{"title":"Change in Anticoagulant Strategy During IMPELLA Support and Improved Outcomes.","authors":"Makiko Nakamura, Teruhiko Imamura, Masaki Nakagaito, Toshihide Izumida, Koichiro Kinugawa","doi":"10.1111/aor.70261","DOIUrl":"https://doi.org/10.1111/aor.70261","url":null,"abstract":"<p><strong>Background: </strong>Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has been used as an anticoagulant in patients undergoing extracorporeal circulatory support who have bleeding or heparin-related adverse effects. The safety and efficacy of NM-based anticoagulation in patients receiving Impella support who develop bleeding or thrombocytopenia remain uncertain.</p><p><strong>Methods: </strong>Patients who underwent Impella placement without prior cardiopulmonary resuscitation between 2018 and 2026 at our institution were included. In January 2024, the anticoagulation strategy for patients with bleeding or thrombocytopenia was revised to incorporate NM alone or in combination with low-dose heparin, with selective use of a bicarbonate-based purge solution. Differences in 30-day mortality and survival to discharge between the early era (2018-2023) and the late era (2024-2026) were retrospectively evaluated.</p><p><strong>Results: </strong>A total of 97 patients (median age 70 years; 64% male) were analyzed. The daily amount of transfused red blood cell products during Impella support was significantly lower in the late era (0.8 versus 1.8 units, p = 0.024). 30-day mortality was significantly lower, and survival to discharge was significantly higher in the late era (p < 0.05 for both). Multivariable logistic regression analysis showed that the late era was significantly associated with a higher likelihood of survival to discharge, with an odds ratio of 32.46 (95% confidence interval 4.28-756.14, p < 0.001).</p><p><strong>Conclusions: </strong>The late era, during which a revised anticoagulation strategy incorporating NM and selective use of a bicarbonate-based purge solution was implemented, was associated with lower daily red blood cell transfusion requirements and higher survival to discharge.</p>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elliott Worku, Richard Lee, Ruaidhri Carey, Andre Kyme, Timothy Southwood
{"title":"Cannula Pairing Determines Distal Limb Perfusion During Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation: An Experimental Mock-Loop Study.","authors":"Elliott Worku, Richard Lee, Ruaidhri Carey, Andre Kyme, Timothy Southwood","doi":"10.1111/aor.70250","DOIUrl":"https://doi.org/10.1111/aor.70250","url":null,"abstract":"<p><strong>Background: </strong>Limb ischaemia remains a common complication of peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Reinforced introducer sheaths are commonly used off-label as distal perfusion cannulas; however, their ability to provide adequate distal flow across clinically relevant ECMO configurations remains uncertain. We sought to evaluate the influence of cannula size configurations on distal flow fraction using a simple mock circulatory loop.</p><p><strong>Methods: </strong>Distal flow fraction was evaluated across 24 configurations comprising 15-21Fr arterial return cannulas and 7-9Fr reinforced introducer sheaths. Direct and indirect connection of the DPC to the arterial return cannula was compared. Measurements were obtained at circuit flows from 1 to 5 L/min in 100 mL/min increments.</p><p><strong>Results: </strong>Distal flow fraction significantly decreased with increasing arterial return cannula size (β = -0.796 percentage points; 95% CI, -0.844 to -0.748; p < 0.001), and indirect DPC connection (β = -0.475 percentage points; 95% CI, -0.588 to -0.362; p < 0.001). In comparison, increasing DPC size was overall associated with a small and insignificant augmentation of the distal flow fraction (β +0.098 percentage points per Fr; 95% CI -0.014 to +0.210; p = 0.087). At the lowest circuit flow (1 L/min), the maximum distal flow achieved by any configuration was 86 mL/min.</p><p><strong>Conclusions: </strong>In this controlled hydraulic experiment, larger arterial return cannulas reduced DPC flow relative to total circuit flow. Distal flow was particularly limited at low total circuit flows, potentially compromising limb perfusion during ECMO weaning. These findings support further investigation to evaluate the appropriateness of introducer sheath devices for the purposes of distal limb protection.</p>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura W D Knijff, Asel S Arykbaeva, Sandra W van der Kooij, Dorottya K de Vries, Mieke F van Essen, Ian P J Alwayn, Henri G D Leuvenink, Rutger J Ploeg, Cees van Kooten
{"title":"The Anti-Inflammatory Effect of Normothermic Machine Perfused Human Kidneys on Monocyte-Derived Dendritic Cells.","authors":"Laura W D Knijff, Asel S Arykbaeva, Sandra W van der Kooij, Dorottya K de Vries, Mieke F van Essen, Ian P J Alwayn, Henri G D Leuvenink, Rutger J Ploeg, Cees van Kooten","doi":"10.1111/aor.70251","DOIUrl":"https://doi.org/10.1111/aor.70251","url":null,"abstract":"<p><strong>Background: </strong>The immunomodulatory activity of normothermic machine perfusion (NMP) on donor organs may be reflected by the release of immune-regulating factors into the perfusate. Dendritic cells (DCs) are potent antigen-presenting cells and are able to sense these factors. We hypothesized that activation of DCs could be used to monitor the release of these mediators into the perfusate.</p><p><strong>Methods: </strong>Human monocytes from buffy coats were differentiated into monocyte-derived DCs (moDCs). Perfusate was obtained from human donor kidneys deemed unsuitable for transplantation (n = 15) that underwent 6 h of NMP. MoDCs were incubated for 24 h with perfusate collected at different timepoints. DC supernatant was analyzed with Luminex and ELISA. MoDCs were analyzed with flow cytometry for maturation markers and co-cultured with allogenic T cells.</p><p><strong>Results: </strong>Incubation with perfusate resulted in moDCs with a reduced surface expression of CD86, without affecting other maturation markers. Analysis of DC supernatant showed there was a specific increase of IL-10 production upon incubation with perfusate. As a consequence, moDCs incubated with perfusate showed lower T cell stimulatory capacity.</p><p><strong>Conclusion: </strong>This study showed that the activation status of DCs can be used to monitor the release of factors into the perfusate during NMP with an anti-inflammatory DC phenotype and function. It demonstrates the feasibility of a cell-based model to determine immune regulatory effects during ex vivo organ perfusion.</p>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellen E Garven, Ethan Kung, Randy M Stevens, Christopher B Rodell, Amy L Throckmorton
{"title":"Multiscale Modeling of a Geometrically Tunable Shunt for Growing Pediatric Patients With Single Ventricle Physiology.","authors":"Ellen E Garven, Ethan Kung, Randy M Stevens, Christopher B Rodell, Amy L Throckmorton","doi":"10.1111/aor.70244","DOIUrl":"https://doi.org/10.1111/aor.70244","url":null,"abstract":"<p><strong>Background: </strong>Univentricular circulations are initially established with the placement of a fixed-diameter blood shunt to facilitate physiologic stability during growth. This fixed-diameter shunt (FDS) is geometrically static in a dynamically growth-driven environment. The neonatal cardiovascular hemodynamics are sensitive to the presence of the FDS and its fluidic and resistive properties, which creates significant interdependency and mortality risks. Thus, we have developed a geometrically tunable shunt to mitigate these hemodynamic challenges. Here, the tunable shunt is established by computational characterization of the hemodynamics over shunt usage in a patient specific anatomy.</p><p><strong>Methodology: </strong>Two multiscale cardiovascular models were implemented at time-points spanning across the beginning and end of the shunt-use period. These models were customized with patient-specific data from a clinical trial, drawing on observed geometric and fluidic conditions. A patient growth model between time-points was also established. For two patients, the tunable shunt was simulated across those time-points to identify the appropriate diameter changes that produced favorable hemodynamic conditions, per the pulmonary-to-systemic flow ratio (Q<sub>P</sub>/Q<sub>S</sub>).</p><p><strong>Results: </strong>Changes in vessel morphology, cardiac output, and vascular resistance were characterized and represented growth in the shunt-use period. Compared to the diameter at the beginning of the shunt-use period, a diameter expansion of 12%-13% was required at the end of the shunt-use period to balance the Q<sub>P</sub>/Q<sub>S</sub> for optimal blood oxygenation.</p><p><strong>Conclusion: </strong>These models are among the first to computationally study clinical time-points early in the post-operative univentricular patient. Using a complex model of growth, the tunable shunt design was investigated for its potential to alter and maintain hemodynamics over the growth months of infancy. These findings advanced the development of an innovative, tunable blood shunt for high-risk patients with complex congenital heart disease.</p>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Top-Down Hierarchical Allograft Engineering.","authors":"SunYoung Kim, Taufiek Konrad Rajab","doi":"10.1111/aor.70259","DOIUrl":"https://doi.org/10.1111/aor.70259","url":null,"abstract":"<p><strong>Background: </strong>More than 40 years of intensive research in tissue engineering have not produced clinically transplantable bioartificial organs. This limitation is intrinsic to the biological complexity of creating transplantable organs from the bottom-up using scaffolds seeded with stem cells. In contrast, allograft transplantation provides fully functional and architecturally organized organs at a level that no current bioengineering platform is even close to reproducing.</p><p><strong>Observations: </strong>This review defines the concept of allograft engineering: a top-down, allograft-centered paradigm that begins with the intact donor allograft and applies targeted bioengineering techniques to improve the suitability of the graft for transplantation. This makes allograft engineering across the following hierarchical levels possible: cellular modification to create chimeric grafts; molecular modification to alter the graft microenvironment; and genetic modification to reprogram graft gene expression.</p><p><strong>Conclusions: </strong>Clinical translation of this approach has the potential to transform the field of transplantation by delivering enhanced allografts that have increased availability, resistance to ischemia-reperfusion injury, and reduced immunogenicity.</p>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artificial organsPub Date : 2026-09-29Epub Date: 2026-06-07DOI: 10.1111/aor.70178
Benjamin Torner, Simon Klocker, Niccolò Crescenti, Aldo J. Suria, Harald Reithofer, Michael Hübler, Daniel Zimpfer, Marcus Granegger
{"title":"Shaping the Flow: Impact of Blade Shape on Performance and Hemocompatibility in Rotodynamic Blood Pumps","authors":"Benjamin Torner, Simon Klocker, Niccolò Crescenti, Aldo J. Suria, Harald Reithofer, Michael Hübler, Daniel Zimpfer, Marcus Granegger","doi":"10.1111/aor.70178","DOIUrl":"10.1111/aor.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Rotodynamic blood pumps (RBPs) must operate reliably across a wide range of clinical conditions, including off-design operating regimes. Although blade shape is known to influence off-design performance in conventional turbopumps, its impact on hydraulic performance and hemocompatibility in RBPs has not been systematically investigated. This study combines in silico and in vitro analyses to assess the effects of leading-edge geometry and blade thickness on performance (pressure head-flow rate characteristics, efficiencies) and hemocompatibility (damage index, DI) across multiple RBPs and operating conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three representative RBPs, a cavopulmonary assist device, the CentriMag RBP, and a novel ventricular assist device, were investigated. Semi-circular, elliptical, and wedge-shaped leading edges were implemented, whereas three blade thickness configurations were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Variations in leading-edge geometry resulted in minor differences in performance (< 3 percent in efficiency) and hemocompatibility (< 3% DI) across all devices and operating conditions. In contrast, blade thickness had a pronounced effect on performance under overload off-design operation, with thinner blades improving efficiency by up to 22%, while exhibiting only limited changes in hemocompatibility-related metrics (< 7% DI). The observed efficiency differences were primarily attributed to decreased friction losses caused by less channel blockage with thinner impeller blades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, impeller blade shape plays a secondary role in hemocompatibility within the investigated pump types and operating conditions. This finding suggests that leading-edge optimization may be deprioritized relative to other hemocompatibility-critical geometry parameters in RBP design. Blade thickness, however, may lead to unfavorable channel blockage effects and therefore needs to be optimized with respect to manufacturing constraints and hydraulic performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":"50 10","pages":"1360-1371"},"PeriodicalIF":2.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aor.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artificial organsPub Date : 2026-09-29Epub Date: 2026-08-25DOI: 10.1111/aor.70226
Hristian Hinkov, Sara Yousefzada, Isabell A. Just, Christoph Klein, Evgenij Potapov, Santiago Garcia, Dhairya Patel, Lauren S. Ranard, Arseniy Goncharov, Dean J. Kereiakes, Raj R. Makkar, Torsten P. Vahl, Tanja K. Rudolph, Axel Unbehaun
{"title":"Early Multicenter Outcomes of Dedicated Transcatheter Aortic Valve Replacement for Left Ventricular Assist Device-Associated Pure Aortic Regurgitation","authors":"Hristian Hinkov, Sara Yousefzada, Isabell A. Just, Christoph Klein, Evgenij Potapov, Santiago Garcia, Dhairya Patel, Lauren S. Ranard, Arseniy Goncharov, Dean J. Kereiakes, Raj R. Makkar, Torsten P. Vahl, Tanja K. Rudolph, Axel Unbehaun","doi":"10.1111/aor.70226","DOIUrl":"10.1111/aor.70226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aortic regurgitation (AR) is a frequent and clinically relevant complication in patients with left ventricular assist devices (LVAD), impairing circulatory support and worsening outcomes. Surgical aortic valve replacement often carries prohibitive risk in this population, while conventional transcatheter aortic valve replacement (TAVR) is limited by the lack of annular calcification. The JenaValve Trilogy is the first transfemoral TAVR system with regulatory approval for AR. Evidence on its use in LVAD patients remains scarce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective multicenter registry of LVAD recipients undergoing JenaValve Trilogy implantation for pure AR between 2020 and 2026 at five high-volume centers in Germany and the United States. Patient characteristics, procedural details, and outcomes were analyzed. The primary endpoint was device success according to Valve Academic Research Consortium-3 (VARC-3) criteria at 30 days. Secondary endpoints included peri-procedural complications, mortality, and device-related reinterventions at follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty patients (median age 66 years, 36.7% female, median LVAD support time: four years) were included. One patient did not meet criteria for technical success, and one experienced a fatal hemorrhagic stroke on postoperative day 2, rendering device success 93.3% (28/30). 30-day mortality was 3.3% (1/30). At a median follow-up of 273 days (IQR 30–491), survival was 93.3% (28/30).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This first multicenter experience demonstrates that JenaValve Trilogy provides a feasible and safe treatment option for clinically significant AR in LVAD patients at prohibitive surgical risk, with high device success and favorable short-term outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":"50 10","pages":"1427-1433"},"PeriodicalIF":2.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aor.70226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artificial organsPub Date : 2026-09-29Epub Date: 2026-07-09DOI: 10.1111/aor.70188
Dustin M. Anderson-Bell, Morgan M. Millar, Rachel R. Codden, Stavros Drakos, Craig Selzman, Chloe R. Skidmore, Margaret Carlson, Frederick Welt, Tom Hanff, Hiroshi Kagawa, Jason Glotzbach, Andrea Steely, Vikas Sharma, Matt Goodwin, Daniel Haase, Jason Carr, Joseph E. Tonna
{"title":"National Practice Patterns of VA ECMO and Left Ventricular Mechanical Unloading for Cardiogenic Shock","authors":"Dustin M. Anderson-Bell, Morgan M. Millar, Rachel R. Codden, Stavros Drakos, Craig Selzman, Chloe R. Skidmore, Margaret Carlson, Frederick Welt, Tom Hanff, Hiroshi Kagawa, Jason Glotzbach, Andrea Steely, Vikas Sharma, Matt Goodwin, Daniel Haase, Jason Carr, Joseph E. Tonna","doi":"10.1111/aor.70188","DOIUrl":"10.1111/aor.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiogenic shock (CS) remains highly morbid despite significant advancements in management. A cornerstone of this management is Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO). However, consensus surrounding the management of VA ECMO for CS, including the use of concomitant Left Ventricular Mechanical Unloading (LVMU), remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We thus conducted a national survey of practice patterns in the treatment of CS to characterize such variability. Surveys were distributed to physicians involved in management of VA ECMO across a variety of center types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Responses representing 67 institutions were analyzed. VA ECMO was used for a median of 10% of CS patients at each institution. Formal shock teams were present at 64.1% of centers and were associated with both higher annual VA ECMO volume (P⟨0.01) and greater intra-aortic balloon pump use prior to VA ECMO (<i>p</i> = 0.03). LVMU was employed by 63.4% of centers, most commonly using Impella (93.3%), with unloading initiated at ECMO cannulation in a median of 30% of cases. Triggers and targets for LVMU varied widely, though pulmonary capillary wedge pressure was the most common endpoint.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight substantial heterogeneity in CS diagnosis, VA ECMO initiation, and LVMU strategies, underscoring the need for prospective studies to define optimal care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":"50 10","pages":"1443-1452"},"PeriodicalIF":2.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artificial organsPub Date : 2026-09-29Epub Date: 2026-07-27DOI: 10.1111/aor.70197
Kilian A. Walter, Leonard Boerger, Anna Pietsch, Linda Gilles, Phillip Brunnbauer, Can Kamali, Karl H. Hillebrandt, Jasper Iske, Johann Pratschke, Igor M. Sauer, Nathanael Raschzok, Felix Krenzien, Simon Moosburner
{"title":"Nicotinamide Adenine Dinucleotide as a Potential Biomarker for Graft Viability During Normothermic Machine Perfusion: An Ex Vivo Rodent Study","authors":"Kilian A. Walter, Leonard Boerger, Anna Pietsch, Linda Gilles, Phillip Brunnbauer, Can Kamali, Karl H. Hillebrandt, Jasper Iske, Johann Pratschke, Igor M. Sauer, Nathanael Raschzok, Felix Krenzien, Simon Moosburner","doi":"10.1111/aor.70197","DOIUrl":"10.1111/aor.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The shortage of donor organs has increased the use of extended criteria donor (ECD) grafts in liver transplantation. Normothermic machine perfusion (NMP) could be used as a platform for real-time quality assessment, which is crucial since ECD grafts are more susceptible to ischemia–reperfusion injury (IRI). As nicotinamide adenine dinucleotide (NAD<sup>+</sup>) is a central mediator of cellular antioxidativedefense, reduced intracellular NAD (iNAD<sup>+</sup>) levels in grafts sustaining greater injury may reflect diminished antioxidative capacity and could serve as a marker to assess graft quality. This study aimed to investigate iNAD<sup>+</sup> in comparison to existing damage-associated parameters for liver graft quality in a small animal NMP model simulating ECD conditions through advanced donor age, prolonged cold ischemia time (CIT), and donation after circulatory death (DCD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-nine male Sprague–Dawley rat livers were analyzed across six experimental groups defined by donor age (3 months [young] or 12 months [elderly]), procurement modality (standard procurement or donation after circulatory death [DCD]), and cold ischemia time (CIT; 6 h or 12 h), followed by 6 h of NMP. No livers were excluded from analysis. iNAD<sup>+</sup> levels were quantified using a colorimetric enzymatic assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Perfusate iNAD<sup>+</sup> levels continuously rose over time during NMP and differed significantly between intervention groups (<i>p</i> = 0.003). iNAD+ correlated negatively with ALT levels (R = −0.36, <i>p</i> = 0.024) and liver tissue necrosis in grafts (perfusate R = −0.24, <i>p</i> = 0.17; tissue R = −0.19, <i>p</i> = 0.2), although these associations did not reach statistical significance. Long CIT, higher donor age, and DCD procurement were associated with lower iNAD+ levels. iNAD+ did not correlate with lactate clearance or bile production (both <i>p</i> > 0.05). A non-significant trend toward a positive association between iNAD+ and glucose metabolism was observed (<i>R</i> = 0.29, <i>p</i> = 0.077).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Higher perfusate iNAD+ levels were associated with better organ performance, consistent with iNAD+ reflecting the graft's antioxidative metabolic capacity. Lower iNAD+ levels in elderly and DCD grafts aligned with established damage markers. Perfusate iNAD+ may therefore offer a complementary tool for evaluating metabolic activity and organ performance during NMP, pending prospective validation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8450,"journal":{"name":"Artificial organs","volume":"50 10","pages":"1384-1395"},"PeriodicalIF":2.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}