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 ResearchMeSH KeywordsAdolescentAdultBlood PressureDose-Response Relationship, DrugFemaleHeart RateHistamine ReleaseHumansIsoquinolinesMaleMiddle AgedNeuromuscular BlockadeNeuromuscular Nondepolarizing AgentsRespirationYoung AdultConceptsCardiopulmonary 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
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 chromatographyBlockersPharmacodynamics 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 dosesCW002Cysteine 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 groupDose
2006
Hemodynamic Effects of Di-Sec-Butyl Phenol, an Anesthetic Substituted Phenol
Deau J, Heerdt PM, H.S. The A, Wang Q. Hemodynamic Effects of Di-Sec-Butyl Phenol, an Anesthetic Substituted Phenol. Pharmacology 2006, 76: 117-122. PMID: 16374073, DOI: 10.1159/000090501.Peer-Reviewed Original ResearchConceptsMean blood pressureBlood pressureHeart rateHemodynamic effectsSympathetic nervous systemAge-dependent elevationHuman neuroblastoma cell lineRelease of catecholaminesSH-SY5Y cellsNeuroblastoma cell linesGanglionic blockadeNorepinephrine releaseNervous systemControl valuesYoung rabbitsCell linesElderly rabbitsRabbitsHypnosisHexamethoniumBlockadeCatecholaminesDoseRelease
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 ResearchMeSH KeywordsAnimalsBlood PressureDogsDose-Response Relationship, DrugHeart RateHistamineIsoquinolinesLungMaleNeuromuscular Nondepolarizing AgentsSpecies SpecificityTime FactorsConceptsX 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
1998
Disparity of isoflurane effects on left and right ventricular afterload and hydraulic power generation in swine.
Heerdt P, Gandhi C, Dickstein M. Disparity of isoflurane effects on left and right ventricular afterload and hydraulic power generation in swine. Anesthesia & Analgesia 1998, 87: 511-21. PMID: 9728819, DOI: 10.1097/00000539-199809000-00002.Peer-Reviewed Original ResearchConceptsPreload recruitable stroke work slopeDose-related decreaseRight ventricleLeft ventricleISO groupMinimum alveolar anesthetic concentration (MAC) isofluraneIso animalsPulmonary arterial blood flowIsoflurane-induced alterationsRight ventricular afterloadTotal arterial resistanceDose-related effectsEffects of isofluranePeak systolic pressureAutonomic nervous activityArterial blood flowGroups of swineRegional segment lengthVolatile Anesthetic EffectsEjection of bloodBiventricular contractilityRV contractilityVascular effectsVentricular afterloadSystolic pressureDisparity of Isoflurane Effects on Left and Right Ventricular Afterload and Hydraulic Power Generation in Swine
Heerdt P, Gandhi C, Dickstein M. Disparity of Isoflurane Effects on Left and Right Ventricular Afterload and Hydraulic Power Generation in Swine. Anesthesia & Analgesia 1998, 87: 511-521.. DOI: 10.1213/00000539-199809000-00002.Peer-Reviewed Original ResearchConceptsPreload recruitable stroke work slopeDose-related decreaseRight ventricleLeft ventricleISO groupMinimum alveolar anesthetic concentration (MAC) isofluraneIso animalsPulmonary arterial blood flowIsoflurane-induced alterationsTotal arterial resistanceDose-related effectsEffects of isofluranePeak systolic pressureAutonomic nervous activityArterial blood flowGroups of swineRegional segment lengthVolatile Anesthetic EffectsEjection of bloodBiventricular contractilityRV contractilityVascular effectsVentricular afterloadSystolic pressureLV afterload
1996
Nitric oxide synthesis inhibition and right ventricular systolic function in swine
Heerdt P, Pleimann B. Nitric oxide synthesis inhibition and right ventricular systolic function in swine. Journal Of Cardiothoracic And Vascular Anesthesia 1996, 10: 909-914. PMID: 8969400, DOI: 10.1016/s1053-0770(96)80055-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDose-Response Relationship, DrugNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseProspective StudiesSwineSystoleVentricular Function, RightConceptsRV end-diastolic pressureTotal arterial resistanceL-NAMERV afterloadPA elastanceArterial resistanceNitric oxide synthesis inhibitor NG-nitroNitric oxide synthesis inhibitionRight ventricular systolic functionL-arginine methyl esterMean PA pressurePulmonary arterial pressureRight ventricular contractilityVentricular systolic functionEnd-diastolic pressureIndex of contractilityPeak ejection rateUniversity animal laboratoryLarge pulmonary vesselsIndex of RVRV powerArterial pressureSystolic functionNG-nitroResistance vessels