Commentary: Making lungs great again—introducing new modifications to the Toronto ex vivo lung perfusion protocol

Central MessageNew strategies in ex vivo lung perfusion extend preservation to 24 hours—an achievement that will enable surgeons better allocate, evaluate, rehabilitate, and eventually enhance allografts.See Article page 1963. New allografts. See In clinical transplantation, (EVLP) offers 3 critical advantages over conventional methods. First, allografts, which reproducibly tolerate a limited time of cold storage, are reliably maintained with EVLP for 12 hours via the Toronto Protocol.1Cypel M. Yeung J.C. Liu Anraku Chen F. Karolak W. et al.Normothermic transplantation.N Engl J Med. 2011; 364: 1431-1440Crossref PubMed Scopus (726) Google Scholar,2Cypel Hirayama S. Rubacha Fischer al.Technique prolonged normothermic perfusion.J Heart Lung Transplant. 2008; 27: 1319-1325Abstract Full Text PDF (355) Scholar Second, provides an opportunity assess marginal organ performance before facilitating expansion ever-limited donor pool. Early outcomes using have been promising, initial experiences HELP1Cypel trial demonstrating equivalent survival INSPIRE (International Randomized Study TransMedics Organ Care System [OCS Lung] Preservation Transplantation)3Warnecke G. Van Raemdonck D. Smith M.A. Massard Kukreja J. Rea ex-vivo portable care system device bilateral transplantation (INSPIRE): randomised, open-label, non-inferiority, phase study.Lancet Respir 2018; 6: 357-367Abstract (100) identifying decreased rates early primary graft dysfunction patients receiving EVLP-preserved standard grafts. The NOVEL4Sanchez P. Davis R. D’Ovidio Cantu E. Weyant Camp al.The NOVEL one-year outcomes.J 2014; 33: S71-S72Abstract Scholar,5Sanchez D’ovidio Weyan as assessment lungs—the Trial.J 2013; 32: S16-S17Abstract EXPAND6Loor Warnecke Ardehali A. Moradiellos OCS EXPAND international interim results.J 2016; 35: S68-S69Abstract Scholar,7Loor Villavicencio al.Results (OCS) recruit evaluate extended criteria (ECD) lungs.J 37: S147Abstract trials subsequently affirmed utility when used Third most importantly, however, enormous potential improve both Notable preclinical approaches included gene therapy,8Machuca T.N. Cypel Bonato Chun Y.-M. Juvet al.Safety efficacy adenoviral IL-10 therapy large animal transplant model.Hum Gene Ther. 2017; 28: 757-765Crossref (66) Scholar, 9Cypel Sato McRae K. al.423: mediated interleukin 10 (AdhIL-10) 2007; 26: S212-S213Abstract 10Yeung Wagnetz Koike T. al.Ex vector delivery results vector-associated inflammation pre- post-lung pig.Mol 2012; 20: 1204-1211Abstract (76) novel drug delivery,11Lin H. Tian Tikkanen Ding L. Cheung H.Y.A. al.?1-Anti-trypsin improves function porcine lungs during 656-666Abstract (49) 12Martens Boada Vanaudenaerde B.M. Verleden S.E. Vos G.M. al.Steroids can reduce warm ischemic reperfusion injury donation after circulatory death model evaluation.Transplant Int. 29: 1237-1246Crossref (35) 13Mehaffey J.H. Charles E.J. Narahari A.K. Schubert Laubach V.E. Teman N.R. al.Increasing circulating sphingosine-1-phosphate attenuates Thorac Cardiovasc Surg. 156: 910-917Abstract (13) 14Burki Noda Philips B.J. Velayutham Shiva Sanchez P.G. al.Impact triptolide on grafts rat model.J January 23, 2020; ([Epub ahead print])PubMed hepatitis C virus inactivation,15Galasso Feld J.J. Watanabe Y. Pipkin Summers C. Ali al.Inactivating light therapies perfusion.Nat Commun. 2019; 10: 481Crossref (52) Scholar,16Cypel Galasso Ribeiro Wilson B. Bagnato V. Kurachi al.A evaluating effects ultra-violet treatment (UVC) method inactivating infection 38: S53-S54Abstract antibiosis,17Nakajima Machuca Iskender I. Hashimoto human lungs.Am 16: 1229-1237Crossref (96) stem cell therapy,18Nakajima Ohsumi Mordant al.Mesenchymal stromal ameliorates ischemia–reperfusion transplantation.J 1214-1223Abstract (30) thrombolytics19Machuca Hsin M.K. Ott H.C. Hwang D.M. al.Injury-specific lung: pulmonary thrombolysis followed by successful transplantation.Am Crit 188: 878-880Crossref (70) Scholar,20Inci Yamada Hillinger Jungraithmayr Trinkwitz Weder Successful reconditioning urokinase system.Ann 98: 1837-1838Abstract (41) optimize addition, anatomic interventions, including lavage aspiration injury21Nakajima Kalaf al.Lung surfactant replacement gastric acid aspiration–induced injury.J 36: 577-585Abstract bronchial artery perfusion,22Tanaka Isse Tobita Maniwa Bhama dual technique immediate experimental 2015; 15: 1219-1230Crossref (24) proposed transplant. Many these require beyond hours. One commonality among diverse is intention emulate complex homeostatic mechanisms present suddenly lost EVLP. Mechanisms regulating fluid electrolyte balance, metabolism nutrition, neuroendocrine regulation, immune responses all remain largely ignored preservation. Recently, principle establishing full physiologic support was elegantly described extracorporeal cross-circulation, 4 days23Hozain A.E. Tipograf Pinezich M.R. Cunningham K.M. Donocoff Queen al.Multiday maintenance cross-circulation conscious swine.J 159: 1640-1653.e18Abstract (22) repaired discarded xenogeneic model.24Hozain O’Neill J.D. al.Xenogeneic recovery injured lungs.Nat 1102-1113Crossref (26) Clinical application this approach, introduces new immunologic challenges recipients, well ethical considerations animals—or patients—who would serve “hosts.” As such, systems likely powerful tool years come despite current limitations. issue Journal, Takahashi colleagues25Takahashi Yu Zamel al.Strategies prolong homeostasis perfused 2021; 161: 1963-1973Abstract (12) demonstrate separate modifications Protocol This noteworthy clinicians continue investigate strength study includes straightforward adaptability their methods replacing and/or supplementing perfusate. These interventions also relatively inexpensive. authors glucose homeostasis, compared protocol. limitation were not transplanted viability; thorough histologic cytokine analysis suggests mitigated cellular injury. groups considered viable at hours, indicating although 24-hour now achievable, it yet fully reliable. Finally, experiments use acellular Steen Others shown perfusate may lead EVLP, so findings be universally applicable other systems.26Buchko M.T. Himmat Aboelnazar N.S. Stewart C.J. Hatami Dromparis A low-cost alternative perfusion. Transplant Proc. July 2, 2020Google Nonetheless, iterations refine practice bring us closer toward platform rehabilitation strategies. Strategies lungsThe Journal Thoracic Cardiovascular SurgeryVol. 161Issue 6PreviewEx innovative repair lungs. protocol preserve longer could more advanced rescue Our objective achieve stable Full-Text