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
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
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
2010
Pharmacodynamics 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 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
2000
Isoflurane Pretreatment Ameliorates Postischemic Neurologic Dysfunction and Preserves Hippocampal Ca2+/Calmodulin-dependent Protein Kinase in a Canine Cardiac Arrest Model
Blanck T, Haile M, Xu F, Zhang J, Heerdt P, Veselis R, Beckman J, Kang R, Adamo A, Hemmings H. Isoflurane Pretreatment Ameliorates Postischemic Neurologic Dysfunction and Preserves Hippocampal Ca2+/Calmodulin-dependent Protein Kinase in a Canine Cardiac Arrest Model. Anesthesiology 2000, 93: 1285-1293. PMID: 11046218, DOI: 10.1097/00000542-200011000-00023.Peer-Reviewed Original ResearchMeSH KeywordsAnesthetics, InhalationAnimalsBlood PressureBlotting, WesternBrain DiseasesCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesDogsFemaleHeart Arrest, InducedHeart RateHippocampusIschemic Attack, TransientIschemic PreconditioningIsofluraneNeuroprotective AgentsSynaptosomesConceptsNeurologic deficit scoreCanine cardiac arrest modelCardiac arrest modelDeficit scoresIschemic animalsCardiac arrestGlobal ischemiaStriatum of animalsEffective neuroprotective drugsIsoflurane pretreatmentNeurologic dysfunctionNeurologic functionHippocampal contentNeuroprotective effectsIsoflurane exposureHippocampal levelsIntensive careNeuroprotective drugsRat modelVentricular fibrillationInhalational anestheticsTreatment groupsBlinded evaluatorsCanine modelIschemia