONDUCTION HETEROGENEITY IN HUMAN HEARTS

The cardiac effects of hypothermia have been studied for many years since the initial discovery of the electrocardiographic J-wave in a case of accidental hypothermia. However, the precise mechanisms underlying the origin of the hypothermic J-wave and associated arrhythmias in man are still debated. A limited number of ex vivo animal studies have focused on the transmural repolarization dispersion, but do not provide global mapping of ventricular activation and repolarization heterogeneities. To map hypothermia-induced electrophysiological changes at a tissue level and study the mechanisms of initiation and maintenance of arrhythmias. Optical mapping experiments were performed on isolated right ventricles (RV) from pigs (N=7) and humans obtained through our organ donation program (N=3 control subjects; N=1 SCN5A BrS-associated mutant subject). Epi- and endocardial (EPI and ENDO) action potential conduction and repolarization properties were assessed at different pacing frequencies and arrhythmias were mapped and quantified at baseline (37°C), during severe hypothermia (29°C), and after a return to normothermia. Hypothermia induced a reversible prolongation of global action potential duration at 80% of repolarization (APD80) in pigs (EPI: +27%, ENDO: +21%; p<0.01) and humans (+45% in both EPI and ENDO), an increase in APD80 dispersion, and steepness of APD restitution curve. Repolarization time dispersion was increased in both species (pigs: +94%, p<0.001 in EPI and +79%, p<0.05 in ENDO; humans: +97% in EPI and +14% in ENDO). The total activation time was significantly prolonged in pigs (EPI: +58%, p<0.001; ENDO: +46%, p<0.01) but not in humans. Arrhythmogenicity was further increased in human ventricles (+43% of spontaneous arrhythmias in pigs versus +100% in humans), which always displayed defibrillation-resistant arrhythmias. In the carrier of a SCN5A mutant, hypothermia additionally potentiated epicardial localized conductive disorders already detected at baseline. Our results indicate that, in humans, and contrary to pigs, the hypothermic J-wave and associated arrhythmogenesis result more from an exacerbation of repolarization rather than conduction heterogeneity. Pre-existing localized conduction heterogeneities within pathological hearts can however contribute to the J-wave phenotype during hypothermia.

PO-01-159 ROLE OF THE SUCCINATE PATHWAY IN ATRIAL FIBRILLATION MECHANISMS

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. The mechanisms underlying the transition from paroxysmal to persistent AF are still a matter of debate. Recent studies indicate a potential role for metabolic remodelling in the AF stabilization process and increased levels of a specific metabolic substrate, succinate, have been found in blood plasma of AF patients. While succinate is known to increase reactive oxygen species (ROS) production, the role of the succinate receptor (GPR91) in atrial function is unknown. To assess the impact of the succinate pathway on AF vulnerability in a sheep model. GPR91 expression levels were quantified by Western Blot (WB) in a previously described sheep model of persistent AF induced by burst-pacing. Optical experiments were subsequently performed in ex vivo right atria (RA) from control sheep (N=5). RA were perfused by Tyrode solution, then supplemented with the cis-epoxysuccinic acid (cESA), a specific activator of GPR91 (150μM) to study its involvement in atrial electrophysiology and AF. Action potential duration at 80% of repolarization (APD80) were assessed from 2 to 5Hz pacing frequency. We used an S1S2 pacing protocol to determine effective refractory period (ERP) and a burst pacing protocol (30Hz) to assess ex vivo AF vulnerability. Finally, an organ donation program allowed us to investigate these properties in a human RA from an AF patient. WB experiments revealed an increase in GPR91 expression in AF sheep compared to sham sheep. Interestingly, in resistant sheep (no AF after 90 days of burst pacing), expression levels were decreased compared to sham. During cESA perfusion in control sheep RA, sinus rhythm (119 vs 95 bpm; p=0,03) and ERP (202 vs 178 ms; p=0,36) were decreased when compared to baseline. We also observed a decrease in APD80 (199 vs 177 ms; p=0.009) and in CV (127 vs 115 cm/sec; p=0.01). These electrophysiological perturbations led to an increase in AF vulnerability by burst pacing (0% vs 60%) and an increase in spontaneous arrhythmias. These results were corroborated in the human RA were cESA decreased APD80 (265 vs 241 ms), ERP (240 vs 220 ms), and CV (119 vs 94 cm/sec) and increased arrhythmia vulnerability. For the first time, we demonstrated that GPR91 is expressed in atrial tissue and that its activation through succinate can play a major role in AF mechanisms.