{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:05:50Z","timestamp":1789995950565,"version":"4.0.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Extending donor organ preservation times would substantially improve patient outcomes by widening safety margins and enabling better donor-to-patient matching. While clinical 4\u00b0C static storage typically preserves donor kidneys for 18\u201324\u2005h, donor hearts are limited to \u223c4\u2005h. This clinical disparity is traditionally attributed to the higher baseline metabolic demand of cardiac tissue. This narrative review challenges this conventional assumption by comparing the distinct metabolic profiles of the heart and kidney at both 37\u00b0C and 4\u00b0C. We propose two mechanisms to explain how kidneys maintain robust functional recovery despite a much steeper decline in ATP concentration during hypothermic storage: (1) a significantly higher ATP consumption rate in hypothermic kidneys compared to hearts, and (2) a lower susceptibility to and degree of cold-induced tissue acidosis in the kidney. Building on these pathways, we outline targeted therapeutic interventions, such as inhibition of the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    -exchanger, to mitigate downstream sodium and calcium overload in cardiac tissue. Finally, we advance acidosis as a salient concern in organ cryopreservation, offering a fresh mechanistic framework (the acidosis hypothesis) to alleviate non-specific cryoprotective agent (CPA) toxicity and enhance heart tolerance during hypothermic CPA exposure.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1930065","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:20:17Z","timestamp":1789993217000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Learning from the kidney: improving heart recovery from hypothermia"],"prefix":"10.3389","volume":"13","author":[{"given":"Casey","family":"Kraft","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Bischof","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Department of Mechanical Engineering, University of Minnesota","place":["Minneapolis, MN, United States"]},{"name":"Institute for Engineering in Medicine, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik B.","family":"Finger","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.healun.2024.10.030","article-title":"Donor age and ischemic time in heart transplantaton, implications for organ preservation","volume":"44","author":"Jernryd","year":"2025","journal-title":"J Heart Lung Transplant"},{"key":"B2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1053\/j.semtcvs.2021.01.001","article-title":"Donor and recipient size matching in heart transplantation with predicted heart and lean body mass","volume":"34","author":"Miller","year":"2022","journal-title":"Semin Thorac Cardiovasc Surg"},{"key":"B3","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s00345-015-1679-0","article-title":"Nighttime kidney transplantation is associated with less pure technical graft failure","volume":"34","author":"Brunschot","year":"2016","journal-title":"World J Urol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/S0022-5223(98)00452-8","article-title":"Continuous perfusion of donor hearts in the beating state extends preservation time and improves recovery of function","volume":"116","author":"Hassanein","year":"1998","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e15296","DOI":"10.1111\/ctr.15296","article-title":"Financial impact of donation after circulatory death heart transplantation: a single-center analysis","volume":"38","author":"Urban","year":"2024","journal-title":"Clin Transplant"},{"key":"B6","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.xjon.2024.08.005","article-title":"Out of the ice age: preservation of cardiac allografts with a reusable 10\u2005\u00b0C cooler","volume":"21","author":"Trahanas","year":"2024","journal-title":"JTCVS Open"},{"key":"B7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.healun.2022.08.030","article-title":"Donor heart selection: evidence-based guidelines for providers","volume":"42","author":"Copeland","year":"2023","journal-title":"J Heart Lung Transplant"},{"key":"B8","year":"2026"},{"key":"B9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/S0022-5347(17)49779-5","article-title":"A flexible procedure for multiple cadaveric organ procurement","volume":"158","author":"Starzl","year":"1984","journal-title":"Surg Gynecol Obstet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1097\/00007890-199202010-00007","article-title":"Limitations of heart preservation by cold storage","volume":"53","author":"Stringham","year":"1992","journal-title":"Transplantation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1016\/S0041-1345(97)00441-7","article-title":"Calcium antagonists improve kidney function in the rat after cold storage in high-Na UW but not in high-K UW solution","volume":"29","author":"Hadj-A\u00efssa","year":"1997","journal-title":"Transplant Proc"},{"key":"B12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1017\/CBO9780511921896.015","article-title":"Fundamental aspects of vitrification as a method of reproductive cell, tissue, and organ cryopreservation","volume-title":"Principles and Practice of Fertility Preservation","author":"Mullen","year":"2011"},{"key":"B13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1097\/MOT.0000000000000534","article-title":"Cryopreservation by vitrification: a promising approach for transplant organ banking","volume":"23","author":"Finger","year":"2018","journal-title":"Curr Opin Organ Transplant"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1038\/s41467-023-38824-8","article-title":"Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model","volume":"14","author":"Han","year":"2023","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2100873","DOI":"10.1002\/admt.202100873","article-title":"Vitrification and rewarming of magnetic nanoparticle-loaded rat hearts","volume":"7","author":"Gao","year":"2022","journal-title":"Advanced Materials Technologies"},{"key":"B16","doi-asserted-by":"publisher","first-page":"104842","DOI":"10.1016\/j.cryobiol.2023.104842","article-title":"Cpa toxicity screening of cryoprotective solutions in rat hearts","volume":"114","author":"Kraft","year":"2024","journal-title":"Cryobiology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0142828","article-title":"Toxicity minimized cryoprotectant addition and removal procedures for adherent endothelial cells","volume":"10","author":"Davidson","year":"2015","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1089\/rej.2014.1656","article-title":"Cryoprotectant toxicity: facts, issues, and questions","volume":"18","author":"Best","year":"2015","journal-title":"Rejuvenation Res"},{"key":"B19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1201\/9781420004229.ch2","article-title":"Biology of cell survival in the cold: the basis for biopreservation of tissues and organs","volume-title":"Advances in Biopreservation","author":"Taylor","year":"2006"},{"key":"B20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cryobiol.2003.11.004","article-title":"Improved vitrification solutions based on the predictability of vitrification solution toxicity","volume":"48","author":"Fahy","year":"2004","journal-title":"Cryobiology"},{"key":"B21","first-page":"61","article-title":"Organ and tissue contribution to metabolic rate","volume-title":"Energy Metabolism: Tissue Determinants and Cellular Corollaries","author":"Elia","year":"1992"},{"key":"B22","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/0006-3002(50)90032-1","article-title":"Body size and tissue respiration","volume":"4","author":"Krebs","year":"1950","journal-title":"Biochim Biophys Acta"},{"key":"B23","doi-asserted-by":"publisher","first-page":"R415","DOI":"10.1152\/ajpregu.1985.248.4.R415","article-title":"Mammals: an allometric study of metabolism at tissue and mitochondrial level","volume":"248","author":"Else","year":"1985","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3390\/cells11010131","article-title":"Substrate- and calcium-dependent differential regulation of mitochondrial oxidative phosphorylation and energy production in the heart and kidney","volume":"11","author":"Zhang","year":"2022","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","first-page":"E943","DOI":"10.1152\/ajpendo.1992.262.6.E943","article-title":"Nmr-Invisible atp in heart: fact or fiction?","volume":"262","author":"Bak","year":"1992","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.bbrc.2009.10.067","article-title":"A subset of 26s proteasomes is activated at critically low atp concentrations and contributes to myocardial injury during cold ischemia","volume":"390","author":"Geng","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"B27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0011-2240(84)90017-8","article-title":"Stimulation of atp synthesis in hypothermically perfused dog kidneys by adenosine and Po4","volume":"21","author":"Southard","year":"1984","journal-title":"Cryobiology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1172\/JCI111718","article-title":"Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart","volume":"75","author":"Weiss","year":"1985","journal-title":"J Clin Invest"},{"key":"B29","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/s41467-021-21301-5","article-title":"Renal metabolism and hypertension","volume":"12","author":"Tian","year":"2021","journal-title":"Nat Commun"},{"key":"B30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1177\/000456327801500111","article-title":"The origin of the acidosis in hyperlactataemia","volume":"15","author":"Zilva","year":"1978","journal-title":"Ann Clin Biochem"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/s12276-022-00802-3","article-title":"Tracing the lactate shuttle to the mitochondrial Reticulum","volume":"54","author":"Brooks","year":"2022","journal-title":"Exp Mol Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1172\/jci105375","article-title":"Renal gluconeogenesis in acidosis, alkalosis, and potassium deficiency: its possible role in regulation of renal ammonia production","volume":"45","author":"Goodman","year":"1966","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1172\/JCI106016","article-title":"Liver and kidney metabolism during prolonged starvation","volume":"48","author":"Owen","year":"1969","journal-title":"J Clin Invest"},{"key":"B34","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/0026-0495(72)90028-5","article-title":"Gluconeogenesis","volume":"21","author":"Exton","year":"1972","journal-title":"Metab Clin Exp"},{"key":"B35","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/0011-2240(83)90029-9","article-title":"Comparison of the effect of temperature on kidney Cortex mitochondria from rabbit, dog, pig, and human: arrhenius plots of adp-stimulated respiration","volume":"20","author":"Southard","year":"1983","journal-title":"Cryobiology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0014-5793(86)81204-2","article-title":"31p Nmr measurement of atp synthesis rate in perfused intact rat hearts","volume":"198","author":"Kingsley-Hickman","year":"1986","journal-title":"FEBS Lett"},{"key":"B37","doi-asserted-by":"publisher","first-page":"F158","DOI":"10.1152\/ajprenal.1984.247.1.F158","article-title":"Quantitation of [3h]ouabain binding and turnover of Na-K-atpase along the rabbit nephron","volume":"247","author":"El Mernissi","year":"1984","journal-title":"Am J Physiol Renal Physiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"C731","DOI":"10.1152\/ajpcell.1987.253.5.C731","article-title":"Na-K pump site density and ouabain binding affinity in cultured chick heart cells","volume":"253","author":"Lobaugh","year":"1987","journal-title":"Am J Physiol Cell Physiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1085\/jgp.94.3.511","article-title":"Steady-State current-voltage relationship of the Na\/K pump in Guinea pig ventricular myocytes","volume":"94","author":"Gadsby","year":"1989","journal-title":"J Gen Physiol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/s0730-725x(00)00142-9","article-title":"Tissue Ph in human kidney transplants during hypothermic ischemia","volume":"18","author":"M\u00f6ller","year":"2000","journal-title":"Magn Reson Imaging"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5630","DOI":"10.1016\/S0021-9258(17)33104-6","article-title":"Phosphofructokinase. I. Mechanism of the Ph-dependent inactivation and reactivation of the rabbit muscle enzyme","volume":"251","author":"Bock","year":"1976","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1161\/01.RES.65.4.1045","article-title":"Role of intracellular Na+ in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of H+-Na+ and Na+-Ca2+ exchange","volume":"65","author":"Tani","year":"1989","journal-title":"Circ Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1161\/01.res.55.6.816","article-title":"Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts","volume":"55","author":"Neely","year":"1984","journal-title":"Circ Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"H1082","DOI":"10.1152\/ajpheart.1998.274.4.H1082","article-title":"Metabolic inhibition in the perfused rat heart: evidence for glycolytic requirement for normal sodium homeostasis","volume":"274","author":"Dizon","year":"1998","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B45","first-page":"H2145","article-title":"Attenuation of postischemic reperfusion injury is related to prevention of [Ca2+]m overload in rat hearts","volume-title":"Am J Physiol","author":"Miyamae","year":"1996"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.athoracsur.2007.10.054","article-title":"Sodium-Hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the expedition study","volume":"85","author":"Mentzer","year":"2008","journal-title":"Ann Thorac Surg"},{"key":"B47","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/s0008-6363(96)88579-8","article-title":"Protective effects of Hoe642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion","volume":"29","author":"Scholz","year":"1995","journal-title":"Cardiovasc Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3032","DOI":"10.1161\/01.CIR.102.25.3032","article-title":"Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations","volume":"102","author":"Th\u00e9roux","year":"2000","journal-title":"Circulation"},{"key":"B49","doi-asserted-by":"publisher","first-page":"284","DOI":"10.31083\/j.rcm2308284","article-title":"The remaining conundrum of the role of the Na(+)\/H(+) exchanger isoform 1 (Nhe1) in cardiac physiology and pathology: can it be rectified?","volume":"23","author":"Karmazyn","year":"2022","journal-title":"Rev Cardiovasc Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0022-3565(24)37573-1","article-title":"A new sodium\/hydrogen exchange inhibitor, emd 85131, limits infarct size in dogs when administered before or after coronary artery occlusion1","volume":"286","author":"Gumina","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"B51","doi-asserted-by":"publisher","first-page":"E1644","DOI":"10.1016\/S0735-1097(01)01608-4","article-title":"The Na+\/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction1","volume":"38","author":"Zeymer","year":"2001","journal-title":"JACC"},{"key":"B52","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0026-895X(25)14955-9","article-title":"Structure-Activity relationships of amiloride and certain of its analogues in relation to the blockade of the Na+\/H+ exchange system","volume":"25","author":"Vigne","year":"1984","journal-title":"Mol Pharmacol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/S1053-2498(01)00383-7","article-title":"Inhibition of Na+\/H+ isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage","volume":"21","author":"Stowe","year":"2002","journal-title":"J Heart Lung Transplant"},{"key":"B54","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/S1010-7940(02)00572-9","article-title":"The role of Na+\/H+ exchange in the efficacy of multidose hypothermic cardioplegia in immature rabbit hearts","volume":"22","author":"Murashita","year":"2002","journal-title":"Eur J Cardiothorac Surg"},{"key":"B55","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/BF01908058","article-title":"Myocardial lactate dehydrogenase isoenzyme distribution in the normal heart","volume":"76","author":"Schulthei\u00df","year":"1981","journal-title":"Basic Res Cardiol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/0003-9861(58)90374-6","article-title":"On the importance of being ionized","volume":"78","author":"Davis","year":"1958","journal-title":"Arch Biochem Biophys"},{"key":"B57","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jss.2019.04.041","article-title":"The effect of cardiac preservation solutions on heart transplant survival","volume":"242","author":"Carter","year":"2019","journal-title":"J Surg Res"},{"key":"B58","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/00007890-198701000-00002","article-title":"72-hour preservation of the canine pancreas","volume":"43","author":"Wahlberg","year":"1987","journal-title":"Transplantation"},{"key":"B59","doi-asserted-by":"publisher","first-page":"108895","DOI":"10.1016\/j.nucmedbio.2024.108895","article-title":"Evaluation of acute intravenous toxicity of hepes: is good\u2019s buffer good and safe enough for clinical utilization in nuclear medicine?","volume":"132","author":"Guleria","year":"2024","journal-title":"Nucl Med Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"103624","DOI":"10.1016\/j.isci.2021.103624","article-title":"Beat-to-Beat dynamic regulation of intracellular pH in cardiomyocytes","volume":"25","author":"Lyu","year":"2022","journal-title":"iScience"},{"key":"B61","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/0011-2240(84)90079-8","article-title":"Vitrification as an approach to cryopreservation","volume":"21","author":"Fahy","year":"1984","journal-title":"Cryobiology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.stemcr.2013.11.008","article-title":"Pgc-1alpha and reactive oxygen Species regulate human embryonic stem cell-derived cardiomyocyte function","volume":"1","author":"Birket","year":"2013","journal-title":"Stem Cell Rep"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1930065\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:20:19Z","timestamp":1789993219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1930065\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":62,"alternative-id":["10.3389\/fcvm.2026.1930065"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1930065","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]},"article-number":"1930065"}}