Paul Heerdt, PhD, MD
Research & Publications
Biography
News
Research Summary
Over the past 25+ years, the vast majority of Dr. Heerdt's research has been within 3 broad categories: a) cardiopulmonary adaptation to the stresses of anesthesia and surgery; b) evaluation of hemodynamic monitoring devices; and c) development of novel neuromuscular blocking drugs. Studies involving cardiopulmonary physiology have been conducted in both the laboratory and clinic, with an emphasis on a systems biology approach that incorporates functional and molecular aspects of adaptation. Most recently, Dr. Heerdt's laboratory has been incorporating aging and working with analytic approaches for quantifying the efficiency of mechanical coupling between the heart and circulation during acute and chronic pulmonary hypertension. Device evaluations have been largely focused upon methods for monitoring blood flow and tissue perfusion; recent studies have involved experimental models of shock. Dr. Heerdt's drug development work also involved both laboratory and clinical work, with investigation focused on a novel class of drugs that undergo “molecular inactivation” by the amino acid cysteine. This research resulted in the design and synthesis of a series of molecules that have now been licensed to pharma for further development.
Research funding and salary support have been provided by multiple foundations, industry sponsors, the Society of Cardiovascular Anesthesiologists, the American Heart Association, and the National Institutes of Health.
Coauthors
Research Interests
Cardiovascular Diseases; Heart Diseases; Chemicals and Drugs; Analytical, Diagnostic and Therapeutic Techniques and Equipment
Public Health Interests
Cardiovascular Diseases
Selected Publications
- Response to letter by Drs. Bottinger and van der HoornBerlin DA, Manoach S, Heerdt PM. Response to letter by Drs. Bottinger and van der Hoorn Intensive Care Medicine Experimental 2019, 7: 31. PMID: 31172313, PMCID: PMC6554383, DOI: 10.1186/s40635-019-0258-x.
- Glymphatic System Function in Relation to Anesthesia and Sleep StatesBenveniste 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.
- Automated expiratory ventilation assistance through a small endotracheal tube can improve venous return and cardiac outputBerlin DA, Manoach S, Oromendia C, Heerdt PM. Automated expiratory ventilation assistance through a small endotracheal tube can improve venous return and cardiac output Intensive Care Medicine Experimental 2019, 7: 6. PMID: 30627962, PMCID: PMC6326914, DOI: 10.1186/s40635-018-0217-y.
- 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.
- Blood Pressure Targets in Perioperative CareMeng L, Yu W, Wang T, Zhang L, Heerdt PM, Gelb AW. Blood Pressure Targets in Perioperative Care Hypertension 2018, 72: 806-817. PMID: 30354725, DOI: 10.1161/hypertensionaha.118.11688.
- Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy VolunteersKaullen 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.
- Perioperative pulmonary thromboembolismRuohoniemi DM, Sista AK, Doany CF, Heerdt PM. Perioperative pulmonary thromboembolism Current Opinion In Anaesthesiology 2018, 31: 75-82. PMID: 29206697, DOI: 10.1097/aco.0000000000000550.
- Accuracy of a Simulation Algorithm for Modelling LV Contractility, Diastolic Capacitance, and Energetics Using Data Available From Common Hemodynamic Monitors and EchocardiographyHeerdt 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.
- Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatasesLuo 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.
- Bridging the Educational Gap in Thoracic AnesthesiaPopescu WM, Heerdt PM. Bridging the Educational Gap in Thoracic Anesthesia Journal Of Cardiothoracic And Vascular Anesthesia 2017, 31: 1359-1360. PMID: 28800993, DOI: 10.1053/j.jvca.2017.05.021.
- Agreement of Bioreactance Cardiac Output Monitoring With Thermodilution During Hemorrhagic Shock and Resuscitation in Adult SwineBerlin 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.
- Single-lung ventilation and oxidative stressHeerdt PM, Stowe DF. Single-lung ventilation and oxidative stress Current Opinion In Anaesthesiology 2017, 30: 42-49. PMID: 27783023, DOI: 10.1097/aco.0000000000000410.
- Anesthesia for nonintubated video-assisted thoracic surgerySunaga H, Blasberg JD, Heerdt PM. Anesthesia for nonintubated video-assisted thoracic surgery Current Opinion In Anaesthesiology 2017, 30: 1-6. PMID: 27906718, DOI: 10.1097/aco.0000000000000413.
- Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in ManHeerdt 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.
- Preclinical Pharmacology of CW002Sunaga H, Savarese JJ, McGilvra JD, Heerdt PM, Belmont MR, Van Ornum SG, Murrell MT, Malhotra JK, Savard PM, Jeannotte E, Petty BJ, Allen E, Carnathan GW. Preclinical Pharmacology of CW002 Anesthesiology 2016, 125: 732-743. PMID: 27466033, DOI: 10.1097/aln.0000000000001254.
- Novel neuromuscular blocking drugs and antagonistsHeerdt PM, Sunaga H, Savarese JJ. Novel neuromuscular blocking drugs and antagonists Current Opinion In Anaesthesiology 2015, 28: 403-410. PMID: 26087274, DOI: 10.1097/aco.0000000000000209.
- 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.
- 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.
- 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.
- NHE Isoform Switching and KChIP2 Upregulation in Aging Porcine AtriaKant 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.
- Anesthesia and Pulmonary HypertensionMcGlothlin D, Ivascu N, Heerdt PM. Anesthesia and Pulmonary Hypertension Progress In Cardiovascular Diseases 2012, 55: 199-217. PMID: 23009916, DOI: 10.1016/j.pcad.2012.08.002.
- Transcriptomic analysis reveals atrial KCNE1 down‐regulation following lung lobectomyHeerdt 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.
- Letter to the Editor: Response to Ballestero et alHeerdt 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.
- Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beaglesHeerdt 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.
- Bivalirudin utilization in cardiac surgery: shifting anticoagulation from indirect to direct thrombin inhibitionAnand SX, Viles-Gonzalez JF, Mahboobi SK, Heerdt PM. Bivalirudin utilization in cardiac surgery: shifting anticoagulation from indirect to direct thrombin inhibition Journal Canadien D'anesthésie 2010, 58: 296-311. PMID: 21136312, DOI: 10.1007/s12630-010-9423-0.
- 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 011Savarese 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.
- Pharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in DogsHeerdt 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.
- Cysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in DogsSunaga 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.
- The Emerging Role of Minimally Invasive Surgical Techniques for the Treatment of Lung Malignancy in the ElderlyHeerdt PM, Park BJ. The Emerging Role of Minimally Invasive Surgical Techniques for the Treatment of Lung Malignancy in the Elderly Thoracic Surgery Clinics 2009, 19: 345-351. PMID: 20066946, DOI: 10.1016/j.thorsurg.2009.06.006.
- Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failureMaslow 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.
- Postoperative care after pulmonary resection: postanesthesia care unit versus intensive care unitPedoto A, Heerdt PM. Postoperative care after pulmonary resection: postanesthesia care unit versus intensive care unit Current Opinion In Anaesthesiology 2009, 22: 50. PMID: 19295292, DOI: 10.1097/aco.0b013e32831d7b25.
- In Response:Amar D, Heerdt PM, Desiderio DP, Kolker AC. In Response: Anesthesia & Analgesia 2008, 107: 1082. PMID: 18713935, DOI: 10.1213/ane.0b013e3181865e5c.
- The Emerging Role of Minimally Invasive Surgical Techniques for the Treatment of Lung Malignancy in the ElderlyHeerdt 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.
- Activation of brain protein phosphatase‐1I following cardiac arrest and resuscitation involving an interaction with 14‐3‐3γPlatholi J, Heerdt PM, Tung H, Hemmings HC. Activation of brain protein phosphatase‐1I following cardiac arrest and resuscitation involving an interaction with 14‐3‐3γ Journal Of Neurochemistry 2008, 105: 2029-2038. PMID: 18284617, PMCID: PMC3872065, DOI: 10.1111/j.1471-4159.2008.05300.x.
- Practice Patterns in Choice of Left Double-Lumen Tube Size for Thoracic SurgeryAmar 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.
- Protein phosphatase-2A is activated in pig brain following cardiac arrest and resuscitationZhang TT, Platholi J, Heerdt PM, Hemmings HC, Tung HY. Protein phosphatase-2A is activated in pig brain following cardiac arrest and resuscitation Metabolic Brain Disease 2008, 23: 95-104. PMID: 18197471, DOI: 10.1007/s11011-007-9074-1.
- Nitrosative Stress and Myocardial Sarcoplasmic Endoreticular Calcium Adenosine Triphosphatase Subtype 2a Activity after Lung Resection in SwineHeerdt PM, Lane P, Pan BY, Schaefer U, Crabtree M, Hong R, Singer AA, Levi R, Park BJ. Nitrosative Stress and Myocardial Sarcoplasmic Endoreticular Calcium Adenosine Triphosphatase Subtype 2a Activity after Lung Resection in Swine Anesthesiology 2007, 107: 954-962. PMID: 18043064, DOI: 10.1097/01.anes.0000291446.70921.61.
- Inflammation and outcome after general thoracic surgeryAmar 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.
- Differential regulation of protein phosphatase-1I by neurabinBullock SA, Platholi J, Gjyrezi A, Heerdt PM, Tung HY, Hemmings HC. Differential regulation of protein phosphatase-1I by neurabin Biochemical And Biophysical Research Communications 2007, 358: 140-144. PMID: 17467665, PMCID: PMC1989152, DOI: 10.1016/j.bbrc.2007.04.076.
- Pulmonary resection in the elderlyCastillo MD, Heerdt PM. Pulmonary resection in the elderly Current Opinion In Anaesthesiology 2007, 20: 4-9. PMID: 17211159, DOI: 10.1097/aco.0b013e32801271fa.
- Systemic oxidative stress associated with lung resection during single lung ventilationHeerdt PM, Lane PB, Crabtree MJ, Park BJ. Systemic oxidative stress associated with lung resection during single lung ventilation European Journal Of Cardio-Thoracic Surgery 2006, 30: 568-569. PMID: 16857372, DOI: 10.1016/j.ejcts.2006.05.022.
- Hemodynamic Effects of Di-Sec-Butyl Phenol, an Anesthetic Substituted PhenolDeau 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.
- Cardiomyopathic Etiology and SERCA2a Reverse Remodeling During Mechanical Support of the Failing Human HeartHeerdt 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.
- Anesthetic-Induced Alteration in Expression of Myocardial Calcium Cycling ProteinsHeerdt PM, H.S. The A, Markov NP. Anesthetic-Induced Alteration in Expression of Myocardial Calcium Cycling Proteins Journal Of Cardiothoracic And Vascular Anesthesia 2005, 19: 340-344. PMID: 16130061, DOI: 10.1053/j.jvca.2005.02.007.
- Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in DogsHeerdt 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.
- Disease-specific remodeling of cardiac mitochondria after a left ventricular assist deviceHeerdt 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.