{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:14:06Z","timestamp":1760112846597,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia","award":["752\/UN4.22.\/PT.02.00\/2021"],"award-info":[{"award-number":["752\/UN4.22.\/PT.02.00\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: The main problem of vascular preservation is the maintenance of vessel graft quality and function following extended storage. Conventional preservation solutions such as histidine\u2013tryptophan\u2013ketoglutarate (HTK) solution, Phosphate-Buffer Solution (PBS), or sodium chloride 0.9% has been shown to be inadequate in preserving vascular physiological function after 3 days of cold storage. This study aimed to evaluate whether adenosine and lidocaine (AL) in a modified Krebs\u2013Henseleit (KH) solution can preserve the function and histological structure of rat aortic rings after 6 days. Materials and Methods: Thirty-five aortic rings from male Wistar rats (200\u2013300 g) were harvested and immediately immersed in one of the assigned cold preservation solutions: standard KH, modified KH (mod KH) with lower calcium (Ca2+) and higher magnesium content (Mg2+) with or without adenosine and lidocaine (mod KH-AL), and modified KH with AL, insulin, and melatonin (Mod KH-ALMI). The contraction and relaxation function of the aortic rings were examined using an isometric force transducer after 6 days of cold preservation. Hematoxylin and eosin staining were used to analyze the rings\u2019 histological structure. Results: Vascular contraction and relaxation functions were severely affected after a 6-day cold storage period in standard KH. Modifying the KH solution by reducing the Ca2+ and increasing the Mg2+ levels greatly recovered the vessel functions. The addition of AL or ALMI to the modified KH did not further recover vascular contractility. However, only the addition of AL to the modified KH increased the ACh-induced relaxation at 6 days when compared to the conventional KH, suggesting that endothelium preservation is improved. From histological analysis, it was found that the addition of AL but not ALMI further improved the endothelial lining and the structure of the elastic membrane layers of the preserved vessels after 6 days of cold preservation. Conclusions: The addition of AL to low calcium-high magnesium KH solution significantly enhanced endothelial preservation and improved endothelial-induced relaxation of preserved vessels after 6 days of cold storage.<\/jats:p>","DOI":"10.3390\/medicina60081284","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T07:59:07Z","timestamp":1723190347000},"page":"1284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low Calcium\u2013High Magnesium Krebs\u2013Henseleit Solution Combined with Adenosine and Lidocaine Improved Rat Aortic Function and Structure Following Cold Preservation"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-0599","authenticated-orcid":false,"given":"Aryadi","family":"Arsyad","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geni K. R.","family":"Lembang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sesilia L.","family":"Linda","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia Y.","family":"Djabir","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey P.","family":"Dobson","sequence":"additional","affiliation":[{"name":"Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mallis, P., Kostakis, A., Stavropoulos-Giokas, C., and Michalopoulos, E. (2020). Future perspectives in small-diameter vascular graft engineering. Bioengineering, 7.","DOI":"10.3390\/bioengineering7040160"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.xjtc.2020.10.042","article-title":"The radial artery: An important component of multiarterial coronary surgery and considerations for its optimal harvest","volume":"5","author":"Tatoulis","year":"2020","journal-title":"JTCVS Tech."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Amini, M., Hisdal, J., Rosales, A., Kalvoy, H., and Martinsen, O.G. (2019, January 9\u201314). Evaluating the Effects of Cold Storage on Vascular Grafts Using Bioimpedance Measurement Techniques. Proceedings of the 17th International Conference on Electrical Bioimpedance, Joinville, Santa Catarina, Brazil.","DOI":"10.1007\/978-981-13-3498-6_19"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jvs.2010.10.093","article-title":"Preservation of human artery function following prolonged cold storage with a new solution","volume":"53","author":"Garbe","year":"2011","journal-title":"J. Vasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/ejcts\/ezaa386","article-title":"Increased receptor expression supports vascular reactivity of the rabbit aorta during preservation","volume":"59","author":"Cupitra","year":"2020","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ostrozka-Cieslik, A. (2022). The Effect of Antioxidant Added to Preservation Solution on the Protection of Kidneys before Transplantation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063141"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1177\/0963689719872699","article-title":"Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms","volume":"28","author":"Chen","year":"2019","journal-title":"Cell Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000499610","article-title":"Organ Preservation into the 2020s: The Era of Dynamic Intervention","volume":"46","author":"Petrenko","year":"2019","journal-title":"Transfus. Med. Hemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1111\/bph.13517","article-title":"Targeting vascular (endothelial) dysfunction","volume":"174","author":"Daiber","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","first-page":"811","article-title":"Even short-time storage in physiological saline solution impairs endothelial vascular function of saphenous vein grafts","volume":"40","author":"Wilbring","year":"2011","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s40256-019-00345-5","article-title":"Adenosine and the Cardiovascular System","volume":"19","author":"Reiss","year":"2019","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dobson, G.P., Arsyad, A., and Letson, H.L. (2017). The adenosine hypothesis revisited: Modulation of coupling between myocardial perfusion and arterial compliance. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00824"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Arsyad, A., and Dobson, G.P. (2016). Lidocaine relaxation in isolated rat aortic rings is enhanced by endothelial removal: Possible role of Kv, K ATP channels and A2a receptor crosstalk. BMC Anesthesiol., 16.","DOI":"10.1186\/s12871-016-0286-y"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1213\/01.ANE.0000073162.27208.E9","article-title":"Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells","volume":"97","author":"Buckingham","year":"2003","journal-title":"Anesth. Analg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1213\/ANE.0000000000002102","article-title":"Lidocaine Prevents Oxidative Stress-Induced Endothelial Dysfunction of the Systemic Artery in Rats with Intermittent Periodontal Inflammation","volume":"124","author":"Saito","year":"2017","journal-title":"Anesth. Analg."},{"key":"ref_16","first-page":"203","article-title":"Effects of lidocaine on membrane stabilization in harvested vein graft storage","volume":"30","author":"Unal","year":"2009","journal-title":"Saudi Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.jtcvs.2011.06.045","article-title":"The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components","volume":"143","author":"Shi","year":"2012","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_18","first-page":"1841","article-title":"Adenosine and lidocaine (AL) combination dilates intimally damaged rat thoracic aortic rings and guinea pig mesenteric arteries: Possible significance to cardiac surgery","volume":"10","author":"Arsyad","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.ajem.2013.05.044","article-title":"Hemodynamic rescue and ECG stability during chest compressions using adenosine and lidocaine after 8-minute asphyxial hypoxia in the rat","volume":"31","author":"Djabir","year":"2013","journal-title":"Am. J. Emerg. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.jtcvs.2011.05.023","article-title":"Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: Toward therapeutic suspended animation","volume":"142","author":"Rudd","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_21","first-page":"1141","article-title":"Interactions of the pineal hormone melatonin with oxygen-centered free radicals: A brief review","volume":"26","author":"Reiter","year":"1993","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1385\/CBB:34:2:237","article-title":"Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: A review of the evidence","volume":"34","author":"Reiter","year":"2001","journal-title":"Cell Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2131\/jts.48.169","article-title":"Both osmolality-dependent and independent mechanisms are associated with acute hyperglycemia-induced cardiovascular adverse reactions: Analysis of the mutual interactions leading to cardiovascular phenotypes in dogs","volume":"48","author":"Kambayashi","year":"2023","journal-title":"J. Toxicol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/TP.0000000000003141","article-title":"Structure and Function of Porcine Arteries Are Preserved for up to 6 Days Using the HypoRP Cold-storage Solution","volume":"104","author":"Dreau","year":"2020","journal-title":"Transplant"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Arsyad, A., and Dobson, G.P. (2016). Adenosine relaxation in isolated rat aortic rings and possible roles of smooth muscle Kv channels, KATP channels and A2a receptors. BMC Pharmacol. Toxicol., 17.","DOI":"10.1186\/s40360-016-0067-8"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e20180048","DOI":"10.1590\/1678-7757-2018-0048","article-title":"The role of potassium channels in the endothelial dysfunction induced by periodontitis","volume":"26","author":"Olchanheski","year":"2018","journal-title":"J. Appl. Oral. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Luk, C., Haywood, N.J., Bridge, K.I., and Kearney, M.T. (2022). Paracrine role of the endothelium in metabolic homeostasis in health and nutrient excess. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.882923"},{"key":"ref_28","first-page":"107","article-title":"Recombinant human secretory leukocyte protease inhibitor ameliorated vessel preservation in experimentally isolated rat arteries","volume":"10","author":"Kongpol","year":"2020","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13241","DOI":"10.1111\/ctr.13241","article-title":"University of Wisconsin vs normal saline solutions for preservation of blood vessels of brain dead donors: A histopathological study","volume":"32","author":"Kazemi","year":"2018","journal-title":"Clin. Transpl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/icvts\/ivw056","article-title":"Graft preservation solutions in cardiovascular surgery","volume":"23","author":"Winkler","year":"2016","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1152\/ajpheart.01021.2020","article-title":"Guidelines for the measurement of vascular function and structure in isolated arteries and veins","volume":"321","author":"Wenceslau","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/0003-4975(95)00126-6","article-title":"Long-term preservation of vascular endothelium and smooth muscle","volume":"59","author":"Ingemansson","year":"1995","journal-title":"Ann. Thorac. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/S0003-4975(96)00897-1","article-title":"Addition of Calcium to Euro-Collins Solution Is Essential for 24-Hour Preservation of the Vasculature","volume":"63","author":"Ingemansson","year":"1997","journal-title":"Ann. Thorac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/0003-4975(95)01141-2","article-title":"Importance of calcium in long-term preservation of the vasculature","volume":"61","author":"Ingemansson","year":"1996","journal-title":"Ann. Thorac. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ceca.2011.03.003","article-title":"Calcium and cell death mechanisms: A perspective from the cell death community","volume":"50","author":"Zhivotovsky","year":"2011","journal-title":"Cell Calcium"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1139\/y87-120","article-title":"Mg2+\u2013Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels","volume":"65","author":"Altura","year":"1987","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0022-2828(86)80914-2","article-title":"Myocardial recovery during post-ischaemic reperfusion: Effects of nifedipine, calcium and magnesium","volume":"18","author":"Ferrari","year":"1986","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_38","first-page":"375","article-title":"Nitric oxide-dependent and-independent mechanisms account for gender differences in vasodilation to acetylcholine","volume":"292","author":"White","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.athoracsur.2016.05.097","article-title":"Intraoperative vein graft preservation: What is the solution?","volume":"102","author":"Woodward","year":"2016","journal-title":"Ann. Thorac. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.healun.2021.07.028","article-title":"Effects of graft preservation conditions on coronary endothelium and cardiac functional recovery in a rat model of donation after circulatory death","volume":"40","author":"Wyss","year":"2021","journal-title":"J. Heart Lung Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"L668","DOI":"10.1152\/ajplung.00198.2014","article-title":"Shear stress-related mechanosignaling with lung ischemia: Lessons from basic research can inform lung transplantation","volume":"307","author":"Chatterjee","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dobson, G.P., Morris, J.L., and Letson, H.L. (2023). Adenosine, lidocaine and Mg2+ update: Teaching old drugs new tricks. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1231759"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/s41467-017-00986-7","article-title":"Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation","volume":"8","author":"Xu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4097\/kjae.2010.59.2.104","article-title":"Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta","volume":"59","author":"Lee","year":"2010","journal-title":"Korean J. Anesthesiol."},{"key":"ref_45","first-page":"655","article-title":"Adenosine A2a receptors mediate coronary microvascular dilation to adenosine: Role of nitric oxide and atp-sensitive potassium channels","volume":"291","author":"Hein","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0306-3623(96)00517-4","article-title":"Effects of several class i antiarrhythmic drugs on isolated rat aortic vascular smooth muscle","volume":"29","author":"Tamargo","year":"1997","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ostrozka-Cieslik, A., and Dolinska, B. (2020). The Role of hormones and trophic factors as components of preservation solutions in protection of renal function before transplantation: A review of the literature. Molecules, 25.","DOI":"10.3390\/molecules25092185"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1530\/JOE-16-0117","article-title":"Potential benefits of melatonin in organ transplantation: A review","volume":"229","author":"Tan","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_49","first-page":"943","article-title":"Effect of melatonin on increasing the effectiveness of liver preservation solution","volume":"34","author":"Erdogan","year":"2023","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Korkmaz-Ic\u00f6z, S., Ballikaya, B., Soethoff, J., Kraft, P., Sayour, A.A., Radovits, T., Loganathan, S., Karck, M., Szab\u00f3, G., and Veres, G. (2021). Graft Preservation Solution DuraGraft\u00ae Alleviates Vascular Dysfunction Following In Vitro Ischemia\/Reperfusion Injury in Rats. Pharmaceuticals, 14.","DOI":"10.3390\/ph14101028"},{"key":"ref_51","first-page":"170","article-title":"Arterial graft preservation with an endothelial damage inhibitor reduces vascular dysfunction in a rat model of in vitro ischemia\/reperfusion injury","volume":"14","author":"Ballikaya","year":"2022","journal-title":"Arch. Cardiovasc. Dis. Suppl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1080\/14779072.2018.1532289","article-title":"Relationship between intra-operative vein graft treatment with DuraGraft\u00ae or saline and clinical outcomes after coronary artery bypass grafting","volume":"16","author":"Haime","year":"2018","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1080\/17434440.2019.1682996","article-title":"Intraoperative storage of saphenous vein grafts in coronary artery bypass grafting","volume":"16","author":"Pachuk","year":"2019","journal-title":"Expert. Rev. Med. Devices"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/8\/1284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:32:44Z","timestamp":1760110364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/8\/1284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["medicina60081284"],"URL":"https:\/\/doi.org\/10.3390\/medicina60081284","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2024,8,9]]}}}