2023
Improvement in cardiac function and regional LV strain following intramyocardial injection of a theranostic hydrogel early postmyocardial infarction in a porcine model
Avendaño R, Midgett D, Melvinsdottir I, Thorn S, Uman S, Pickell Z, Lee S, Liu Z, Mamarian M, Duncan J, Spinale F, Burdick J, Sinusas A. Improvement in cardiac function and regional LV strain following intramyocardial injection of a theranostic hydrogel early postmyocardial infarction in a porcine model. Journal Of Applied Physiology 2023, 135: 405-420. PMID: 37318987, PMCID: PMC10538987, DOI: 10.1152/japplphysiol.00342.2022.Peer-Reviewed Original ResearchConceptsMyocardial infarctionIntramyocardial deliveryLV hemodynamicsControl groupFunctional indexEarly post-myocardial infarctionSystolic functional indicesMyocardial performance indexAnterolateral myocardial infarctionLeft anterior descendingPressure-volume loop areaLeft ventricular remodelingGlobal LV functionLV functional changesPost-myocardial infarctionSupply/demand ratioRegional LV strainHydrogel groupTei indexEjection fractionHeart failureAnterior descendingCircumflex arteryLV functionAortic pressure
2022
Quantification of intramyocardial blood volume using 99mTc-RBC SPECT/CT: a pilot human study
Yousefi H, Shi L, Soufer A, Tsatkin V, Bruni W, Avendano R, Greco K, McMahon D, Thorn S, Miller E, Sinusas A, Liu C. Quantification of intramyocardial blood volume using 99mTc-RBC SPECT/CT: a pilot human study. Journal Of Nuclear Cardiology 2022, 30: 292-297. PMID: 36319815, DOI: 10.1007/s12350-022-03123-0.Peer-Reviewed Original ResearchCellular recovery after prolonged warm ischaemia of the whole body
Andrijevic D, Vrselja Z, Lysyy T, Zhang S, Skarica M, Spajic A, Dellal D, Thorn SL, Duckrow RB, Ma S, Duy PQ, Isiktas AU, Liang D, Li M, Kim SK, Daniele SG, Banu K, Perincheri S, Menon MC, Huttner A, Sheth KN, Gobeske KT, Tietjen GT, Zaveri HP, Latham SR, Sinusas AJ, Sestan N. Cellular recovery after prolonged warm ischaemia of the whole body. Nature 2022, 608: 405-412. PMID: 35922506, PMCID: PMC9518831, DOI: 10.1038/s41586-022-05016-1.Peer-Reviewed Original ResearchConceptsSingle-nucleus transcriptomic analysesSpecific gene expression patternsCellular recoveryGene expression patternsCellular processesMammalian cellsTranscriptomic analysisLarge mammalsExpression patternsCellular repair processesCell deathComprehensive resourceUnderappreciated potentialPhysiological challengesTissue integrityRepair processSpecific changesPorcine brainMammalsOrgansMultiple organsMatrix Metalloproteinase-Targeted SPECT/CT Imaging for Evaluation of Therapeutic Hydrogels for the Early Modulation of Post-Infarct Myocardial Remodeling
Thorn SL, Shuman JA, Stacy MR, Purcell BP, Doviak H, Burdick JA, Spinale FG, Sinusas AJ. Matrix Metalloproteinase-Targeted SPECT/CT Imaging for Evaluation of Therapeutic Hydrogels for the Early Modulation of Post-Infarct Myocardial Remodeling. Journal Of Cardiovascular Translational Research 2022, 16: 155-165. PMID: 35697979, PMCID: PMC10836411, DOI: 10.1007/s12265-022-10280-7.Peer-Reviewed Original ResearchIncreasing angular sampling through deep learning for stationary cardiac SPECT image reconstruction
Xie H, Thorn S, Chen X, Zhou B, Liu H, Liu Z, Lee S, Wang G, Liu YH, Sinusas AJ, Liu C. Increasing angular sampling through deep learning for stationary cardiac SPECT image reconstruction. Journal Of Nuclear Cardiology 2022, 30: 86-100. PMID: 35508796, DOI: 10.1007/s12350-022-02972-z.Peer-Reviewed Original ResearchConceptsDeep learningReconstruction qualityImage reconstructionDeep learning methodsDeep neural networksDeep learning resultsImage qualityNetwork trainingSPECT image reconstructionNeural networkLearning methodsHigh image resolutionImage volumesClinical softwareImage metricsImage resolutionReconstruction resultsImproved image qualityTesting dataLearning resultsNetwork resultsPhysical phantomStationary imagingDifferent subjectsLearningAtrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulationCineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel
Midgett D, Thorn S, Ahn S, Uman S, Avendano R, Melvinsdottir I, Lysyy T, Kim J, Duncan J, Humphrey J, Papademetris X, Burdick J, Sinusas A. CineCT platform for in vivo and ex vivo measurement of 3D high resolution Lagrangian strains in the left ventricle following myocardial infarction and intramyocardial delivery of theranostic hydrogel. Journal Of Molecular And Cellular Cardiology 2022, 166: 74-90. PMID: 35227737, PMCID: PMC9035115, DOI: 10.1016/j.yjmcc.2022.02.004.Peer-Reviewed Original ResearchRegional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction
Stacy MR, Lin BA, Thorn SL, Lobb DC, Maxfield MW, Novack C, Zellars KN, Freeburg L, Akar JG, Sinusas AJ, Spinale FG. Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction. Heart Rhythm 2022, 19: 847-855. PMID: 35066183, PMCID: PMC9064890, DOI: 10.1016/j.hrthm.2022.01.022.Peer-Reviewed Original ResearchConceptsAtrial fibrillationMyocardial infarctionRight atrial regionsAtrial regionsPost-MIMMP activityMatrix metalloproteinasesMMP/TIMP profilesNew-onset atrial fibrillationLeft atrial regionsMMP/TIMP expressionLeft atrial appendageMatrix remodelingElectrical stimulation protocolFibrillar collagen contentExtracellular matrix remodelingAF vulnerabilityTIMP profilesAtrial appendagePostmyocardial infarctionMyocardial substrateStimulation protocolNoninvasive molecular imagingTIMP expressionTissue inhibitor
2020
Imaging of Injectable Hydrogels Delivered into Myocardium with SPECT/CT
Uman S, Wang LL, Thorn SL, Liu Z, Duncan JS, Sinusas AJ, Burdick JA. Imaging of Injectable Hydrogels Delivered into Myocardium with SPECT/CT. Advanced Healthcare Materials 2020, 9: e2000294. PMID: 32543053, PMCID: PMC7482444, DOI: 10.1002/adhm.202000294.Peer-Reviewed Original ResearchConceptsInjectable hydrogelsMyocardial infarctionSelf-healing hydrogelsHydrogel mechanical propertiesHybrid single-photon emissionHybrid SPECT/CT imagingMechanical propertiesTomography perfusion imagingAcute porcine modelSPECT/CT imagingSPECT/CTSingle photon emissionInjection forceHyaluronic acid hydrogelsPattern of deliveryTomography/HydrogelsPerfusion defectsPerfusion imagingExcellent radiopacityPorcine modelAcid hydrogelsCT imagingHydrogel deliveryHydrogel injection
2019
Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling
Thorn SL, Barlow SC, Feher A, Stacy MR, Doviak H, Jacobs J, Zellars K, Renaud JM, Klein R, deKemp RA, Khakoo AY, Lee T, Spinale FG, Sinusas AJ. Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic 201Tl Single-Photon Emission Computed Tomography/Computed Tomography Imaging for Evaluation of Early Post-Myocardial Infarction Remodeling. Circulation Cardiovascular Imaging 2019, 12: e009055. PMID: 31707811, PMCID: PMC7250243, DOI: 10.1161/circimaging.119.009055.Peer-Reviewed Original ResearchConceptsMyocardial blood flowSingle photon emissionBlood flowRecombinant TIMP-3Matrix metalloproteinasesR injuryTomography/Intracoronary deliveryMMP activationPost-myocardial infarction remodelingSubsequent left ventricular remodelingHybrid single-photon emissionDual-isotope single-photon emissionTomography/Computed Tomography ImagingLeft ventricular remodelingIschemia/reperfusionPost-MI remodelingPost-myocardial infarctionComputed tomography (CT) imagingIntracoronary infusionVentricular functionSaline groupVentricular remodelingNoninvasive evaluationTreatment groupsDirect List Mode Parametric Reconstruction for Dynamic Cardiac SPECT
Shi L, Lu Y, Wu J, Gallezot JD, Boutagy N, Thorn S, Sinusas AJ, Carson RE, Liu C. Direct List Mode Parametric Reconstruction for Dynamic Cardiac SPECT. IEEE Transactions On Medical Imaging 2019, 39: 119-128. PMID: 31180845, PMCID: PMC7030971, DOI: 10.1109/tmi.2019.2921969.Peer-Reviewed Original ResearchConceptsAppropriate kinetic modelConventional indirect methodImage reconstruction algorithmKinetic modelHigh noise levelsLow count levelsVivo canine studyIndirect methodImage noiseNoise levelParametric reconstructionNoiseReconstruction algorithmFrame imagePatient radiation dose reductionMethodDirect methodLower image noiseAngiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure
Pfau D, Thorn SL, Zhang J, Mikush N, Renaud JM, Klein R, deKemp RA, Wu X, Hu X, Sinusas AJ, Young LH, Tirziu D. Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure. Scientific Reports 2019, 9: 5791. PMID: 30962467, PMCID: PMC6453892, DOI: 10.1038/s41598-019-42113-0.Peer-Reviewed Original ResearchMeSH KeywordsAminobutyratesAngiotensin Receptor AntagonistsAnimalsBiphenyl CompoundsDrug CombinationsHeartHeart FailureMaleMyocardial Reperfusion InjuryMyocardiumNeovascularization, PhysiologicNeprilysinOrganotechnetium CompoundsPeptides, CyclicRatsRats, Inbred LewSingle Photon Emission Computed Tomography Computed TomographyTetrazolesValsartanVascular Endothelial Growth Factor AVentricular RemodelingConceptsSacubitril/valsartanExperimental heart failureHeart failureMyocardial infarctionMyocardial remodelingAngiotensin receptor neprilysin inhibitorAngiotensin receptor blocker valsartanMicroSPECT/CT imagingReceptor blocker valsartanHeart failure patientsProgressive LV dilationGlobal LV functionLV contractile dysfunctionNeprilysin inhibitor sacubitrilBorder zoneLimited remodelingFailure patientsInhibitor therapyMale LewisWeeks treatmentLV dilationLV functionNeprilysin inhibitorContractile dysfunctionInterstitial fibrosisIncisional Negative Pressure Wound Therapy Augments Perfusion and Improves Wound Healing in a Swine Model Pilot Study.
Shah A, Sumpio BJ, Tsay C, Swallow M, Dash B, Thorn SL, Sinusas AJ, Koo A, Hsia HC, Au A. Incisional Negative Pressure Wound Therapy Augments Perfusion and Improves Wound Healing in a Swine Model Pilot Study. Annals Of Plastic Surgery 2019, 82: s222-s227. PMID: 30855392, DOI: 10.1097/sap.0000000000001842.Peer-Reviewed Original ResearchConceptsNegative pressure wound therapyVascular endothelial growth factorClosed woundsUse of NPWTVEGF expressionSurgical wound sitePressure wound therapyMale Yorkshire pigsEnzyme-linked immunosorbent assay resultsEnzyme-linked immunosorbent assayEndothelial growth factorExcisional wound modelImmunosorbent assay resultsControl dressingsPrimary sutureScar evaluationImmunohistochemistry stainingIncision siteNPWT dressingsWound therapyAngiogenesis markersTreatment groupsAppearance of woundsOpen woundsWound healing model
2016
T1-refBlochi: high resolution 3D post-contrast T1 myocardial mapping based on a single 3D late gadolinium enhancement volume, Bloch equations, and a reference T1
Hu C, Sinusas AJ, Huber S, Thorn S, Stacy MR, Mojibian H, Peters DC. T1-refBlochi: high resolution 3D post-contrast T1 myocardial mapping based on a single 3D late gadolinium enhancement volume, Bloch equations, and a reference T1. Journal Of Cardiovascular Magnetic Resonance 2016, 19: 63. PMID: 28821300, PMCID: PMC5563030, DOI: 10.1186/s12968-017-0375-1.Peer-Reviewed Original ResearchAlgorithmsAnimalsCardiomyopathiesComputer SimulationContrast MediaFeasibility StudiesFemaleFibrosisHeart AtriaHumansImage Interpretation, Computer-AssistedImaging, Three-DimensionalMagnetic Resonance ImagingMaleMiddle AgedModels, CardiovascularMonte Carlo MethodOrganometallic CompoundsPhantoms, ImagingPredictive Value of TestsReproducibility of ResultsSus scrofaEffects of an endothelin receptor antagonist, Macitentan, on right ventricular substrate utilization and function in a Sugen 5416/hypoxia rat model of severe pulmonary arterial hypertension
Drozd K, Ahmadi A, Deng Y, Jiang B, Petryk J, Thorn S, Stewart D, Beanlands R, deKemp RA, DaSilva JN, Mielniczuk LM. Effects of an endothelin receptor antagonist, Macitentan, on right ventricular substrate utilization and function in a Sugen 5416/hypoxia rat model of severe pulmonary arterial hypertension. Journal Of Nuclear Cardiology 2016, 24: 1979-1989. PMID: 27688036, DOI: 10.1007/s12350-016-0663-4.Peer-Reviewed Original ResearchConceptsPulmonary arterial hypertensionRV FDG uptakePositron emission tomographyFDG uptakeFTHA uptakeFatty acid metabolismArterial hypertensionRV functionMacitentan treatmentRat modelSevere pulmonary arterial hypertensionWeek 5Effect of macitentanImproved RV functionRV systolic pressureWeeks of hypoxiaEndothelin receptor antagonistsRV ejection fractionHypoxia rat modelSingle subcutaneous injectionMale Sprague-DawleyAcid metabolismMyocardial energy metabolismPAH severitySugen 5416
2015
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy
Albright RA, Stabach P, Cao W, Kavanagh D, Mullen I, Braddock AA, Covo MS, Tehan M, Yang G, Cheng Z, Bouchard K, Yu ZX, Thorn S, Wang X, Folta-Stogniew EJ, Negrete A, Sinusas AJ, Shiloach J, Zubal G, Madri JA, De La Cruz EM, Braddock DT. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy. Nature Communications 2015, 6: 10006. PMID: 26624227, PMCID: PMC4686714, DOI: 10.1038/ncomms10006.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseVascular calcificationArterial calcificationOrphan diseaseCommon diseaseSequelae of diseaseEctopic vascular calcificationInternal elastic laminaPrevent mortalityRenal failureCardiac failureKidney diseaseSubcutaneous administrationRodent modelsAnimal modelsEctopic calcificationVascular wallLarge arteriesElastic laminaDiseaseCalcificationCalciphylaxisDecreased concentrationSclerosisArteryDeletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*
Cattin ME, Wang J, Weldrick JJ, Roeske CL, Mak E, Thorn SL, DaSilva JN, Wang Y, Lusis AJ, Burgon PG. Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation*. Journal Of Biological Chemistry 2015, 290: 26699-26714. PMID: 26359501, PMCID: PMC4646324, DOI: 10.1074/jbc.m115.678433.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsCardiomegalyCarrier ProteinsCo-Repressor ProteinsFemaleGene Expression RegulationGenome-Wide Association StudyHeart Function TestsHemodynamicsIsoproterenolMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumMyocytes, CardiacNuclear ProteinsPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionStress, PhysiologicalTOR Serine-Threonine KinasesUltrasonographyConceptsAKT/mTOR pathwayGenome-wide association studiesAkt/mammalian targetMTOR pathwayAkt/mTOR activityAkt/mTORUnique proteinsUnknown functionAssociation studiesMTOR activityMammalian targetCardiac adaptationRegenerative abilityGenetic associationAdult heartPathwayHomeostasisMyocardial metabolic abnormalitiesNormal cardiac functionAdaptationEarly responseMetabolic abnormalitiesCardiac functionMLIPCardiac stressCardiac β-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses
Haley JM, Thackeray JT, Thorn SL, DaSilva JN. Cardiac β-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses. PLOS ONE 2015, 10: e0127581. PMID: 25996498, PMCID: PMC4440709, DOI: 10.1371/journal.pone.0127581.Peer-Reviewed Original ResearchConceptsZucker diabetic fattyΒ-AR expressionWeeks of ageΒ2-AR expressionΒ-adrenoceptor expressionZDF ratsΒ3-ARFree fatty acidsType 2 diabetic Zucker diabetic fattyType 2 diabetic ZDF ratsDiabetic Zucker diabetic fattyZucker diabetic fatty ratsType 2 diabetes progressesType 2 diabetes modelWestern blottingCardiac β-ARΒ1-AR expressionDiabetic fatty ratsDiabetic ZDF ratsType 2 diabetesModel of hyperglycemiaΒ-AR subtypesBrown adipose tissueDiastolic functionSystolic functionInsulin therapy normalizes reduced myocardial β-adrenoceptors at both the onset and after sustained hyperglycemia in diabetic rats
Haley JM, Thackeray JT, Kolajova M, Thorn SL, DaSilva JN. Insulin therapy normalizes reduced myocardial β-adrenoceptors at both the onset and after sustained hyperglycemia in diabetic rats. Life Sciences 2015, 132: 101-107. PMID: 25934520, DOI: 10.1016/j.lfs.2015.03.024.Peer-Reviewed Original ResearchConceptsCardiac β-ARPositron emission tomographyΒ-ARHeart rateInsulin therapyDiabetes mellitusΒ-adrenoceptorsCV functionWestern blottingInsulin effectDuration of hyperglycemiaMyocardial β-adrenoceptorsΒ-AR expressionOnset of hyperglycemiaWeeks of hyperglycemiaCardiac β-adrenoceptorsΒ-AR subtypesReduced heart rateMyocardial β-ARsGlycemic therapyStreptozotocin ratsSerial echocardiographySTZ ratsGlycemic controlCardiovascular dysfunctionCreation of clinically relevant model of chronic heart failure: Application of multi-modality imaging to define physiology
Thorn S, Sinusas AJ. Creation of clinically relevant model of chronic heart failure: Application of multi-modality imaging to define physiology. Journal Of Nuclear Cardiology 2015, 22: 673-676. PMID: 25698482, DOI: 10.1007/s12350-015-0081-z.Peer-Reviewed Original Research