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• W3047217279 abstract "Central MessageExtending perfusion times in ex vivo techniques.See Article page 1963. Extending perfusion times in ex vivo techniques. See Article page 1963. Extracorporeal lung perfusion may be used to improve metabolic support, extend perfusion times, and potentially optimize organ repair. Hozain and colleagues1Hozain A.E. O'Neill J.D. Pinezich M.R. Tipograf Y. Donocoff R. Cunningham K.M. et al.Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.Nat Med. 2020; 26: 1102-1113Crossref PubMed Scopus (25) Google Scholar recently reported improved perfusion times and enhanced lung recovery using a model of xenogeneic cross-circulation. Human lungs were, in this manner, perfused using swine circulation and regained function. Nevertheless, the findings highlight the metabolic and hormonal limitations of contemporary ex vivo techniques. They also demonstrate the need for improvements in organ support capabilities that will eliminate the need for xenogeneic cross-circulation. In this article, Takahashi and colleagues2Takahashi M. Cheung H. Watanabe T. Zamel R. Cypel M. Mingyao Liu M. et al.Strategies to prolong homeostasis of ex vivo perfused lungs.J Thorac Cardiovasc Surg. 2021; 161: 1963-1973Abstract Full Text Full Text PDF Scopus (11) Google Scholar catalog their use of modified ex vivo lung perfusate in a porcine model to achieve stable homeostasis in a bid to extend perfusion time. The contribution is timely and relevant and reflects the efforts of an experienced group of transplant surgeons. The authors used 4 groups of 5 Yorkshire male domestic pigs in keeping with the convention endorsed within previously published works.3Nakajima D. Watanabe Y. Ohsumi A. Pipkin M. Chen M. Mordant P. et al.Mesenchymal stromal cell therapy during ex vivo lung perfusion ameliorates ischemia-reperfusion injury in lung transplantation.J Heart Lung Transplant. 2019; 38: 1214-1223Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 4Koike T. Yeung J.C. Cypel M. Rubacha M. Matsuda Y. Sato M. et al.Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.J Heart Lung Transplant. 2011; 30: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 5Cypel M. Yeung J.C. Hirayama S. Rubacha M. Fischer S. Anraku M. et al.Technique for prolonged normothermic ex vivo lung perfusion.J Heart Lung Transplant. 2008; 27: 1319-1325Abstract Full Text Full Text PDF PubMed Scopus (352) Google Scholar, 6Yeung J.C. Cypel M. Machuca T.N. Koike T. Cook D.J. Bonato R. et al.Physiologic assessment of the ex vivo donor 406 lung for transplantation.J Heart Lung Transplant. 2012; 31: 1120-1126Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar However, the small sample size engenders the threat of a type 2 error that remains prevalent throughout the article. The authors used a mixed-effects linear regression and predicated the analysis on alterations in dynamic compliance and airway pressure. They selected, somewhat arbitrarily, the value of 15 mL/cm H2O as a cutoff for futility with a rationale that caters perhaps more to convenience than strict pathophysiologic construct. For this determination, the authors refer to previously published works in which they investigated the kinetics of lactate metabolism, highlighting the fact that lungs with high lactate/pyruvate ratios demonstrated higher peak airway pressures, lower glucose levels, and higher lactate levels.4Koike T. Yeung J.C. Cypel M. Rubacha M. Matsuda Y. Sato M. et al.Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.J Heart Lung Transplant. 2011; 30: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar There was a significant increase in dynamic compliance in the treatment groups, together with reductions in peak airway pressure and pulmonary vascular resistance, the latter of which distinguishes it from previous reports.7Buchko M.T. Stewart C.J. Hatami S. Himmat S. Freed D.H. Nagendran J. Total parenteral nutrition in ex vivo lung perfusion: addressing metabolism improves both inflammation and oxygenation.Am J Transplant. 2019; 19: 3390-3397Crossref PubMed Scopus (10) Google Scholar Nevertheless, multiple questions abound. How best can one interpret the observations, considering the use of lungs that had no significant inflammatory injury? Could the difference potentially be the result of a type 1 error? By their own admission, the authors admit this effect to be an incompletely understood phenomenon, and so it remains unclear how nutritional augmentation contributes to lung preservation. Unmitigated, the ambiguity tempers the enthusiasm and confidence with which the study is received. Furthermore, despite the decrease in cytokine levels within the small sample, it remains unclear which circulating biomarkers best reflect airway inflammation and lung function. As a result, authoritative conclusions must be attenuated somewhat. Nevertheless, the total parenteral nutrition group achieved significantly longer stable perfusion times. Likewise, inflammatory cytokine production was also notably reduced in the continuous replacement group. Having achieved intravascular delivery of mesenchymal stem cells during ex vivo lung perfusion in an earlier exploration, establishing homeostasis that might extend the duration of perfusion is truly of considerable clinical importance. Success in this regard may pave the way for the routine use of augmenting mediators in ex vivo perfusion. The rationale, nonetheless, remains equivocal in structure, process, and outcome but serves as fertile substrate to generate hypotheses and broaden the search for even more ways to extend perfusion in a quest, ultimately to increase the number of available organs for donation—the ultimate gift. Strategies to prolong homeostasis of ex vivo perfused lungsThe Journal of Thoracic and Cardiovascular SurgeryVol. 161Issue 6PreviewEx vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto ex vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A longer ex vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic ex vivo lung perfusion. 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