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
Matrix 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 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 groupsAngiotensin 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 fibrosis
2016
Quantitative Analysis of Dynamic 123I-mIBG SPECT Imaging Data in Healthy Humans with a Population-Based Metabolite Correction Method
Wu J, Lin SF, Gallezot JD, Chan C, Prasad R, Thorn S, Stacy MR, Huang Y, Zonouz TH, Liu YH, Lampert RJ, Carson RE, Sinusas AJ, Liu C. Quantitative Analysis of Dynamic 123I-mIBG SPECT Imaging Data in Healthy Humans with a Population-Based Metabolite Correction Method. Journal Of Nuclear Medicine 2016, 57: 1226-1232. PMID: 27081169, DOI: 10.2967/jnumed.115.171710.Peer-Reviewed Original Research3-IodobenzylguanidineAdultAgedAlgorithmsArtifactsComputer SimulationFemaleHeartHumansImage EnhancementImage Interpretation, Computer-AssistedMaleMiddle AgedModels, CardiovascularModels, StatisticalMyocardiumRadiopharmaceuticalsReproducibility of ResultsSensitivity and SpecificityTissue DistributionTomography, Emission-Computed, Single-Photon
2015
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*
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 dysfunction
2014
Glutaredoxin-2 Is Required to Control Oxidative Phosphorylation in Cardiac Muscle by Mediating Deglutathionylation Reactions*
Mailloux RJ, Xuan JY, McBride S, Maharsy W, Thorn S, Holterman CE, Kennedy CR, Rippstein P, deKemp R, da Silva J, Nemer M, Lou M, Harper ME. Glutaredoxin-2 Is Required to Control Oxidative Phosphorylation in Cardiac Muscle by Mediating Deglutathionylation Reactions*. Journal Of Biological Chemistry 2014, 289: 14812-14828. PMID: 24727547, PMCID: PMC4031535, DOI: 10.1074/jbc.m114.550574.Peer-Reviewed Original ResearchReply: Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG
Thorn SL, deKemp R, Dumouchel T, Klein R, Renaud JN, Wells RG, Gollob M, Beanlands RS, DaSilva JN. Reply: Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG. Journal Of Nuclear Medicine 2014, 55: 866-867. PMID: 24652829, DOI: 10.2967/jnumed.114.138214.Peer-Reviewed Original ResearchThe role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium
Ahmadi A, McNeill B, Vulesevic B, Kordos M, Mesana L, Thorn S, Renaud JM, Manthorp E, Kuraitis D, Toeg H, Mesana TG, Davis DR, Beanlands RS, DaSilva JN, deKemp RA, Ruel M, Suuronen EJ. The role of integrin α2 in cell and matrix therapy that improves perfusion, viability and function of infarcted myocardium. Biomaterials 2014, 35: 4749-4758. PMID: 24631247, DOI: 10.1016/j.biomaterials.2014.02.028.Peer-Reviewed Original ResearchConceptsMatrix therapyMouse myocardial infarction modelMyocardial infarction modelCardiac cell therapySynergistic therapeutic effectTherapeutic effectMyocardial perfusionParacrine propertiesInfarcted myocardiumAngiogenic cellsInfarction modelOverall efficacyTherapyCell therapyAngiogenic potentialCACSΑ5 integrinIntegrin α2EngraftmentIntegrin α5PerfusionCellsIntegrinsCollagen matrixCAC function
2013
Repeatable Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG: Evaluation of Tracer Kinetics in a Type 1 Diabetes Model
Thorn SL, deKemp RA, Dumouchel T, Klein R, Renaud JM, Wells RG, Gollob MH, Beanlands RS, DaSilva JN. Repeatable Noninvasive Measurement of Mouse Myocardial Glucose Uptake with 18F-FDG: Evaluation of Tracer Kinetics in a Type 1 Diabetes Model. Journal Of Nuclear Medicine 2013, 54: 1637-1644. PMID: 23940301, DOI: 10.2967/jnumed.112.110114.Peer-Reviewed Original ResearchConceptsMyocardial glucose uptakeImage-derived blood input functionAcute insulin treatmentInsulin treatmentBlood activityType 1 diabetic miceType 1 diabetic mouse modelML/min/Glucose uptakeVena cava diameterMyocardial glucose uptake ratesDiabetic mouse modelType 1 diabetesStandardized uptake valueTest-retest repeatabilityAcute insulin stimulationDiabetic miceCoefficient of repeatabilityFDG-PETBland-Altman analysisMyocardial glucoseContrast CTBaseline scanMouse modelTime-activity curves
2011
Reduced CGP12177 binding to cardiac β-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats
Thackeray JT, Parsa-Nezhad M, Kenk M, Thorn SL, Kolajova M, Beanlands RS, DaSilva JN. Reduced CGP12177 binding to cardiac β-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats. Nuclear Medicine And Biology 2011, 38: 1059-1066. PMID: 21831645, DOI: 10.1016/j.nucmedbio.2011.04.002.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAnimalsBiomarkersBlotting, WesternDiabetes Mellitus, ExperimentalDiet, High-FatGene Expression RegulationHyperglycemiaMaleMyocardiumPositron-Emission TomographyPropanolaminesProtein BindingRatsRats, Sprague-DawleyReceptors, Adrenergic, beta-1Receptors, Adrenergic, beta-2Substrate SpecificityConceptsAbnormal sympathetic nervous systemΒ-AR expressionSympathetic nervous systemDiabetic rat heartsSingle intraperitoneal injectionVehicle-treated controlsInfusion of isoproterenolCardiac β-adrenoceptorsΒ-AR subtypesΒ-AR antagonistsSpecific bindingHalf of ratsNormal Sprague-DawleyΒ-AR stimulationPositron emission tomographyΒ-adrenoceptor signalingCardiac bindingAR expressionCardiac dysfunctionDiabetic ratsInsulin resistanceSustained hyperglycemiaIntraperitoneal injectionΒ-adrenoceptorsDiet feedingAnalysis of (R)- and (S)-[11C]rolipram Kinetics in Canine Myocardium for the Evaluation of Phosphodiesterase-4 with PET
Lortie M, DaSilva JN, Kenk M, Thorn S, Davis D, Birnie D, Beanlands RS, deKemp RA. Analysis of (R)- and (S)-[11C]rolipram Kinetics in Canine Myocardium for the Evaluation of Phosphodiesterase-4 with PET. Molecular Imaging And Biology 2011, 14: 225-236. PMID: 21424298, DOI: 10.1007/s11307-011-0482-6.Peer-Reviewed Original Research
2010
Kinetic model‐based factor analysis of dynamic sequences for 82‐rubidium cardiac positron emission tomography
Klein R, Beanlands RS, Wassenaar RW, Thorn SL, Lamoureux M, DaSilva JN, Adler A, deKemp RA. Kinetic model‐based factor analysis of dynamic sequences for 82‐rubidium cardiac positron emission tomography. Medical Physics 2010, 37: 3995-4010. PMID: 20879561, DOI: 10.1118/1.3438474.Peer-Reviewed Original ResearchAlterations of pre- and postsynaptic noradrenergic signaling in a rat model of adriamycin-induced cardiotoxicity
Kenk M, Thackeray JT, Thorn SL, Dhami K, Chow BJ, Ascah KJ, DaSilva JN, Beanlands RS. Alterations of pre- and postsynaptic noradrenergic signaling in a rat model of adriamycin-induced cardiotoxicity. Journal Of Nuclear Cardiology 2010, 17: 254-263. PMID: 20182926, DOI: 10.1007/s12350-009-9190-x.Peer-Reviewed Original ResearchConceptsPositron emission tomographyRat modelNoradrenergic signalingHeart/body weight ratioBeta-adrenergic receptor antagonistMyocardial noradrenaline levelsSympathetic nervous systemBody weight ratioPhosphodiesterase 4 inhibitorBeta-adrenergic receptorsVentricle free wallAnthracycline chemotherapeutic agentDesipramine treatmentNoradrenaline levelsNoradrenaline uptakeAnthracycline cardiotoxicityReceptor antagonistAcute increaseCardiac functionRight ventricleLeft atriumInteraction of preAdriamycin cardiotoxicityFree wallNervous system
2009
In Vivo Assessment of Myocardial Glucose Uptake by Positron Emission Tomography in Adults With the PRKAG2 Cardiac Syndrome
Ha AC, Renaud JM, deKemp RA, Thorn S, DaSilva J, Garrard L, Yoshinaga K, Abraham A, Green MS, Beanlands RS, Gollob MH. In Vivo Assessment of Myocardial Glucose Uptake by Positron Emission Tomography in Adults With the PRKAG2 Cardiac Syndrome. Circulation Cardiovascular Imaging 2009, 2: 485-491. PMID: 19920047, DOI: 10.1161/circimaging.109.853291.Peer-Reviewed Original ResearchMeSH KeywordsAdultAMP-Activated Protein KinasesCase-Control StudiesEchocardiographyFemaleFluorodeoxyglucose F18Heart DiseasesHumansMaleMetabolic DiseasesMiddle AgedMutationMyocardiumPhenotypeRadiographic Image Interpretation, Computer-AssistedRubidium RadioisotopesStatistics, NonparametricSyndromeTomography, Emission-ComputedConceptsMyocardial glucose uptakeSignificant myocardial scarFDG-PET imagingPRKAG2 cardiac syndromeCardiac syndromeGlucose uptakeAdult patientsMyocardial scarMetabolic diseasesControl groupMedian blood glucoseEuglycemic hyperinsulinemic clampStable blood glucose levelsBlood glucose levelsInherited metabolic diseaseMin/Positron emission tomography (PET) imagingEmission Tomography ImagingPositron emission tomographyMyocardial glucose transportPerfusion scanBlood glucoseControl subjectsHyperinsulinemic clampAffected patients
2006
In vivo selective binding of (R)-[11C]rolipram to phosphodiesterase-4 provides the basis for studying intracellular cAMP signaling in the myocardium and other peripheral tissues
Kenk M, Greene M, Thackeray J, deKemp RA, Lortie M, Thorn S, Beanlands RS, DaSilva JN. In vivo selective binding of (R)-[11C]rolipram to phosphodiesterase-4 provides the basis for studying intracellular cAMP signaling in the myocardium and other peripheral tissues. Nuclear Medicine And Biology 2006, 34: 71-77. PMID: 17210463, DOI: 10.1016/j.nucmedbio.2006.10.002.Peer-Reviewed Original ResearchMeSH Keywords3',5'-Cyclic-AMP PhosphodiesterasesAnimalsBrainCarbon RadioisotopesCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 1Cyclic Nucleotide Phosphodiesterases, Type 4HeartMaleMetabolic Clearance RateMyocardiumOrgan SpecificityPhosphodiesterase InhibitorsProtein BindingRadionuclide ImagingRadiopharmaceuticalsRatsRats, Sprague-DawleyRolipramSensitivity and SpecificityTissue DistributionConceptsPhosphodiesterase 4BAY 60Ro 20Male Sprague-Dawley ratsIntracellular cAMPSprague-Dawley ratsNeurohormonal modulationPeripheral tissuesAutoradiography studiesAdipose tissuePDE4 levelsTracer uptakeVivo findingsCAMP-mediated signalingBiodistribution studiesPDE4 activityRolipramSkeletal muscleCAMP levelsTracer retentionCardiac regionCilostazolMyocardiumZaprinastTissue