Commentary: Maintaining the pHysiological equilibrium

Central MessageAdaptions of current EVLP protocols are needed to be able perfuse donor lungs for 24 hours and longer.See Article page 1963. Adaptions longer. See A great potential ex vivo lung perfusion (EVLP) lies in reconditioning grafts an unacceptable quality so that they can used transplantation. In this regard, several approaches have been described experimental studies, including the treatment infected with high-dose antibiotics,1Nakajima D. Cypel M. Bonato R. Machuca T.N. Iskender I. Hashimoto K. et al.Ex infection human lungs.Am J Transplant. 2016; 16: 1229-1237Crossref PubMed Scopus (96) Google Scholar increasing endogenous interleukin-10 production by gene therapy,2Yeung J.C. Wagnetz Rubacha Koike T. Chun Y.-M. adenoviral vector delivery results decreased vector-associated inflammation pre- post-lung transplantation pig.Mol Ther. 2012; 20: 1204-1211Abstract Full Text PDF (76) clearing a graft from hepatitis C virus.3Galasso Feld J.J. Watanabe Y. Pipkin Summers C. Ali A. al.Inactivating virus using light therapies during normothermic perfusion.Nat Commun. 2019; 10: 481Crossref (52) However, clinical applicability most these is limited inability perfusing allograft prolonged period time. routine, 4- 6-hour run performed safely, which usually allows thorough assessment marginal organs; however, it often too short correct severe derangements allografts. article “Strategies Prolong Homeostasis Ex Vivo Perfused Lungs,” Takahashi colleagues4Takahashi Cheung H. Zamel Mingyao Liu al.Strategies prolong homeostasis perfused lungs.J Thorac Cardiovasc Surg. 2021; 161: 1963-1973Abstract (11) explored 3 different modifications Toronto protocol pig model hours: (1) continuous replacement perfusate, (2) adding glucose sodium maintain perfusate osmolality, (3) parenteral nutrition supplemented amino acids vitamins. The authors showed all resulted stable conditions hours, improved functional parameters grafts, reduced inflammatory burden. This paper highlights necessity develop more physiological safely times. particular, fact pH could maintained above 7.0 noteworthy. plays fundamental role physiology. During EVLPs, slow decrease observed, deteriorating faster decay pH.5Koike Yeung Matsuda Sato al.Kinetics lactate metabolism acellular perfusion.J Heart Lung 2011; 30: 1312-1319Abstract (49) An acidic destabilize proteins ultimately leads their denaturation, consequent destruction cell membranes apoptosis. low result increased anaerobic glycolysis accumulation.5Koike Scholar, 6Slama Barta Schillab L. Mitterbauer Jaksch P. Hoetzenecker al.Metabolic ex-vivo (EVLP): new decision making.J 2015; 34: S97Google 7Mazzeo A.T. Fanelli V. Boffini Medugno Filippini Simonato E. al.Feasibility microdialysis assess 38: 267-276Abstract (9) reasons remain elusive; mitochondrial dysfunction damaged seems likely.8Thelin E.P. Carpenter K.L.H. Hutchinson P.J. Helmy Microdialysis monitoring traumatic brain injury its neuroprotective drug development.AAPS J. 2017; 19: 367-376Crossref (24) Current do not consider acid–base compensatory or electrolyte-stabilizing mechanisms as physiologically provided kidney. Keshavjee colleagues chose substitute large volumes equilibrium. It tempting speculate whether addition hemodialysis membrane setup would lead similar allow long-time perfusion, maybe even beyond hours. conclusion, study Extended research group highly relevant represents next step toward 24-hour organ preservation. Strategies lungsThe Journal Thoracic Cardiovascular SurgeryVol. 161Issue 6PreviewEx provides innovative method repair lungs. reliably reproducibly preserve 12 longer preservation time enable application advanced rescue transplant. Our objective was achieve perfusion. Full-Text