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dc.contributor.authorWheeler, Thomas J.
dc.contributor.authorChien, Sufan
dc.contributor.editorMcNeil, Paul L.
dc.date.accessioned2012-10-26T16:40:50Z
dc.date.available2012-10-26T16:40:50Z
dc.date.issued2012-04-27en_US
dc.identifier.citationPLoS One. 2012 Apr 27; 7(4):e35023en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22558110en_US
dc.identifier.doi10.1371/journal.pone.0035023en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/708
dc.description.abstractEarlier studies by our group showed that fructose-1,6-bisphosphate (FBP) enhances the hypothermic preservation of rat cardiac myocytes and the functional recovery of animal hearts after hypothermic storage. However, the mechanisms involved were not clear. We extended the cardiomyocyte studies by testing whether the FBP effects were due to chelation of extracellular calcium, leading to lower intracellular levels. We also tested effects of 2,3-butanedione monoxime (BDM), pyruvate, and adenine nucleotide precursors. Cardiomyocytes were incubated in ischemic suspension at 3°C, and aliquots examined over 48 to 72 hours for retention of rod-shaped morphology, a measure of viability. Cytosolic Ca2+ levels were measured in some experiments. FBP at 5 mM reduced the death rate even when added after one or two days of incubation. It caused cytosolic calcium levels that were 33% lower than controls in freshly-isolated cells and 70% lower after one day of incubation. EGTA protected against cell death similarly to FBP. These results indicated that one of the mechanisms by which FBP exerts protective effects is through chelation of extracellular calcium. BDM was strongly protective and reduced cytosolic calcium by 30% after one day of incubation. As with FBP, BDM was effective when added after one or two days of incubation. BDM may be useful in combination with FBP in preserving heart tissue. Pyruvate, adenine, and ribose provided little or no protection during hypothermia.
dc.rightsWheeler, Chien. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectChemistryen_US
dc.subjectAnalytical Chemistryen_US
dc.subjectChemical Analysisen_US
dc.subjectQuantitative Analysisen_US
dc.subjectChemical Reactionsen_US
dc.subjectChelationen_US
dc.subjectMedicinal Chemistryen_US
dc.subjectMedicineen_US
dc.subjectCardiovascularen_US
dc.subjectCardiovascular Pharmacologyen_US
dc.subjectDrugs and Devicesen_US
dc.subjectCardiovascular Pharmacologyen_US
dc.subjectSurgeryen_US
dc.subjectTransplant Surgeryen_US
dc.subject.meshAdenineen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCalciumen_US
dc.subject.meshCell Survivalen_US
dc.subject.meshChelating Agentsen_US
dc.subject.meshCytosolen_US
dc.subject.meshDiacetylen_US
dc.subject.meshExtracellular Fluiden_US
dc.subject.meshFructose-Bisphosphataseen_US
dc.subject.meshMyocytes, Cardiacen_US
dc.subject.meshPyruvic Aciden_US
dc.subject.meshRatsen_US
dc.subject.meshRiboseen_US
dc.titleProtection of Rat Cardiac Myocytes by Fructose-1,6-Bisphosphate and 2,3-Butanedioneen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3338745en_US
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy
dc.contributor.corporatenameCollege of Graduate Studies
refterms.dateFOA2019-04-10T00:38:21Z
html.description.abstractEarlier studies by our group showed that fructose-1,6-bisphosphate (FBP) enhances the hypothermic preservation of rat cardiac myocytes and the functional recovery of animal hearts after hypothermic storage. However, the mechanisms involved were not clear. We extended the cardiomyocyte studies by testing whether the FBP effects were due to chelation of extracellular calcium, leading to lower intracellular levels. We also tested effects of 2,3-butanedione monoxime (BDM), pyruvate, and adenine nucleotide precursors. Cardiomyocytes were incubated in ischemic suspension at 3°C, and aliquots examined over 48 to 72 hours for retention of rod-shaped morphology, a measure of viability. Cytosolic Ca2+ levels were measured in some experiments. FBP at 5 mM reduced the death rate even when added after one or two days of incubation. It caused cytosolic calcium levels that were 33% lower than controls in freshly-isolated cells and 70% lower after one day of incubation. EGTA protected against cell death similarly to FBP. These results indicated that one of the mechanisms by which FBP exerts protective effects is through chelation of extracellular calcium. BDM was strongly protective and reduced cytosolic calcium by 30% after one day of incubation. As with FBP, BDM was effective when added after one or two days of incubation. BDM may be useful in combination with FBP in preserving heart tissue. Pyruvate, adenine, and ribose provided little or no protection during hypothermia.


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