Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

Cagle, Laura A.; Franzi, Lisa M.; Linderholm, A.; Adams, Jason Y.; Harper, Richart W; Kenyon, Nicholas J.

doi:10.1371/journal.pone.0187419

Cited by 8 publications

(7 citation statements)

References 63 publications

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“…As a result, local inflammatory mediators are released and influx of neutrophils into the lung will ensue [10,42]. Our results agree with those of Cagle and colleagues, who ventilated rats for 2 hours and disclosed a larger number of neutrophils in the BALF of those ventilated with a tidal volume of 15 mL/kg than the group ventilated with 8 mL/kg [43].…”

Section: Discussionsupporting

confidence: 91%

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation

Cândido

Matos

Castro

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator-associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end-expiratory pressure (ZEEP), and normoxia ( Fi O 2 = 21 % ) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO2 and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF-α, IL-1, and IL-6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.

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Section: Discussionsupporting

confidence: 91%

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation

Cândido

Matos

Castro

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Duoxa 2/2 and Duoxa 1/1 mice were sedated as previously described (10). Positive-pressure ventilation was instituted for 4 hours using a MiniVENT (type 845; Harvard Apparatus).…”

Section: Experimental Groups and Protocolmentioning

confidence: 99%

“…Based on these observations, we hypothesized that Duoxa 2/2 mice would have reduced lung neutrophilia in a ventilator-induced acute lung injury model. resulting in less lung injury compared with Duoxa 1/1 mice (10).…”

mentioning

confidence: 95%

Role of Dual Oxidases in Ventilator-induced Lung Injury

Cagle

Linderholm

Franzi

et al. 2021

Am J Respir Cell Mol Biol

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Positive-pressure ventilation results in ventilator-induced lung injury, and few therapeutic modalities have been successful at limiting the degree of injury to the lungs. Understanding the primary drivers of ventilator-induced lung injury will aid in the development of specific treatments to ameliorate the progression of this syndrome. There are conflicting data for the role of neutrophils in acute respiratory distress syndrome pathogenesis. Here, we specifically examined the importance of neutrophils as a primary driver of ventilator-induced lung injury in a mouse model known to have impaired ability to recruit neutrophils in previous models of inflammation. We exposed Duoxa 1/1 and Duoxa 2/2 mice to lowor high-tidal volume ventilation with or without positive endexpiratory pressure (PEEP) and recruitment maneuvers for 4 hours. Absolute neutrophils in BAL fluid were significantly reduced in Duoxa 2/2 mice compared with Duoxa 1/1 mice (6.7 cells/ml; 16.4 cells/ml; P = 0.003), consistent with our hypothesis that neutrophil translocation across the capillary endothelium is reduced in the absence of DUOX1 or DUOX2 in response to ventilator-induced lung injury. Reduced lung neutrophilia was not associated with a reduction in overall lung injury in this study, suggesting that neutrophils do not play an important role in early features of acute lung injury. Surprisingly, Duoxa 2/2 mice exhibited significant hypoxemia, as measured by the arterial oxygen tension/fraction of inspired oxygen ratio and arterial oxygen content, which was out of proportion with that seen in the Duoxa 1/1 mice (141, 257, P = 0.012). These findings suggest a role for dual oxidases to limit physiologic impairment during early ventilator-induced lung injury.

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“…However, macroscopic hemorrhages, which were completely absent in PEEP-ventilated animals, depict even more severe forms of pulmonary injury. In line with this, others have previously shown protective effects of PEEP-ventilation on a histological level in mice (39), but not in the context of PV analysis. Moreover, we used the femoral vein as the injection site for hypertonic saline in our protocol, though estimation of parallel-conductance (G p ) by injecting hypertonic saline has previously been reported for the jugular vein or pulmonary artery (6, 7).…”

Section: Discussionmentioning

confidence: 53%

Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under β-Adrenergic Stimulation in Mice

Bacmeister

Segin

Medert

et al. 2019

Front. Cardiovasc. Med.

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Aim: Cardiac pressure-volume (PV loop) analysis under β-adrenergic stimulation is a powerful method to simultaneously determine intrinsic cardiac function and β-adrenergic reserve in mouse models. Despite its wide use, several key approaches of this method, which can affect murine cardiac function tremendously, have not been experimentally investigated until now. In this study, we investigate the impact of three lines of action during the complex procedure of PV loop analysis: (i) the ventilation with positive end-expiratory pressure, (ii) the time point of injecting hypertonic saline to estimate parallel-conductance, and (iii) the implications of end-systolic pressure-spikes that may arise under β-adrenergic stimulation. Methods and Results: We performed pressure-volume analysis during β-adrenergic stimulation in an open-chest protocol under Isoflurane/Buprenorphine anesthesia. Our analysis showed that (i) ventilation with 2 cmH 2 O positive end-expiratory pressure prevented exacerbation of peak inspiratory pressures subsequently protecting mice from macroscopic pulmonary bleedings. (ii) Estimations of parallel-conductance by injecting hypertonic saline prior to pressure-volume recordings induced dilated chamber dimensions as depicted by elevation of end-systolic volume (+113%), end-diastolic volume (+40%), and end-diastolic pressure (+46%). Further, using this experimental approach, the preload-independent contractility (PRSW) was significantly impaired under basal conditions (−17%) and under catecholaminergic stimulation (−14% at 8.25 ng/min Isoprenaline), the β-adrenergic reserve was alleviated, and the incidence of ectopic beats was increased >5-fold. (iii) End-systolic pressure-spikes were observed in 26% of pressure-volume recordings under stimulation with 2.475 and 8.25 ng/min Isoprenaline, which affected the analysis of maximum pressure (+11.5%), end-diastolic volume (−8%), stroke volume (−10%), and cardiac output (−11%). Conclusions: Our results (i) demonstrate the advantages of positive end-expiratory pressure ventilation in open-chest instrumented mice, (ii) underline the perils of injecting hypertonic saline prior to pressure-volume recordings to calibrate for parallel-conductance and (iii) emphasize the necessity to be aware of the consequences of end-systolic pressure-spikes during β-adrenergic stimulation.

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Effects of positive end-expiratory pressure and recruitment maneuvers in a ventilator-induced injury mouse model

Cited by 8 publications

References 63 publications

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation

Different Tidal Volumes May Jeopardize Pulmonary Redox and Inflammatory Status in Healthy Rats Undergoing Mechanical Ventilation

Role of Dual Oxidases in Ventilator-induced Lung Injury

Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under β-Adrenergic Stimulation in Mice

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