2023
Continuous positive airway pressure (CPAP) increases CSF flow and glymphatic transport
Ozturk B, Koundal S, Al Bizri E, Chen X, Gursky Z, Dai F, Lim A, Heerdt P, Kipnis J, Tannenbaum A, Lee H, Benveniste H. Continuous positive airway pressure (CPAP) increases CSF flow and glymphatic transport. JCI Insight 2023, 8: e170270. PMID: 37159262, PMCID: PMC10371231, DOI: 10.1172/jci.insight.170270.Peer-Reviewed Original ResearchConceptsContinuous positive airway pressurePositive airway pressureGlymphatic transportAirway pressureIntracranial pressureEnd-expiratory lung volumeCSF bulk flowCerebrospinal fluid flowArterial oxygenationUpper airwayLung volumeCPAP deviceRespiratory functionClearance functionTherapeutic benefitSkull baseAnesthetized rodentsCSF flowFluid homeostasisPhysiological testingLymphatic systemFunctional crosstalkClinical devicesAirwayRatsIntegrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application
Heerdt P, Martin-Flores M, Oakland H, Joseph P, Singh I. Integrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application. Journal Of Cardiothoracic And Vascular Anesthesia 2023, 37: 1929-1937. PMID: 37422337, PMCID: PMC10529383, DOI: 10.1053/j.jvca.2023.06.011.Peer-Reviewed Original ResearchConceptsRight heart catheterizationHeart catheterizationDiastolic functionRV volumesBeat measuresDiagnostic right heart catheterizationReference standardRight ventricular contractilityEnd-diastolic pressurePressure waveform analysisEnd-systolic elastancePotential clinical utilityClinical applicationRV volume measurementsVolume measurementsRV contractilityRV systolicVentricular contractilityRV pressureBland-Altman analysisClinical utilityAnesthetized swineNitric oxideExperimental modelContractilityCharacterizing the Spatiotemporal Transcriptomic Response of the Right Ventricle to Acute Pressure Overload
Kheyfets V, Kumar S, Heerdt P, Ichimura K, Brown R, Lucero M, Essafri I, Williams S, Stenmark K, Spiekerkoetter E. Characterizing the Spatiotemporal Transcriptomic Response of the Right Ventricle to Acute Pressure Overload. International Journal Of Molecular Sciences 2023, 24: 9746. PMID: 37298696, PMCID: PMC10253685, DOI: 10.3390/ijms24119746.Peer-Reviewed Original ResearchConceptsPressure overloadChronic RV pressure overloadExperimental pulmonary hypertension modelsRV pressure overloadTime pointsPulmonary hypertension modelRV outflow tractTranscriptomic signaturesAcute pressure overloadRight ventricular tissueDifferent time pointsPulmonary embolismHypertension modelSevere PEAcute increaseInitial insultOutflow tractRight ventricleRV apexVentricular tissueControl tissuesRatsSeverityWeeksTissue
2020
The glymphatic system and its role in cerebral homeostasis
Benveniste H, Elkin R, Heerdt P, Koundal S, Xue Y, Lee H, Wardlaw J, Tannenbaum A. The glymphatic system and its role in cerebral homeostasis. Journal Of Applied Physiology 2020, 129: 1330-1340. PMID: 33002383, PMCID: PMC7792843, DOI: 10.1152/japplphysiol.00852.2019.Peer-Reviewed Original Research
2019
Glymphatic System Function in Relation to Anesthesia and Sleep States
Benveniste H, Heerdt PM, Fontes M, Rothman DL, Volkow ND. Glymphatic System Function in Relation to Anesthesia and Sleep States. Anesthesia & Analgesia 2019, 128: 747-758. PMID: 30883420, DOI: 10.1213/ane.0000000000004069.Peer-Reviewed Original ResearchConceptsEye movement sleepGlymphatic systemMovement sleepNon-rapid eye movement sleepRapid eye movement (REM) sleepTight blood-brain barrierCentral nervous system tissueCerebral oxygen consumptionCritical care settingBlood-brain barrierGlymphatic system functionCentral nervous systemNervous system tissueCerebrospinal fluid flowAnesthetic regimensBrain glymphatic systemBrain parenchymaCognitive dysfunctionCare settingsNervous systemClinical explorationWaste clearanceWakefulness persistLymphatic systemKey anatomical components
2018
Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine.
Savarese JJ, Sunaga H, McGilvra JD, Belmont MR, Murrell MT, Jeannotte E, Cooke FE, Wastila WB, Heerdt PM. Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine. Anesthesiology 2018, 129: 970-988. PMID: 30212413, DOI: 10.1097/aln.0000000000002408.Peer-Reviewed Original ResearchConceptsNeuromuscular blocking agentsMean arterial pressureBlocking agentArterial pressureNeuromuscular blockadeHeart rateNew neuromuscular blocking agentRhesus monkeysNondepolarizing neuromuscular blocking agentDuration of actionStudy of bolusCirculatory effectsPreclinical pharmacologyControl infusionInstitutional Animal CareED95Large dosesSpontaneous recoveryGantacuriumDose ratioL-cysteineInfusionBolusUse CommitteeRecovery interval
2017
Accuracy of a Simulation Algorithm for Modelling LV Contractility, Diastolic Capacitance, and Energetics Using Data Available From Common Hemodynamic Monitors and Echocardiography
Heerdt PM, Korfhagen S, Ezz H, Oromendia C. Accuracy of a Simulation Algorithm for Modelling LV Contractility, Diastolic Capacitance, and Energetics Using Data Available From Common Hemodynamic Monitors and Echocardiography. Journal Of Cardiothoracic And Vascular Anesthesia 2017, 32: 381-388. PMID: 29153929, DOI: 10.1053/j.jvca.2017.09.032.Peer-Reviewed Original ResearchAnnexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases
Luo M, Flood EC, Almeida D, Yan L, Berlin DA, Heerdt PM, Hajjar KA. Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases. Journal Of Experimental Medicine 2017, 214: 2535-2545. PMID: 28694388, PMCID: PMC5584111, DOI: 10.1084/jem.20160652.Peer-Reviewed Original ResearchConceptsAlveolar hypoxiaVascular endothelial cadherinMicrovascular integrityPulmonary edemaSrc homology phosphatase 2Vascular integrityEndothelial cellsVascular endothelial growth factorMicrovascular endothelial cellsEndothelial growth factorAdherens junction protein vascular endothelial cadherinEndothelial cadherinAirway obstructionNeutrophil infiltrationPulmonary microvasculatureAnnexin A2 functionsVascular leakLung parenchymaMice displayAltitude sicknessBarrier functionGrowth factorHypoxiaPhospholipid-binding proteinsProtein tyrosine phosphataseSingle-lung ventilation and oxidative stress
Heerdt PM, Stowe DF. Single-lung ventilation and oxidative stress. Current Opinion In Anaesthesiology 2017, 30: 42-49. PMID: 27783023, DOI: 10.1097/aco.0000000000000410.Peer-Reviewed Original ResearchConceptsSingle-lung ventilationOxidative stressRe-expanded lungHypoxic pulmonary vasoconstrictionRedistribution of bloodLocal tissue hypoxiaPostoperative disruptionPulmonary vasoconstrictionReperfusion responseAtelectatic lungTissue hypoxiaClinical dataReactive oxygenSystemic effectsOrgan functionLungNitrosative stressVentilationNitrogen speciesVasoconstrictionAgreement of Bioreactance Cardiac Output Monitoring With Thermodilution During Hemorrhagic Shock and Resuscitation in Adult Swine
Berlin DA, Peprah-Mensah H, Manoach S, Heerdt PM. Agreement of Bioreactance Cardiac Output Monitoring With Thermodilution During Hemorrhagic Shock and Resuscitation in Adult Swine. Critical Care Medicine 2017, 45: e195-e201. PMID: 27749345, DOI: 10.1097/ccm.0000000000002071.Peer-Reviewed Original ResearchConceptsNoninvasive cardiac output monitoringCardiac output monitoringThermodilution cardiac outputCardiac outputOutput monitoringArtery catheterHemorrhagic shockBolus thermodilutionIntermittent bolus thermodilutionFemoral artery catheterPulmonary artery catheterAdult porcine modelBlood pressure measurementsLaboratory animal investigationFour-quadrant plotLimits of agreementShed bloodBland-Altman analysisAnimal investigationsPlasma lactateThermodilution measurementsResuscitationYorkshire swineAdult swinePorcine model
2015
Effect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats.
Martin-Flores M, Cheetham J, Campoy L, Sakai DM, Heerdt PM, Gleed RD. Effect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats. American Journal Of Veterinary Research 2015, 76: 216-23. PMID: 25710757, DOI: 10.2460/ajvr.76.3.216.Peer-Reviewed Original ResearchConceptsDuration of apneaHemoglobin oxygen saturationLast doseLaryngeal stimulationNeuromuscular blockOxygen saturationPelvic limbsLaryngeal mask airwayComplete neuromuscular blockDomestic shorthair catAdult domestic shorthair catsHealthy adult domestic shorthair catsMask airwayLaryngeal maskSE durationAnesthetized catsHemoglobin desaturationLaryngospasmShorthair catClinical relevanceGantacuriumHealthy catsApneaRima glottidisDose
2014
Regulation of Protein Phosphatase 1I by Cdc25C-associated Kinase 1 (C-TAK1) and PFTAIRE Protein Kinase*
Platholi J, Federman A, Detert JA, Heerdt P, Hemmings HC. Regulation of Protein Phosphatase 1I by Cdc25C-associated Kinase 1 (C-TAK1) and PFTAIRE Protein Kinase*. Journal Of Biological Chemistry 2014, 289: 23893-23900. PMID: 25028520, PMCID: PMC4156073, DOI: 10.1074/jbc.m114.557744.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1IC-TAK1Protein kinaseKinase 1GSK-3Protein phosphatase 1Phosphatase activityPP-1cThr-72Multisite phosphorylationActivating residuesPhosphatase 1Regulatory subunitSer-86Ser-71Subsequent phosphorylationMajor endogenous formsInhibitor 2PhosphorylationKinaseCdc25CEndogenous formPFTK1ResiduesActivationComparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.
Diaz LL, Zhang J, Heerdt PM. Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits. Journal Of The American Association For Laboratory Animal Science 2014, 53: 283-9. PMID: 24827571, PMCID: PMC4128567.Peer-Reviewed Original ResearchConceptsNeuromuscular blocking drugsRecovery indexNew Zealand white rabbitsPotential side effectsCross-over designZealand white rabbitsComparative PharmacodynamicsBlocking drugsPharmacologic reversalMuscle twitchCisatracuriumPancuroniumAnesthetized rabbitsSide effectsCW002Cholinergic manipulationsSurvival proceduresSimilar onsetWhite rabbitsEffective doseSurvival studiesLonger durationDrugsRabbitsTime course
2013
NHE Isoform Switching and KChIP2 Upregulation in Aging Porcine Atria
Kant R, Hu Z, Malhotra JK, Krogh-Madsen T, Christini DJ, Heerdt PM, Abbott GW. NHE Isoform Switching and KChIP2 Upregulation in Aging Porcine Atria. PLOS ONE 2013, 8: e82951. PMID: 24376615, PMCID: PMC3871617, DOI: 10.1371/journal.pone.0082951.Peer-Reviewed Original ResearchConceptsAtrial fibrillationMyocyte action potential durationHuman cardiac physiologyCessation of stimulationAction potential durationLarge animal modelSodium-hydrogen exchangerReperfusion arrhythmiasNHE1-specific inhibitorMyocardial responsivenessPharmacological responsivenessPharmacologic efficacyYoung adult pigsAtrial tissuePotential durationTherapeutic targetAnimal modelsCardiac pathologyKChIP2 expressionReal-time qPCRPotential molecular basisTherapeutic agentsCardiac physiologyFemale swineYoung adults
2012
Transcriptomic analysis reveals atrial KCNE1 down‐regulation following lung lobectomy
Heerdt PM, Kant R, Hu Z, Kanda VA, Christini DJ, Malhotra JK, Abbott GW. Transcriptomic analysis reveals atrial KCNE1 down‐regulation following lung lobectomy. Journal Of Molecular And Cellular Cardiology 2012, 53: 350-353. PMID: 22641150, PMCID: PMC3418454, DOI: 10.1016/j.yjmcc.2012.05.010.Peer-Reviewed Original ResearchConceptsEffective refractory periodLone atrial fibrillationAtrial fibrillationPostoperative AFLung lobectomyLeft atriumNew-onset postoperative atrial fibrillationMean pulmonary artery pressurePostoperative atrial fibrillationPulmonary vascular resistanceUpper lung lobectomyPulmonary artery pressureTelemetric ECGArtery pressureVascular resistanceMajor surgeryHemodynamic variablesFunction polymorphismLA tissuesRefractory periodWestern blottingProtein levelsGene sequence variantsMolecular changesLobectomy
2011
Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles
Heerdt PM, Wagner CL, DeMais M, Savarese JJ. Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles. Journal Of Pharmacological And Toxicological Methods 2011, 64: 111-118. PMID: 21440649, DOI: 10.1016/j.vascn.2011.03.006.Peer-Reviewed Original ResearchConceptsCardiac outputAortic blood flowDrug-induced changesBlood flowAcute drug-induced changesNoninvasive cardiac output monitoringNon-invasive measurementOpen-chest beaglesNeuromuscular blocking drugsPreclinical drug evaluationCardiac output monitoringDrug evaluation studiesML/minSimultaneous CO measurementsBlocking drugsAcute alterationsAortic rootPreclinical screeningChest instrumentationNICOMCO measurementsOutput monitoringDrug evaluationInvasive measurementsInvasive instrumentation
2010
Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011
Savarese JJ, McGilvra JD, Sunaga H, Belmont MR, Van Ornum SG, Savard PM, Heerdt PM. Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011. Anesthesiology 2010, 113: 58-73. PMID: 20526187, DOI: 10.1097/aln.0b013e3181dc1b5b.Peer-Reviewed Original ResearchMeSH KeywordsAlkenesAnimalsAtracuriumChemical PhenomenaCholinesterase InhibitorsChromatography, High Pressure LiquidCysteineDose-Response Relationship, DrugDrug InteractionsEdrophoniumHaplorhiniIsoquinolinesMacaca mulattaMaleMaleatesNeostigmineNeuromuscular BlockadeNeuromuscular Blocking AgentsStructure-Activity RelationshipConceptsDuration of blockED95 dosesNeuromuscular blockadeNeuromuscular blockersNovel agentsTwitch inhibitionCysteine adductionGantacuriumExogenous L-cysteineIntermediate durationAdductionL-cysteineED95Preliminary dataBlockadeAntagonismChemical antagonismHigh-performance liquid chromatographyDurationMinRapid adductionAdduction productsCisatracuriumLiquid chromatographyBlockersCysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs
Sunaga H, Malhotra JK, Yoon E, Savarese JJ, Heerdt PM. Cysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs. Anesthesiology 2010, 112: 900-909. PMID: 20234310, DOI: 10.1097/aln.0b013e3181d31f8c.Peer-Reviewed Original ResearchConceptsOrgan toxicityHeart rateIsoflurane-nitrous oxide anesthesiaAcute cardiovascular effectsNeuromuscular blocking drugsDose-response relationshipDose-dependent mannerEndogenous L-cysteineCardiovascular effectsHemodynamic effectsMedian durationArterial pressureBlood pressureBlocking drugsHistologic evidenceNeuromuscular blockadeOxide anesthesiaTwitch recoveryMuscle recoveryHistopathologic analysisMuscle twitchLarge doseCW002Additional groupDosePharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs
Heerdt PM, Malhotra JK, Pan BY, Sunaga H, Savarese JJ. Pharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs. Anesthesiology 2010, 112: 910-916. PMID: 20234311, DOI: 10.1097/aln.0b013e3181d31f71.Peer-Reviewed Original ResearchConceptsX ED95Neuromuscular blocking drugsCardiopulmonary side effectsVascular resistanceArterial pressureBlocking drugsCardiac outputHistamine releaseSide effectsMean pulmonary artery pressurePulmonary artery pressurePulmonary vascular resistanceSystemic vascular resistanceMean arterial pressurePulmonary arterial pressureArtery pressureHemodynamic effectsPulmonary complianceVentricular contractilityInspiratory pressureNeuromuscular blockadeVentricular pressureED95Large dosesCW002
2008
The Emerging Role of Minimally Invasive Surgical Techniques for the Treatment of Lung Malignancy in the Elderly
Heerdt PM, Park BJ. The Emerging Role of Minimally Invasive Surgical Techniques for the Treatment of Lung Malignancy in the Elderly. Anesthesiology Clinics 2008, 26: 315-324. PMID: 18456216, DOI: 10.1016/j.anclin.2008.01.009.Peer-Reviewed Original ResearchConceptsPerioperative morbidityEarly-stage lung cancerVideo-assisted thoracoscopic lobectomyLung cancer surgeryInvasive operative techniquesInvasive surgical techniquesElderly patientsPulmonary resectionSurgical therapyLung malignancyPreoperative interventionSurgical treatmentCancer surgeryConventional thoracotomyOncologic efficacyThoracoscopic lobectomyGeriatric populationLung cancerAdvanced ageSurgical techniqueOperative techniqueClear associationEmerging RoleGeneral agingMorbidity