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The Research

Lung Physiology & Micromechanics

Mechanism of Lung Expansion: A review. Resp Care 1983.

The Alveolar recruitment-derecruitment is the primary mechanism by which lung volume changes during mechanical ventilation. Surgical Forum 1998.

Videomicroscopy provides accurate in vivo assessment of pulmonary microvascular reactivity in rabbits. Shock 1999.

The Mechanism of Lung Volume Change during Mechanical Ventilation. Am J Resp Crit Care Med 1999.

Multiple sequential insults cause post-pump syndrome. Ann Thorac Surg 1999.

Soluble tumor necrosis factor receptor prevents post-pump syndromes. J Surg Res 1999.

Matrix Metalloproteinase Inhibitor Prevents Acute Lung Injury after Cardiopulmonary Bypass. Circulation 1999.

Alveolar recruitment as a mechanism of normal lung volume change: evidence from a novel nuclear imaging technique. Surgical Forum 1999.

Altered alveolar mechanics in the acutely injured lung. Crit Care Med 2001.

Visual validation of the mechanical stabilizing effects of PEEP at the alveolar level (Mechanical Stabilizing effects of PEEP). J Surg Res 2001.

Stabilizing Alveoli With Positive End-Expiratory Pressure (PEEP) Reduces Lung Injury. Surgical Forum 2001.

Alveolar mechanics alter hypoxic pulmonary vasoconstriction. Crit Care Med 2002.

Tidal volume increase do not affect alveolar mechanics in normal lung but cause alveolar over-distension and exacerbate alveolar instability following surfactant deactivation. Crit Care Med 2002.

Positive end-expiratory pressure (PEEP) after a recruitment maneuver prevents both alveolar collapse and recruitment/derecruitment. Am J Resp Crit Care Med 2003.

Alveolar inflation during generation of a quasi-static pressure/volume curve in the acutely injured lung. Crit Care Med 2003.

Alveolar instability causes early ventilator-induced lung injury independent of neutrophils. Am J Resp Crit Care Med 2004.

Alveolar Mechanics in the Acutely Injured Lung: Role of Alveolar Instability in the Pathogenesis of VILI. Resp Care 2004.

Dynamic alveolar mechanics and ventilator induced lung injury (VILI). Crit Care Medicine 2005.

Pulmonary impedance and alveolar instability during injurious ventilation in rats. J Appl Physiol 2005.

Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med 2006.

Absence of Alveolar Tears in Rat Lungs with Significant Alveolar Instability. Respiration. 2007.

Alveolar instability caused by mechanical ventilation initially damages the nondependent normal lung. Crit Care 2007.

Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics. Crit Care 2007.

Using the pressure volume (P/V) curve to set proper PEEP in acute lung injury. Nurs Crit Care 2007.

Effect of Positive End-expiratory Pressure (PEEP) and Tidal Volume on Alveolar Instability-Induced Lung Injury. Crit Care 2007.

Correlation of alveolar recruitment-derecruitment with inflection points on the pressure-volume curve. Intensive Care Med. 2007;33:1204-1211.

An official ATS Conference Proceedings: Advances in small-animal imaging application to lung pathophysiology. Proc Am Thorac Soc 2008.

The role of time and pressure on alveolar recruitment. J Appl Physiol 2009.

Dynamic alveolar mechanics in acute lung injury. Crit Care Med 2010.

Alveolar Mechanics and other Great Mysteries. J Appl Physiol 2012.

Lung recruitment: the combined effect ‘North’ and ‘South’ of the diaphragm. Crit Care Med 2012.

Commentaries on Viewpoint: Unresolved mysteries. J Appl Physiol 2012.

Mechanical breath profile of APRV minimizes micro-strain in acute lung injury. JAMA Surg 2014.

Airway pressure release ventilation (APRV) reduced conducting airway micro-Strain in lung injury. J Am Coll Surg 2014.

Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation. Am J Physiol Lung Cell Mol Physiol 2014.

Response to letter by Dr. M.S.A. Mohamed (Antagonizing reactive oxygen species during lung perfusion). Am J Physiol Lung Cell Mol Physiol 2014.

Predicting the response of the injured lung to the mechanical breath profile. J Apply Physiol 2015.

Alveolar instability (atelectrauma) is not identified by arterial oxygenation predisposing the development of an occult ventilator-induced lung injury. Intensive Care Med Exp 2015.

Effect of airwary pressure release ventilation on dynamic alveolar heterogeneity. JAMA Surg 2015.

Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury. J Appl Physiol 2017.

Reply to Drs. Monjezi and Jamaati: Dynamic alveolar mechanics are more than a soap bubble on a capillary tube. J Appl Physiol 2018.

Mechanical Ventilation Lessons Learned from Alveolar Micromechanics. Front Physiol 2020.

The POOR Get POORer: A Hypothesis for the Pathogenesis of Ventilator-induced Lung Injury. Am J Resp Crit Care Med 2020.

Atelectrauma versus Volutrauma: A Tale of Two Time-Constants. Crit Care Explorations. 2020;1-9.

Assessment of Heterogeneity in Lung Structure and Function During Mechanical Ventilation: A Review of Methodologies. J of Med Diagn. Apr 2022. [PMID: 35832339]

Protective Ventilation in a Pig Model of Acute Lung Injury: Timing is as Important as Pressure. J Appl Physiol. Nov 2022. 133(5):1093-105. [PMID: 36135956]

Sustained vs. Intratidal Recruitment in the Injured Lung During Airway Pressure Release Ventilation: A Computational Modeling Perspective. Mil Med. Dec 2023. 18; S6:141-8. [PMID: 37948236]

Atelectrauma can be avoided if expiration is sufficiently brief: evidence from inverse modeling and oscillometry during airway pressure release ventilation. Crit Care. Oct 2024. 28:329. [PMID: 39380082]

Sepsis, Trauma & Inflammation

Peritoneal negative pressure therapy prevents multiple organ injury in a chronic porcine sepsis and ischemia/reperfusion model. Shock 2010.

A clinically applicable porcine model of septic and ischemia/reperfusion induced shock and multiple organ injury. J Surg Res 2011.

Sepsis: Something Old, Something New, and a Systems View. J Crit Care 2011.

Lung injury induced by sepsis: lessons learned from large animal models and future directions for treatment. Expert Rev Anti Infect Ther 2011.

A two-compartment mathematical model of endotoxin-induced inflammatory and physiologic alterations in swine. Crit Care Med 2012.

Linking Inflammation and Cardiorespiratory Variability in Sepsis via Computational Modeling. Front Physiol 2012.

Toward computational identification of multiscale ‘Tipping Points’ in acute inflammation and multiple organ failure. Ann Biomed Eng 2012.

Computational and Systems Biology in Trauma and Sepsis: Current and Future Perspectives. International J Burns Trauma 2012.

Removal of inflammatory ascites is associated with dynamic modification of local and systemic inflammation along with prevention of acute lung injury: In Vivo and In Silico studies. Shock 2014.

Trauma in silico: Individual-specific mathematical models and virtual clinical populations. Science Translational Medicine 2015.

Onset of inflammation with ischemia: Implications for donor lung preservation and transplant survival. Am J Transplant 2016.

Hemostatic shape memory polymer foams with improved survival in a lethal traumatic hemorrhage model. Acta Biomateri. 2022;137:112-123. [PMID: 34655799]

Vanillic Acid-based Pro-coagulant Hemostatic Shape Memory Polymer Foams with Antimicrobial Properties against Drug-resistant Bacteria. Acta Biomaterialia. Nov 2024. 189:254-269. [PMID: 39343289.]

Curcumin

(COL-3/CMT-3)

A Role for the Anti-Inflammatory Properties of Tetracyclines in the Prevention of Acute Lung Injury. Current Medicinal Chemistry 2001.

Chemically-modified tetracycline (COL-3) prevents the development of septic shock and acute respiratory distress syndrome in a clinically applicable porcine model. Shock 2005.

Can systemic diseases co-induce (NOT just exacerbate) periodontitis? A hypothetical “two-hit” model. J Dent Res 2006.

Chemically-Modified Tetracycline Improves Contractility in Porcine Coronary Ischemia/Reperfusion Injury. J Cardiac Surgery 2006.

Chemically modified tetracycline (COL-3) improves survival if given 12 but 24 hours after cecal ligation and puncture. Shock 2006.

Jack of All Trades: Pleiotropy and the application of Chemically Modified Tetracycline -3 in Sepsis and the Acute Respiratory Distress Syndrome (ARDS). Pharmacological Research. 2011.

Chemically Modified Tetracycline-3 prevents ARDS in a Porcine Model of Sepsis+ Ischemia/reperfusion induced lung injury. Shock 2012.

Impact of chemically-modified tetracycline-3 on intertwined physiological, biochemical, and inflammatory networks in porcine sepsis/ARDS. Int J Burn Trauma 2015.

Differential susceptibility of human SP-B genetic variants on lung injury caused by bacterial pneumonia and the effect of a chemically modified curcumin. Shock 2016.

Nano-chemically modified tetracycline-3 (nCMT-3) attenuates acute lung injury via blocking sTREM-1 release and NLRP3 inflammasome activation. Shock. May 2022. 57(5):749-58. [PMID: 35583915]

Prophylactic nCMT-3 Attenuates Sepsis-Induced Acute Kidney Injury (AKI) by Blocking NLRP3 Inflammasome Activation and Apoptosis. Shock. June 2023. 59(6):922-9. [PMID: 36939682]

Time-Controlled Adaptive Ventilation (APRV)

Ventilator strategies for posttraumatic acute respiratory distress sydnrome: airway pressure release ventilation and the role of spontaneous breathing in critically ill patients. Curr Opin Crit Care 2004.

Other approaches to open-lung ventilation: Airway pressure release ventilation. Crit Care Med 2005.

Airway Pressure Release Ventilation: A boost for spontaneous breathing. Am Nurse Today 2006.

Early stabilizing ventilation prevents acute respiratory distress syndrome: A novel timing-based ventilatory intervention to avert lung injury. J Trauma Acute Care Surg 2012.

Up in smoke: Airway pressure release ventilation must be applied correctly to protect the lung. Crit Care Med 2012.

Early airway pressure release ventilation prevents ARDS: A novel preventive approach to lung injury. Shock 2013.

Airway pressure release ventilation prevents ventilator induced lung injury in normal lungs. JAMA Surg 2013.

Preemptive application of airway pressure release ventilation (APRV) prevents development of acute respiratory distress syndrome (ARDS) in a rat traumatic hemorrhagic shock model. Shock 2013.

Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: A systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg 2013.

Mechanical breath profile of APRV minimizes micro-strain in acute lung injury. JAMA Surg 2014.

Airway pressure release ventilation (APRV) reduced conducting airway micro-Strain in lung injury. J Am Coll Surg 2014.

Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence. CHEST 2015.

Effect of airwary pressure release ventilation on dynamic alveolar heterogeneity. JAMA Surg 2015.

Reducing ARDS Occurrence using Mechanical Ventilation. World J Respirology 2015.

The Effects of Airway Pressure Release Ventilation on Respiratory Mechanics in an Extrapulmonary ARDS Model. Intensive Care Med Exp 2015.

Preemptive Mechanical Ventilation Can Block Progressive Acute Lung Injury. World J Resp Crit Care Med 2016.

The 30-year evolution of airway pressure release ventilation (APRV). Intensive Care Med Exp 2016.

Limiting ventilator associated lung injury in a pre-term porcine neonatal model. J Ped Surg 2017.

Biological response to time-controlled adaptive ventilation depends on acute respiratory distress syndrome etiology. Crit Care Med 2018.

Preemptive mechanical ventilation based on dynamic physiology in the alveolar micro-environment: Novel considerations of time-dependent properties of the respiratory system. J Tr Acute Care Surg 2018.

The time-controlled adaptive ventilation (TCAV) Protocol: Mechanistic approach to reducing VILI. European Resp Review 2019.

Time-controlled ventilation (TCAV) accelerates simulated mucus clearance via increased expiratory flow rate. Intensive Care Med Exp 2019.

A physiologically informed strategy to effectively open, stabilize, and protect the acutely injured lung. Front Physiol 2020.

Prevention and Treatment of Acute Lung Injury with Time-Controlled Adaptive Ventilation: Physiologically Informed Modification of Airway Pressure Release Ventilation. Ann Int Care 2020.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection. Respir Res. Jan 2024. 18;25(1):37. [PMID: 38238778]

VILI & ARDS

Severity of injury is underestimated in the absence of autopsy verifications. J Trauma 2004.

The development of acute respiratory distress syndrome model after gut ischemia/reperfusion injury followed by fecal peritonitis in pigs: A clinically relevant model. Shock 2005.

Can ventilator mode reduce ventilator induced lung injury (VILI)? Crit Care Med 2006.

Titration of Mean Airway Pressure and FiO2 During High Frequency Oscillatory Ventilation in a Porcine Model of Acute Lung Injury. J Surg Res 2010.

Comparison of "open lung" models with low tidal volumes in a porcine lung injury model. J Surg Res 2011.

Lung injury induced by sepsis: lessons learned from large animal models and future directions for treatment. Expert Rev Anti Infect Ther 2011.

Bayesian inference of the lung alveolar septal model for the identification of alveolar mechanics associated with acute respiratory distress syndrome. Phys Biol 2013.

Commentaries on Viewpoint: The ongoing need for good physiological investigation: Obstructive sleep apnea in HIV patients as a paradigm. J Appl Physiol 2015.

The impact of mechanical ventilation on the pathophysiology of progressive acute lung injury. J Appl Physiol 2015.

ARDS: what experimental models have taught us. Intensive Care Med 2016.

“Open the lung and keep it open”: a homogeneously ventilated lung is a ‘healthy lung’. Ann Transl Med 2016.

Lung stress, strain and energy load – Engineering concepts to understand the mechanism of ventilator induced lung injury (VILI). Intensive Care Med Exp.

Purinergic signaling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury. Purinergic Signal 2017.

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model. Intensive Care Med Exp 2017.

Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI). Intensive Care Med Exp 2017.

Looking beyond macroventilatory parameters and rethinking ventilator-induced lung injury. J Appl Physiol. 2018;124:1220.

Excessive extracellular ATP desensitizes P2Y2 and P2X4 STP receptors provoking surfactant impairment ending in ventilation-induced lung injury. Int J Mol Sci 2018.

Last Word on Veiwpoint: Looking beyond macroventilatory parameters and rethinking ventilator-induced lung injury. J Appl Physiol 2018.

Acute lung injury: How to stabilize a broken lung. Crit Care 2018.

Never give the lung the opportunity to collapse.Trends in Anaesthesia and Crit Care 2018.

A Ventilator Cannot Set Itself nor can it be Solely Responsible for Outcomes. Crit Care Med. Apr 2022. 50(4):695-9. [PMID: 35311779]

Unshrinking the Baby Lung to Calm the VILI Vortex. Crit Care. Aug 2022. 26(1):242. [PMID: 35934707]

Ventilator-Induced Lung Injury as a Dynamic Balance Between Epithelial Cell Damage and Recovery. ABME. Mar 2023. [PMID: 37000319]

Mechanical Power and Ventilator-Induced Lung Injury: What Does Physics Have to Say? Am J Resp Crit Care Med. Sep 2023. [PMID: 37729623]

Neonatal

Limiting ventilator associated lung injury in a pre-term porcine neonatal model. J Ped Surg 2017.

Enteral administration of bacteria fermented formula in newborn piglets: A high fidelity model of necrotizing enterocolitis (NEC) PLoS One. 2018.

Mechanical Ventilation in Pediatric and Neonatal Patients. Frontiers in Physiology. Mar 2022. [PMID: 35369685]

Ratchet Recruitment in the Acute Respiratory Distress Syndrome: Lessons Learned from the Newborn Cry. Frontiers in Physiology. November 2023. 1-6. [PMID: 28028774]

Meconium Influences Pulmonary Short-Chain Fatty Acid Concentration in Porcine Meconium Aspiration Model. Biomedicine Hub. Dec 2024. Accepted.

Chest Wall Elastance and Intra-Abdominal Hypertension

Loss of airway pressure during HFOV results in an extended loss of oxygenation: A retrospective animal study, Journal of Surgical Research. 2009 162(2):250-7.

Plateau and transpulmonary pressure with elevated intra-abdominal pressure or atelectasis. J Surg Res. 2010; 149(1): 17-24.

Peritoneal negative pressure therapy prevents multiple organ injury in a chronic porcine sepsis and ischemia/reperfusion model. Shock. 2010; 34(5):525-534.

The Effects of Airway Pressure Release Ventilation on Respiratory Mechanics in an Extrapulmonary ARDS Model. Intensive Care Med Exp 2015.

Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation. Resp Care. Feb 2024. [PMID: 38408775]

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