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 intervalPharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers
Kaullen JD, Owen JS, Brouwer KLR, Heerdt PM, Lien CA, Savarese JJ, Schmith VD. Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers. Anesthesiology 2018, 128: 1107-1116. PMID: 29494403, PMCID: PMC5953789, DOI: 10.1097/aln.0000000000002157.Peer-Reviewed Original ResearchConceptsNeuromuscular blocking agentsBlocking agentRapid onsetPharmacodynamic modelDifferent dose cohortsMuscle twitch heightOffset of effectSingle ascending dosePharmacokinetic/Pharmacodynamic ModelArterial plasma concentrationsIntermediate durationPlasma drug concentration dataSigmoid Emax modelDose-response studyDrug concentration dataConcentration-time dataLow interindividual variabilityDose cohortsED95 dosesAscending dosePredictable pharmacokineticsSevoflurane anesthesiaPopulation pharmacokineticsSingle dosesTwitch height
2017
Annexin 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 phosphatase
2016
Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man
Heerdt PM, Sunaga H, Owen JS, Murrell MT, Malhotra JK, Godfrey D, Steinkamp M, Savard P, Savarese JJ, Lien CA. Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man. Anesthesiology 2016, 125: 1136-1143. PMID: 27749289, DOI: 10.1097/aln.0000000000001386.Peer-Reviewed Original ResearchConceptsCardiopulmonary side effectsHistamine releaseSide effectsBlood pressureHealthy subjectsHeart rateSevoflurane/nitrous oxideDose-escalation clinical trialDynamic airway complianceNeuromuscular-blocking drugsEscalation clinical trialPlasma histamine concentrationSigmoid Emax modelClinical recoveryClinical durationAdductor pollicisTwitch depressionAirway complianceNeuromuscular blockadeClinical trialsPreclinical studiesArterial bloodEmax modelHistamine concentrationCW002
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
Comparative 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
2011
Letter to the Editor: Response to Ballestero et al
Heerdt PM. Letter to the Editor: Response to Ballestero et al. Pediatric Cardiology 2011, 32: 866-867. PMID: 21509496, DOI: 10.1007/s00246-011-9992-x.Peer-Reviewed Original ResearchNoninvasive 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 chromatographyBlockers
2009
Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure
Maslow A, Schwartz C, Mahmood F, Singh A, Heerdt PM. Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure. Journal Canadien D'anesthésie 2009, 56: 510-517. PMID: 19475470, DOI: 10.1007/s12630-009-9108-8.Peer-Reviewed Original ResearchConceptsRV myocardial tissueRV ejectionSystemic hypotensionSeptal motionParadoxical ventricular septal motionMyocardial tissueRV fractional areaVentricular septal motionEnd-organ dysfunctionRight heart failureRight ventricular failureMitral valve replacementVentricular systolic functionEarly postoperative periodSystemic organ failureSystemic organ functionSystolic septal motionMultiple inotropesVasopressor administrationVentricular failureEchocardiographic evaluationHemodynamic instabilityInotropic medicationsPostoperative periodSystolic function
2008
Practice Patterns in Choice of Left Double-Lumen Tube Size for Thoracic Surgery
Amar D, Desiderio DP, Heerdt PM, Kolker AC, Zhang H, Thaler HT. Practice Patterns in Choice of Left Double-Lumen Tube Size for Thoracic Surgery. Anesthesia & Analgesia 2008, 106: 379-383. PMID: 18227288, DOI: 10.1213/ane.0b013e3181602e41.Peer-Reviewed Original ResearchConceptsDouble-lumen tubeFr double lumen tubeLung isolationDLT repositioningThoracic surgeryDouble-lumen tube sizeSized double-lumen tubePilot studyIntraoperative outcome measuresLeft mainstem bronchusProspective pilot studyIntraoperative hypoxemiaAirway traumaTransient hypoxemiaFiberoptic bronchoscopyMainstem bronchusIntraoperative outcomesSimilar incidenceBronchial cuffDLT sizePractice patternsOutcome measuresSurgeryHypoxemiaPatients
2007
Inflammation and outcome after general thoracic surgery
Amar D, Zhang H, Park B, Heerdt PM, Fleisher M, Thaler HT. Inflammation and outcome after general thoracic surgery. European Journal Of Cardio-Thoracic Surgery 2007, 32: 431-434. PMID: 17643996, DOI: 10.1016/j.ejcts.2007.06.017.Peer-Reviewed Original ResearchConceptsC-reactive proteinMajor postoperative complicationsPostoperative complicationsIL-6Non-steroidal anti-inflammatory drug useHigh-sensitivity C-reactive proteinAnti-inflammatory drug usePreoperative C-reactive proteinSensitivity C-reactive proteinImportant postoperative complicationPreoperative albumin levelTertiary cancer centerMarkers of inflammationMarkers of outcomePostanesthesia care unitProspective data collectionGeneral thoracic surgeryLung resectionSystemic inflammationAlbumin levelsConsecutive patientsLow albuminCare unitPoor outcomeCancer Center
2006
Cardiomyopathic Etiology and SERCA2a Reverse Remodeling During Mechanical Support of the Failing Human Heart
Heerdt PM, Klotz S, Burkhoff D. Cardiomyopathic Etiology and SERCA2a Reverse Remodeling During Mechanical Support of the Failing Human Heart. Anesthesia & Analgesia 2006, 102: 32-37. PMID: 16368801, DOI: 10.1213/01.ane.0000183642.09435.ad.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAnimalsBiomechanical PhenomenaCalcium-Transporting ATPasesCardiomyopathy, DilatedConfidence IntervalsDatabases, FactualFemaleGene Expression Regulation, EnzymologicHeart-Assist DevicesHumansIn Vitro TechniquesMaleMiddle AgedRatsSarcoplasmic Reticulum Calcium-Transporting ATPasesVentricular RemodelingConceptsLeft ventricular assist deviceForce-frequency relationshipSERCA2a functionMyocardial force-frequency relationshipMyocyte calcium cyclingSERCA2a gene expressionFailing Human HeartVentricular assist deviceChronic failureProportion of trabeculaeReverse remodelingLVAD supportMyopathic originSubtype 2aDCM heartsDisease processSERCA2a mRNAAssist deviceCalcium cyclingHeart samplesAbnormal expressionMyocardial trabeculaeGene expressionMolecular remodelingHuman heart
2004
Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs
Heerdt PM, Kang R, The’ A, Hashim M, Mook RJ, Savarese JJ. Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs. Anesthesiology 2004, 100: 846-851. PMID: 15087619, DOI: 10.1097/00000542-200404000-00014.Peer-Reviewed Original ResearchConceptsX ED95Cardiopulmonary changesBolus dosingDirect myocardial depressionStable neuromuscular blockadeMean arterial pressurePlasma histamine concentrationCardiopulmonary side effectsNondepolarizing neuromuscularPulmonary vasoconstrictionArterial pressureCardiovascular effectsMyocardial depressionCardiopulmonary effectsHemodynamic measurementsInspiratory pressureNeuromuscular blockadePulmonary complianceAnesthetized dogsCardiopulmonary dataMale beaglesArterial bloodED95Heart rateSide effects
2002
Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device
Heerdt PM, Schlame M, Jehle R, Barbone A, Burkhoff D, Blanck TJ. Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device. The Annals Of Thoracic Surgery 2002, 73: 1216-1221. PMID: 11996266, DOI: 10.1016/s0003-4975(01)03621-9.Peer-Reviewed Original Research
2001
Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure
Barbone A, Holmes J, Heerdt P, The’ A, Naka Y, Joshi N, Daines M, Marks A, Oz M, Burkhoff D. Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure. Circulation 2001, 104: 670-675. PMID: 11489773, DOI: 10.1161/hc3101.093903.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedBlood PressureCalcium-Transporting ATPasesCardiac OutputFemaleFibrosisHeart FailureHeart TransplantationHeart VentriclesHeart-Assist DevicesHemodynamicsHumansIn Vitro TechniquesLungMaleMiddle AgedSarcoplasmic Reticulum Calcium-Transporting ATPasesTime FactorsVenous PressureConceptsSevere heart failureLVAD supportRight ventricleLeft ventricleReverse remodelingHeart failureHigh central venous pressurePulmonary artery diastolic pressureVentricular assist device supportLV myocyte diameterCentral venous pressureAssist device supportHigh cardiac outputHearts of patientsForce-frequency relationVentricular assist deviceComparison of rightPossible primary roleRV trabeculaeVenous pressureVentricular responseDiastolic pressureHemodynamic unloadingCardiac outputNeurohormonal factors
2000
Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure
Heerdt P, Holmes J, Cai B, Barbone A, Madigan J, Reiken S, Lee D, Oz M, Marks A, Burkhoff D. Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure. Circulation 2000, 102: 2713-2719. PMID: 11094037, DOI: 10.1161/01.cir.102.22.2713.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBlotting, NorthernBlotting, WesternCalcium-Transporting ATPasesFemaleGene Expression RegulationHeart FailureHeart VentriclesHeart-Assist DevicesHumansMaleMiddle AgedMyocardial ContractionRNA, MessengerRyanodine Receptor Calcium Release ChannelSarcolemmaSodium-Hydrogen ExchangersConceptsEnd-stage heart failureLVAD supportHeart failureContractile strengthLVAD implantationSarcoplasmic reticular membranesNegative FFRIntact myocardiumVentricular assist deviceBlot analysisExpression of genesWestern blot analysisContractile dysfunctionSERCA2a proteinLV trabeculaeSubtype 2aChronic unloadingLV tissueAssist deviceContractile forcePatientsAlters gene expressionHigher mRNAReticular membranesRyanodine receptor
1992
Inaccuracy of cardiac output by thermodilution during acute tricuspid regurgitation
Heerdt P, Pond C, Blessios G, Rosenbloom M. Inaccuracy of cardiac output by thermodilution during acute tricuspid regurgitation. The Annals Of Thoracic Surgery 1992, 53: 706-708. PMID: 1554289, DOI: 10.1016/0003-4975(92)90342-2.Peer-Reviewed Original Research