Lung Metabolism and Inflammation during Mechanical Ventilation; An Imaging Approach

Mehrdad Pourfathi,Hooman Hamedani,Jason Ehrich,Sarmad Siddiqui,Harrilla Profka,Ian Duncan,Kai Ruppert,Stephen Kadlecek,Shampa Chatterjee,Maurizio Cereda,Rahim R Rizi,Yi Xin

doi:10.1038/s41598-018-21901-0

Mehrdad Pourfathi, Hooman Hamedani + Show 10 more

Open Access

https://doi.org/10.1038/s41598-018-21901-0

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Journal: Scientific Reports	Publication Date: Feb 23, 2018
Citations: 13	License type: open-access

Affiliation: University of Pennsylvania

Abstract

Acute respiratory distress syndrome (ARDS) is a major cause of mortality in critically ill patients. Patients are currently managed by protective ventilation and alveolar recruitment using positive-end expiratory pressure (PEEP). However, the PEEP’s effect on both pulmonary metabolism and regional inflammation is poorly understood. Here, we demonstrate the effect of PEEP on pulmonary anaerobic metabolism in mechanically ventilated injured rats, using hyperpolarized carbon-13 imaging. Pulmonary lactate-to-pyruvate ratio was measured in 21 rats; 14 rats received intratracheal instillation of hydrochloric-acid, while 7 rats received sham saline. 1 hour after acid/saline instillation, PEEP was lowered to 0 cmH2O in 7 injured rats (ZEEP group) and in all sham rats; PEEP was continued in the remaining 7 injured rats (PEEP group). Pulmonary compliance, oxygen saturation, histological injury scores, ICAM-1 expression and myeloperoxidase expression were measured. Lactate-to-pyruvate ratio progressively increased in the dependent lung during mechanical ventilation at ZEEP (p < 0.001), but remained unchanged in PEEP and sham rats. Lactate-to-pyruvate ratio was correlated with hyaline membrane deposition (r = 0.612), edema severity (r = 0.663), ICAM-1 (r = 0.782) and myeloperoxidase expressions (r = 0.817). Anaerobic pulmonary metabolism increases during lung injury progression and is contained by PEEP. Pulmonary lactate-to-pyruvate ratio may indicate in-vivo neutrophil activity due to atelectasis.

Highlights

Acute respiratory distress syndrome (ARDS) is a fatal condition that occurs in approximately 10% of patients admitted to the intensive care unit (ICU)[1], and is characterized by increased alveolar membrane permeability leading to edema, severely impaired gas exchange, hypoxemia and pulmonary neutrophilic infiltration as an innate inflammatory response[2,3]
Definition Acute respiratory distress syndrome Tidal Volume Peak inspiratory pressure Positive-end expiratory pressure Zero positiveend expiratory pressure (PEEP) Dynamic compliance, a measure of lung’s elasticity defined as (VT/(PIP-PEEP)) Fraction of inspired oxygen Collapse of the alveoli in the lungs 18F-Fluorodeoxyglocuse Positron emission tomography Hyperpolarized magnetic resonance imaging Dynamic nuclear polarization, a process to enhance the MR signal by ~10,000-fold Most abundant type of white blood cells that are recruited upon injury Myeloperoxidase, an enzyme expressed in activated neutrophils Intercellular adhesion molecule-1, a protein expressed in endothelial cells and facilitates neutrophilic recruitment The lowest part of the lungs relative to the gravity
We report the first in-vivo evidence that PEEP contains regional pulmonary anaerobic metabolism in an experimental model of lung injury (Figs 2 and 3a and Table 2)

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a fatal condition that occurs in approximately 10% of patients admitted to the intensive care unit (ICU)[1], and is characterized by increased alveolar membrane permeability leading to edema, severely impaired gas exchange, hypoxemia and pulmonary neutrophilic infiltration as an innate inflammatory response[2,3]. Definition Acute respiratory distress syndrome Tidal Volume Peak inspiratory pressure Positive-end expiratory pressure Zero PEEP Dynamic compliance, a measure of lung’s elasticity defined as (VT/(PIP-PEEP)) Fraction of inspired oxygen Collapse of the alveoli in the lungs 18F-Fluorodeoxyglocuse Positron emission tomography Hyperpolarized magnetic resonance imaging Dynamic nuclear polarization, a process to enhance the MR signal by ~10,000-fold Most abundant type of white blood cells that are recruited upon injury Myeloperoxidase, an enzyme expressed in activated neutrophils Intercellular adhesion molecule-1, a protein expressed in endothelial cells and facilitates neutrophilic recruitment The lowest part of the lungs relative to the gravity. The temporarily enhanced carbon-13 NMR signal of hyperpolarized agents (~10,000-fold) made possible by dynamic nuclear polarization (DNP)[19], provides a general molecular imaging probe capable of rapidly and noninvasively interrogating molecular pathways within minutes in animal models[18] and, more recently, in human subjects[20]

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