Transient mechanical benefits of a deep inflation in the injured mouse lung

2002 ◽  
Vol 93 (5) ◽  
pp. 1709-1715 ◽  
Author(s):  
Gilman Allen ◽  
Lennart K. A. Lundblad ◽  
Polly Parsons ◽  
Jason H. T. Bates
Keyword(s):  
Recruitment Maneuver ◽  
Forced Oscillations ◽  
Mouse Lung ◽  
Positive End Expiratory Pressure ◽  
Total Recovery ◽  
Time Constants ◽  
Before And After ◽  
Injured Lung ◽  
Plateau Level ◽  
Saline Lavage

The lasting effects of a recruitment maneuver (RM) in the injured lung are not well characterized. We speculated that the reduction in respiratory elastance ( H) after a deep inflation (DI) is transient in nature and should be sustained longer at higher positive end-expiratory pressure (PEEP). Thirteen ventilated mice were given 2 DIs at various levels of PEEP before and after saline lavage. Forced oscillations were used to measure H periodically over 7 min after the DIs. Time constants (τ) were estimated for the post-DI recovery in H. Values for τ before lavage (80–115 s) were reduced after lavage (13–30 s) at all levels of PEEP ( P = 0.0001). PEEP did not significantly influence τ before or after lavage. The plateau level and total recovery in H after a DI were significantly influenced by PEEP and lavage ( P < 0.0001). Our results suggest that for a DI to be beneficial in the injured mouse lung, it may have to be applied several times a minute.

Intraoperative Recruitment Maneuver Reverses Detrimental Pneumoperitoneum-induced Respiratory Effects in Healthy Weight and Obese Patients Undergoing Laparoscopy

2010 ◽  
Vol 113 (6) ◽  
pp. 1310-1319 ◽  
Author(s):  
Emmanuel Futier ◽  
Jean-Michel Constantin ◽  
Paolo Pelosi ◽  
Gerald Chanques ◽  
Fabrice Kwiatkoskwi ◽  
...  
Keyword(s):  
Dead Space ◽  
Respiratory Mechanics ◽  
Recruitment Maneuver ◽  
Obese Patients ◽  
Healthy Weight ◽  
Positive End Expiratory Pressure ◽  
Trendelenburg Position ◽  
Before And After ◽  
Induced Changes ◽  
Reverse Trendelenburg Position

Background Pulmonary function is impaired during pneumoperitoneum mainly as a result of atelectasis formation. We studied the effects of 10 cm H2O of positive end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery. Methods Sixty consecutive adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position were prospectively studied. EELV, static elastance of the respiratory system, dead space, and gas exchange were measured before and after pneumoperitoneum insufflation with zero end-expiratory pressure, with PEEP alone, and with PEEP+RM. Results are presented as mean ± SD. Results Pneumoperitoneum reduced EELV (healthy weight, 1195 ± 405 vs. 1724 ± 774 ml; obese, 751 ± 258 vs. 886 ± 284 ml) and worsened static elastance and dead space in both groups (in all P &lt; 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P &lt; 0.01; obese, 364 ml, P &lt; 0.01) with no effect on oxygenation. Compared with PEEP alone, EELV and static elastance were further improved after RM in both groups (P &lt; 0.05), as was oxygenation (P &lt; 0.01). In all patients, RM-induced change in EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM-induced changes in EELV correlated with change in oxygenation (r = 0.42, P &lt; 0.01). Conclusion RM combined with 10 cm H2O of PEEP improved EELV, respiratory mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

scholarly journals Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration–induced Lung Injury

2012 ◽  
Vol 117 (6) ◽  
pp. 1322-1334 ◽  
Author(s):  
Aline M. Ambrosio ◽  
Rubin Luo ◽  
Denise T. Fantoni ◽  
Claudia Gutierres ◽  
Qin Lu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Recruitment Maneuver ◽  
Alveolar Wall ◽  
Arterial Oxygenation ◽  
Positive End Expiratory Pressure ◽  
Acid Aspiration ◽  
Recruitment Maneuvers ◽  
Alveolar Area

Background In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Mechanism by which positive end-expiratory pressure increases cerebrospinal fluid pressure in dogs

1982 ◽  
Vol 52 (1) ◽  
pp. 231-235 ◽  
Author(s):  
J. M. Luce ◽  
J. S. Huseby ◽  
W. Kirk ◽  
J. Butler
Keyword(s):  
Cerebrospinal Fluid ◽  
Superior Vena Cava ◽  
Subarachnoid Space ◽  
Superior Vena ◽  
Fluid Pressure ◽  
Vena Cava ◽  
Cerebrospinal Fluid Pressure ◽  
Positive End Expiratory Pressure ◽  
Arterial Blood ◽  
Before And After

We investigated possible mechanisms by which positive end-expiratory pressure (PEEP) increased cerebrospinal fluid pressure (PCSF) in anesthetized mechanically ventilated dogs. In part I of the study, PEEP was applied in 5 cmH2O increments each lasting 1–2 min, before and after a snare separated the spinal from the cerebral subarachnoid space in each animal. Next, with the spinal cord still ligated, the dogs were ventilated without PEEP while superior vena cava pressure (PSVC) was raised in 5 cmH2O increments by means of a fluid reservoir connected with the superior vena cava. Cerebrospinal fluid pressure in the cisterna magna increased immediately and in parallel with PEEP before and after the spinal subarachnoid space was occluded and also increased when PSVC was raised independently; in all circumstances the increase in PCSF correlated closely with PSVC (r = 0.926). In part II of the study, arterial blood gases were drawn before and after PEEP was applied in the same increments and for the same duration as in part I. Cerebrospinal fluid pressure measured with a hollow skull screw again rose in parallel with PEEP, whereas arterial carbon dioxide tension rose only slightly at 60 s. In part III of the study, mean arterial pressure (Pa) was allowed to decrease with PEEP or was held constant by distal aortic obstruction and volume infusion. Cerebrospinal fluid pressure increased regardless of Pa, but the increase was greater when Pa was held constant than when it fell with PEEP. We conclude that PEEP increases PCSF primarily by increasing PSVC and decreasing cerebral venous outflow. This effect is augmented if cerebral arterial inflow is increased as well.

Splanchnic and systemic absorption of intraperitoneal insulin using a new double-tracer method

1994 ◽  
Vol 266 (5) ◽  
pp. E750-E759 ◽  
Author(s):  
J. Radziuk ◽  
S. Pye ◽  
D. E. Seigler ◽  
J. S. Skyler ◽  
R. Offord ◽  
...  
Keyword(s):  
Inferior Vena Cava ◽  
Portal Vein ◽  
Inferior Vena ◽  
Vena Cava ◽  
Systemic Absorption ◽  
Tracer Method ◽  
Total Recovery ◽  
Before And After ◽  
Intraperitoneal Insulin ◽  
Serial Samples

The absorption of a bolus of intraperitoneal insulin into the splanchnic and peripheral circulations was separately assessed in dogs using an infusion of two insulin tracers (A1-[3H]insulin and B1-[3H]insulin). One tracer was infused into the superior mesenteric artery and the second into the jugular vein. Serial samples were taken before and after an injection of insulin (1 U/kg ip). Sampling was from the portal vein and the inferior vena cava. By using the principle of equivalent entry of tracer and unlabeled material, we developed two simultaneous equations for the rate of splanchnic and peripheral insulin absorption at each time point. These were solved to yield the two rates. Mean concentrations in the portal vein were approximately 25% higher than in the inferior vena cava, reflecting the splanchnic absorption. This rate accounted for almost half (51 +/- 9%) of the insulin absorbed. The remainder of the absorption was peripheral. The total recovery of intraperitoneal insulin, absorbed by either route, was 88 +/- 11%. Portal absorption peaked earlier than peripheral. Absorption by both routes was 90% complete within approximately 2 h (131 +/- 16 min). In summary, therefore, intraperitoneal insulin is rapidly and almost completely absorbed, with absorption split between the splanchnic and peripheral routes of entry.

Effects of decreasing lung compliance with oleic acid on the cardiovascular response to PEEP

1977 ◽  
Vol 233 (6) ◽  
pp. H635-H641 ◽  
Author(s):  
S. M. Scharf ◽  
R. H. Ingram
Keyword(s):  
Oleic Acid ◽  
Venous Return ◽  
Cardiovascular Response ◽  
Lung Compliance ◽  
Back Pressure ◽  
Right Atrial ◽  
Positive End Expiratory Pressure ◽  
Chest Wall Compliance ◽  
Before And After ◽  
Wall Compliance

In 12 anesthetized mongrel dogs on a constant volume ventilator, the response of the cardiovascular system to increasing positive end-expiratory pressure (PEEP) was examined before and after inducing acute lung injury with oleic acid. As PEEP was raised to approximately 16 mmHg, lung volume increased by approximately 900 ml before oleic acid and only 350 ml after. Pleural pressure increased by the same amount, indicating that both lung and chest wall compliance decreased with oleic acid. Right atrial pressure, the back pressure to venous return, also increased by the same amount. Although cardiac output at PEEP = 0 was lower after oleic acid, the relative decrements produced by increasing PEEP were the same as before oleic acid.

scholarly journals Aerosolizable Lipid Nanoparticles for Pulmonary Delivery of mRNA through Design of Experiments

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1042
Author(s):  
Hairui Zhang ◽  
Jasmim Leal ◽  
Melissa R. Soto ◽  
Hugh D. C. Smyth ◽  
Debadyuti Ghosh
Keyword(s):  
Design Of Experiments ◽  
Protein Expression ◽  
Messenger Rna ◽  
Pulmonary Delivery ◽  
Lipid Nanoparticles ◽  
In Vivo Studies ◽  
Molar Ratio ◽  
Mouse Lung ◽  
Intracellular Protein ◽  
Before And After

Messenger RNA is a class of promising nucleic acid therapeutics to treat a variety of diseases, including genetic diseases. The development of a stable and efficacious mRNA pulmonary delivery system would enable high therapeutic concentrations locally in the lungs to improve efficacy and limit potential toxicities. In this study, we employed a Design of Experiments (DOE) strategy to screen a library of lipid nanoparticle compositions to identify formulations possessing high potency both before and after aerosolization. Lipid nanoparticles (LNPs) showed stable physicochemical properties for at least 14 days of storage at 4 °C, and most formulations exhibited high encapsulation efficiencies greater than 80%. Generally, upon nebulization, LNP formulations showed increased particle size and decreased encapsulation efficiencies. An increasing molar ratio of poly-(ethylene) glycol (PEG)-lipid significantly decreased size but also intracellular protein expression of mRNA. We identified four formulations possessing higher intracellular protein expression ability in vitro even after aerosolization which were then assessed in in vivo studies. It was found that luciferase protein was predominately expressed in the mouse lung for the four lead formulations before and after nebulization. This study demonstrated that LNPs hold promise to be applied for aerosolization-mediated pulmonary mRNA delivery.

Effect of Positive End-expiratory Pressure on Regional Ventilation Distribution during Mechanical Ventilation after Surfactant Depletion

2013 ◽  
Vol 119 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Sam Bayat ◽  
Liisa Porra ◽  
Gergely Albu ◽  
Heikki Suhonen ◽  
Satu Strengell ◽  
...  
Keyword(s):  
Lung Lavage ◽  
Local Concentration ◽  
Dependent Lung ◽  
Positive End Expiratory Pressure ◽  
Regional Ventilation ◽  
Whole Lung Lavage ◽  
Functional Behavior ◽  
Before And After ◽  
Surfactant Depletion ◽  
Nondependent Lung

Abstract Background: Ventilator-induced lung injury occurs due to exaggerated local stresses, repeated collapse, and opening of terminal air spaces in poorly aerated dependent lung, and increased stretch in nondependent lung. The aim of this study was to quantify the functional behavior of peripheral lung units in whole-lung lavage-induced surfactant depletion, and to assess the effect of positive end-expiratory pressure. Methods: The authors used synchrotron imaging to measure lung aeration and regional specific ventilation at positive end-expiratory pressure of 3 and 9 cm H2O, before and after whole-lung lavage in rabbits. Respiratory mechanical parameters were measured, and helium-washout was used to assess end-expiratory lung volume. Results: Atelectatic, poorly, normally aerated, hyperinflated, and trapped regions could be identified using the imaging technique used in this study. Surfactant depletion significantly increased atelectasis (6.3 ± 3.3 [mean ± SEM]% total lung area; P = 0.04 vs. control) and poor aeration in dependent lung. Regional ventilation was distributed to poorly aerated regions with high (16.4 ± 4.4%; P &lt; 0.001), normal (20.7 ± 5.9%; P &lt; 0.001 vs. control), and low (5.7 ± 1.2%; P &lt; 0.05 vs. control) specific ventilation. Significant redistribution of ventilation to normally aerated nondependent lung regions occurred (41.0 ± 9.6%; P = 0.03 vs. control). Increasing positive end-expiratory pressure level to 9 cm H2O significantly reduced poor aeration and recruited atelectasis, but ventilation redistribution persisted (39.2 ± 9.5%; P &lt; 0.001 vs. control). Conclusions: Ventilation of poorly aerated dependent lung regions, which can promote the local concentration of mechanical stresses, was the predominant functional behavior in surfactant-depleted lung. Potential tidal recruitment of atelectatic lung regions involved a smaller fraction of the imaged lung. Significant ventilation redistribution to aerated lung regions places these at risk of increased stretch injury.

Dynamic mechanical consequences of deep inflation in mice depend on type and degree of lung injury

2004 ◽  
Vol 96 (1) ◽  
pp. 293-300 ◽  
Author(s):  
Gilman Allen ◽  
Jason H. T. Bates
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Fluid Pressure ◽  
Lavage Fluid ◽  
Forced Oscillations ◽  
Positive End Expiratory Pressure ◽  
Reduced Pressure ◽  
Volume Curve

In a previous study (Allen G, Lundblad LK, Parsons P, and Bates JH. J Appl Physiol 93: 1709-1715 , 2002), our laboratory used deep inflations (DI) in mice to show that recruitment of closed lung units can be a very transient phenomenon in lung injury. The purpose of this study was to investigate how this transience of lung recruitment depends on the nature and degree of acute lung injury. Mice were administered 50 μl of either saline ( n = 8), 0.01 M ( n = 9) or 0.025 M ( n = 8) hydrochloric acid, or 50 μg ( n = 10) or 150 μg ( n = 6) of LPS and were mechanically ventilated 24-48 h later. At various levels of positive end-expiratory pressure, two DIs were delivered, and forced oscillations were used to obtain a measure of lung stiffness ( H) periodically over 7 min. After LPS exposure, pressure-volume curve hysteresis and recovery in H after DI were no different from saline-exposed controls despite 500 times more neutrophils in bronchoalveolar lavage fluid. Pressure-volume hysteresis and recovery in H were increased in acid-exposed mice ( P < 0.001) and were correlated with bronchoalveolar lavage fluid protein content ( R = 0.81). Positive end-expiratory pressure reduced recovery in H in all groups ( P < 0.01) but reduced pressure-volume hysteresis in the acid-injured groups only ( P < 0.001). We conclude that the effects of DIs in acute lung injury depend on the degree of lung injury but only to the extent that this injury reflects a disruption of the air-liquid interface.

Sign in / Sign up

Export Citation Format

Share Document