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• W3115069093 abstract "Central MessageEx vivo heart perfusion is possible using continuous plasma exchange for a duration of 24 hours, potentially expanding time windows for evaluating candidate organs for heart transplantation.See Article page 128. Ex vivo heart perfusion is possible using continuous plasma exchange for a duration of 24 hours, potentially expanding time windows for evaluating candidate organs for heart transplantation. See Article page 128. Donor heart supply remains the fundamental limiter to heart transplantation. Despite a growing need for organs, only 1 in 3 hearts from organ donors are used for transplantation.1Khush K.K. Zaroff J.G. Nguyen J. Menza R. Goldstein B.A. National decline in donor heart utilization with regional variability: 1995-2010.Am J Transplant. 2015; 15: 642-649Crossref PubMed Scopus (113) Google Scholar To reduce the growing gap between organ supply versus need, expanded donor selection criteria, such as increased donor age and even donation after cardiac death, have emerged. The acceptance of more “marginal” donors must be balanced by the need to ensure appropriate organ quality. Furthermore, the 6-hour cold ischemic time window remains a geographic and logistical hurdle for transplantation. Ex vivo organ perfusion systems have promise to overcome these challenges. The TransMedics Organ Care System has been used in heart transplantation and shown to be safe with normothermic perfusion times of less than 4 hours.2Ardehali A. Esmailian F. Deng M. Soltesz E. Hsich E. Naka Y. et al.Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.Lancet. 2015; 385: 2577-2584Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar In this study, Tchouta and colleagues3Tchouta L. Drake D. Hoenerhoff M. Rojas-Pena A. Haft J. Owens G. et al.Twenty-four-hour normothermic perfusion of isolated ex vivo hearts using plasma exchange.J Thorac Cardiovasc Surg. 2022; 164: 128-138Abstract Full Text Full Text PDF Scopus (3) Google Scholar from the University of Michigan push the clock even further, demonstrating good explanted heart function 24 hours after explanation in pig hearts using normothermic ex vivo perfusion. This same group has previously demonstrated good heart function up to 3 days after explanation using a paracorporeal animal.4McLeod J.S. Poling C. Church J.T. Jung J. Sarosi E. Langley M. et al.Ex vivo heart perfusion for 72 hours using plasma cross circulation.ASAIO J. 2020; 66: 753-759Crossref PubMed Scopus (11) Google Scholar Informed by their previous work, Tchouta and colleagues engineered an ex vivo system that allows continuous exchange of donor plasma from the organ circulation with pooled porcine plasma. This continuous plasma exchange enables the removal of toxins while maintaining oncotic pressure and possibly other beneficial proteins found within plasma, similar to what might occur with a paracorporeal animal. Although this study represents an innovative step toward increasing the clinical utility of vivo organ perfusion systems, some important limitations remain. First, the impact of donor brain death upon the donor heart is not accounted for in this study yet is an important factor clinically. Brain death impairs donor heart function both in the donor and, potentially, in the recipient and activates apoptotic and inflammatory pathways.5Wilhelm M.J. Pratschke J. Laskowski I.A. Paz D.M. Tilney N.L. Brain death and its impact on the donor heart-lessons from animal models.J Heart Lung Transplant. 2000; 19: 414-418Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Second, ex vivo heart assessment was limited to the left ventricle and only at a fixed volume using a balloon transduction system. True left ventricle performance would be better assessed using pressure–volume analysis at different loading conditions.6Burkhoff D. Mirsky I. Suga H. Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers.Am J Physiol Heart Circ Physiol. 2005; 289: H501-H512Crossref PubMed Scopus (563) Google Scholar Furthermore, as the authors point out, cardiac functional assessment after a second cold ischemic insult and implantation was not assessed and thus unknown. Finally, the perfusate may have an important impact on heart inflammation and immune activation after transplantation. Although donor blood offers the obvious advantage of oxygen carrying red blood cells, donor immune cells could promote inflammation. The addition of pooled plasma from multiple donors may further amplify inflammation and merits further investigation. Further innovation and development of ex vivo heart perfusion is necessary to expand the availability of heart transplantation. By increasing the time window, surgeons can better assess more marginal hearts and potentially intervene using novel therapies, such as gene- and cell-based therapies to reduce ischemia–reperfusion injury and graft rejection.7Bishawi M. Roan J.N. Milano C.A. Daneshmand M.A. Schroder J.N. Chiang Y. et al.A normothermic ex vivo organ perfusion delivery method for cardiac transplantation gene therapy.Sci Rep. 2019; 9: 8029Crossref PubMed Scopus (31) Google Scholar Hearts that are currently being discarded may be found to be getting better with every beat and instead transplanted. As the authors describe, realization of this goal may one day make heart transplantation an “elective” procedure and more widely available to patients with advanced heart failure. Twenty-four-hour normothermic perfusion of isolated ex vivo hearts using plasma exchangeThe Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 1PreviewCross-circulation of plasma from a paracorporeal animal allows successful ex vivo heart perfusion (EVHP) for 3 days. Little is known about the feasibility of prolonged EVHP without a paracorporeal animal. These experiments evaluated plasma exchange (PX) that infuses fresh plasma, whereas an equal amount is removed to replace paracorporeal cross-circulation. Full-Text PDF" @default.
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• W3115069093 title "Commentary: Getting better with every beat. Extending the clock with ex vivo perfusion for heart transplantation" @default.
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