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dc.contributor.authorCowan, Douglas B.en_US
dc.contributor.authorYao, Rouanen_US
dc.contributor.authorAkurathi, Vamsidharen_US
dc.contributor.authorSnay, Erin R.en_US
dc.contributor.authorThedsanamoorthy, Jerusha K.en_US
dc.contributor.authorZurakowski, Daviden_US
dc.contributor.authorEricsson, Mariaen_US
dc.contributor.authorFriehs, Ingeborgen_US
dc.contributor.authorWu, Yaotangen_US
dc.contributor.authorLevitsky, Sidneyen_US
dc.contributor.authordel Nido, Pedro J.en_US
dc.contributor.authorPackard, Alan B.en_US
dc.contributor.authorMcCully, James D.en_US
dc.date.accessioned2016-10-11T20:25:55Z
dc.date.issued2016en_US
dc.identifier.citationCowan, D. B., R. Yao, V. Akurathi, E. R. Snay, J. K. Thedsanamoorthy, D. Zurakowski, M. Ericsson, et al. 2016. “Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection.” PLoS ONE 11 (8): e0160889. doi:10.1371/journal.pone.0160889. http://dx.doi.org/10.1371/journal.pone.0160889.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29002423
dc.description.abstractWe have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid integration and widespread distribution throughout the heart and provided cardioprotection from ischemia-reperfusion injury.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0160889en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976938/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectBiochemistryen
dc.subjectBioenergeticsen
dc.subjectEnergy-Producing Organellesen
dc.subjectMitochondriaen
dc.subjectCell Biologyen
dc.subjectCellular Structures and Organellesen
dc.subjectAnatomyen
dc.subjectCardiovascular Anatomyen
dc.subjectHearten
dc.subjectMedicine and Health Sciencesen
dc.subjectDiagnostic Medicineen
dc.subjectDiagnostic Radiologyen
dc.subjectMagnetic Resonance Imagingen
dc.subjectImaging Techniquesen
dc.subjectRadiology and Imagingen
dc.subjectNeuroimagingen
dc.subjectPositron Emission Tomographyen
dc.subjectNeuroscienceen
dc.subjectTomographyen
dc.subjectCritical Care and Emergency Medicineen
dc.subjectReperfusionen
dc.subjectSurgical and Invasive Medical Proceduresen
dc.subjectCardiovascular Proceduresen
dc.subjectCardiac Transplantationen
dc.subjectTransplantationen
dc.subjectOrgan Transplantationen
dc.subjectVascular Medicineen
dc.subjectIschemiaen
dc.subjectModel Organismsen
dc.subjectAnimal Modelsen
dc.subjectRabbitsen
dc.subjectOrganismsen
dc.subjectAnimalsen
dc.subjectVertebratesen
dc.subjectAmniotesen
dc.subjectMammalsen
dc.titleIntracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotectionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorCowan, Douglas B.en_US
dc.date.available2016-10-11T20:25:55Z
dc.identifier.doi10.1371/journal.pone.0160889*
dash.authorsorderedfalse
dash.contributor.affiliatedFriehs, Ingeborg
dash.contributor.affiliatedAkurathi, Vamsidhar
dash.contributor.affiliatedPackard, Alan
dash.contributor.affiliatedWu, Yaotang
dash.contributor.affiliatedMcCully, James
dash.contributor.affiliatedEricsson, Maria
dash.contributor.affiliatedCowan, Douglas
dash.contributor.affiliatedLevitsky, Sidney
dash.contributor.affiliatedZurakowski, David
dash.contributor.affiliatedDel Nido, Pedro


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