2019
Angiotensin 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
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
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
Cardiac 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 dysfunctionPET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction
Ahmadi A, Thorn SL, Alarcon EI, Kordos M, Padavan DT, Hadizad T, Cron GO, Beanlands RS, DaSilva JN, Ruel M, deKemp RA, Suuronen EJ. PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction. Biomaterials 2015, 49: 18-26. PMID: 25725551, DOI: 10.1016/j.biomaterials.2015.01.016.Peer-Reviewed Original ResearchConceptsMyocardial infarctionPositron emission tomographyPET imagingMouse modelNon-invasive PET imagingCardiac regeneration therapyIschemic territoryPET resultsInfarcted myocardiumEmission tomographyCollagen matrixMyocardial injectionEarly retentionPromising modalityRegeneration therapyInfarctionLabeling efficiencyMyocardiumFluorescence imagingImagingBiodistributionInjectionQdot labelingEx
2012
18F-FDG Cell Labeling May Underestimate Transplanted Cell Homing: More Accurate, Efficient, and Stable Cell Labeling with Hexadecyl-4-[18F]Fluorobenzoate for in Vivo Tracking of Transplanted Human Progenitor Cells by Positron Emission Tomography
Zhang Y, Dasilva JN, Hadizad T, Thorn S, Kuraitis D, Renaud JM, Ahmadi A, Kordos M, Dekemp RA, Beanlands RS, Suuronen EJ, Ruel M. 18F-FDG Cell Labeling May Underestimate Transplanted Cell Homing: More Accurate, Efficient, and Stable Cell Labeling with Hexadecyl-4-[18F]Fluorobenzoate for in Vivo Tracking of Transplanted Human Progenitor Cells by Positron Emission Tomography. Cell Transplantation 2012, 21: 1821-1835. PMID: 22469629, DOI: 10.3727/096368911x637416.Peer-Reviewed Original ResearchConceptsCirculating Progenitor CellsPositron emission tomographyEmission tomographyCell therapyPET imagingCell transplantation groupProgenitor cellsCoronary artery ligationRat myocardial infarction modelInfarct border zoneHeart tissue sectionsMyocardial infarction modelBorder zoneCardiac cell therapyTransplantation groupIschemic/Artery ligationH posttransplantationBest modalityHuman progenitor cellsIntramyocardial injectionH postinjectionInjection siteTissue biodistributionInfarction modelUniformity and repeatability of normal resting myocardial blood flow in rats using [13N]-ammonia and small animal PET
Lamoureux M, Thorn S, Dumouchel T, Renaud JM, Klein R, Mason S, Lortie M, DaSilva JN, Beanlands RS, deKemp RA. Uniformity and repeatability of normal resting myocardial blood flow in rats using [13N]-ammonia and small animal PET. Nuclear Medicine Communications 2012, 33: 917-925. PMID: 22692581, DOI: 10.1097/mnm.0b013e328355d8bc.Peer-Reviewed Original Research
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 feeding
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
Distinct Early Signaling Events Resulting From the Expression of the PRKAG2 R302Q Mutant of AMPK Contribute to Increased Myocardial Glycogen
Folmes KD, Chan AY, Koonen DP, Pulinilkunnil TC, Baczkó I, Hunter BE, Thorn S, Allard MF, Roberts R, Gollob MH, Light PE, Dyck JR. Distinct Early Signaling Events Resulting From the Expression of the PRKAG2 R302Q Mutant of AMPK Contribute to Increased Myocardial Glycogen. Circulation Genomic And Precision Medicine 2009, 2: 457-466. PMID: 20031621, DOI: 10.1161/circgenetics.108.834564.Peer-Reviewed Original ResearchConceptsTransgenic miceR302Q mutationGlycogen contentAcute expressionCardiomyocyte-restricted expressionAMPK activationTransgenic adult miceNeonatal rat cardiomyocytesChronic modelWolff-ParkinsonGlycogen synthase activityWhite syndromeCardiac hypertrophyAdult miceGlycogen storage cardiomyopathyMyocardial glycogenDirect effectCompensatory alterationsRat cardiomyocytesFamilial formsMiceEarly signaling eventCardiomyopathyAMPK activityHeartReduced in vivo phosphodiesterase-4 response to acute noradrenaline challenge in diet-induced obese rats
Greene M, Thackeray JT, Kenk M, Thorn SL, Bevilacqua L, Harper ME, Beanlands RS, DaSilva JN. Reduced in vivo phosphodiesterase-4 response to acute noradrenaline challenge in diet-induced obese rats. Canadian Journal Of Physiology And Pharmacology 2009, 87: 196-202. PMID: 19295660, DOI: 10.1139/y09-001.Peer-Reviewed Original ResearchConceptsDiet-induced obeseDR ratsDiet-induced obese ratsObese animal modelsSympathetic nervous activityPersistence of obesityHigh-fat dietPhosphodiesterase 4 inhibitorWeeks of feedingEnergy expenditure measuresDIO animalsNoradrenaline challengeDesipramine pretreatmentObese ratsCaloric intakeNoradrenaline stimulationNervous activityAnimal modelsPDE4 levelsNormal increaseWeight gainH pretreatmentSkeletal muscleRatsProgressive alteration
2008
Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells
Zhang Y, Thorn S, DaSilva JN, Lamoureux M, deKemp RA, Beanlands RS, Ruel M, Suuronen EJ. Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells. Circulation Cardiovascular Imaging 2008, 1: 197-204. PMID: 19808543, DOI: 10.1161/circimaging.108.781120.Peer-Reviewed Original ResearchConceptsPositron emission tomographyIschemic hind limbIschemic hind limb musclesCirculating Progenitor CellsHind limbProgenitor cellsRats 2 weeksFemoral artery ligationNonspecific tissueHind limb musclesMechanism of actionEarly posttransplantationCollagen matrixSmall animal positron emission tomographyArtery ligationMinutes postinjectionProgenitor cell retentionAnimal positron emission tomographyLimb musclesCell therapyHuman CPCsTarget tissuesPosttransplantationTomographyFDG
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