Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction

Miller, Thomas L.; Singhaus, Clifford J.; Sherman, Tami Irwin; Greenspan, Jay S.; Shaffer, Thomas H.

doi:10.1097/01.pcc.0000200942.23574.ca

Cited by 8 publications

(10 citation statements)

References 18 publications

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“…Nonetheless, we contend that the anatomy is similar enough to study physiologic mechanisms, and the piglet as model for treatment of lung injury has been well established. 4,22 …”

Section: Discussionmentioning

confidence: 99%

High‐flow nasal cannula: Impact on oxygenation and ventilation in an acute lung injury model

Frizzola

Miller

Rodríguez

et al. 2010

Pediatric Pulmonology

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207

144

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SUMMARY Introduction High-flow nasal cannula therapy (HFNC) has been shown to be more effective than continuous positive airway pressure (CPAP) in reducing intubations and ventilator days. HFNC likely provides mechanisms to support respiratory efficiency beyond application of distending pressure. We reason that HFNC washout of nasopharyngeal dead space impacts CO2 removal along with oxygenation. The aim of this study was to demonstrate the flow dependence of CO2 reduction and improved oxygenation during HFNC and the dependence on leak around the nasal prongs. Materials and Methods Neonatal piglets (n=13; 2-6kg) were injured with IV oleic acid and supported with HFNC at 2 through 8 L/minute. High and low leak around the nasal prongs was accomplished by using single and double prong cannulae, respectively. Measurement of hemodynamic, respiratory and blood gas parameters were made at each setting following 10 minutes for physiologic equilibration. Tracheal pressures were recorded by transmural catheters. Results With HFNC, CO2 trended downward in a flow dependent manner independent of leak. Oxygenation and tracheal pressures increased in a flow dependent manner with the greatest effect during double prong. At 8L/minute, tracheal pressures did not exceed 6±1 cmH2O. Conclusions HFNC improves gas exchange in a flow dependent manner; double prong had greater impact on O2; single prong had greater impact on CO2 elimination.

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“…Nonetheless, we contend that the anatomy is similar enough to study physiologic mechanisms, and the piglet as model for treatment of lung injury has been well established. 4,22 …”

Section: Discussionmentioning

confidence: 99%

High‐flow nasal cannula: Impact on oxygenation and ventilation in an acute lung injury model

Frizzola

Miller

Rodríguez

et al. 2010

Pediatric Pulmonology

Self Cite

207

144

View full text Add to dashboard Cite

show abstract

“…Piglets were anesthetized initially with two 1 mL/kg intramuscular injections, separated by 10 min, of an anesthesia cocktail (ketamine: 23 mg/kg; acepromazine: 0.58 mg/kg; xylazine: 0.8 mg/kg [KAX]) adapted from previously described piglet protocols [30, 38]. Local anesthesia was delivered to the skin and soft tissues around the surgical sites with 0.5% lidocaine HCl (4 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…Decay in the elevated resistance was compensated with an infusion of 1 mg/kg/hr of bethanechol chloride started through the venous line following the initial bolus. This dosing regimen was adapted from a previously described piglet protocol [30]. To compare the two methodologies described herein, we were interested in establishing a large range of pulmonary changes (baseline to maximum dose response without evoking significant cardiovascular changes) instead of a standard dose response assessment with small pulmonary changes.…”

Section: Methodsmentioning

confidence: 99%

“…The clinical applicability of the neonatal piglet model has been extensively studied for developmental respiratory biological processes and pre-clinical endpoints by our group [30] as well as numerous other investigators [31–37]. However, to validate this methodology for broad clinical use, we believe that accurate in vivo testing (a neonatal animal model) of an airway challenge is warranted.…”

Section: Introductionmentioning

confidence: 99%

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Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques

et al. 2013

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The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). The present study represents a preclinical animal study to determine whether these respiratory function techniques (LMS and IOS) are comparable in detecting changes in respiratory resistance derived from a direct pharmacological challenge.

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“…12 Juvenile pigs were chosen because of their comparable size to pediatric patients and because of their previous application in pediatric pulmonary research. 13,14 The methodology was designed to closely mimic the clinical scenario typical for OLV procedures such that the study would have more clinical relevance. This study was approved by the Institutional Animal Care and Use Committee, Department of Biomedical Research, Nemours, in accordance with the National Institutes of Health guidelines.…”

Section: Methodsmentioning

confidence: 99%

Hyperoxia during one lung ventilation: Inflammatory and oxidative responses

Fisher

Husain

Wolfson

et al. 2012

Pediatric Pulmonology

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Summary Background It is common practice during one lung ventilation (OLV) to use 100% oxygen, although this may cause hyperoxia- and oxidative stress-related lung injury. We hypothesized that lower oxygen (FiO2) during OLV will result in less inflammatory and oxidative lung injury and improved lung function. Methods Twenty pigs (8.88 ± 0.84 kg; 38 ± 4.6 days) were assigned to either the hyperoxia group (n = 10; FiO2 = 100%) or the normoxia group (n = 10; FiO2 < 50%). Both groups were subjected to 3 hr of OLV. Blood samples were tested for pro-inflammatory cytokines and lung tissue was tested for these cytokines and oxidative biomarkers. Results There were no differences between groups for partial pressure of CO2, tidal volume, end-tidal CO2, plasma cytokines, or respiratory compliance. Total respiratory resistance was greater in the hyperoxia group (P = 0.02). There were higher levels of TNF-α, IL-1β, and IL-6 in the lung homogenates of the hyperoxia group than in the normoxia group (P ≤ 0.01, 0.001, and 0.001, respectively). Myeloperoxidase and protein carbonyls (PC) were higher (P = 0.03 and P = 0.01, respectively) and superoxide dismutase (SOD) was lower in the lung homogenates of the hyperoxia group (P ≤ 0.001). Conclusion Higher myeloperoxidase, PC, and cytokine levels, and lower SOD availability indicate a greater degree of injury in the lungs of the hyperoxia animals, possibly from using 100% oxygen. In this translational study using a pig model, FiO2 ≤ 50% during OLV reduced hyperoxic injury and improved function in the lungs.

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Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction

Abstract: The INOvent was effective for controlling heliox delivery of iNO. Despite marked reduction in respiratory resistance with heliox gas ventilation in a neonatal model of pharmacologic bronchoconstriction, nitrox might perform better as a delivery vehicle for iNO.

Cited by 8 publications

References 18 publications

High‐flow nasal cannula: Impact on oxygenation and ventilation in an acute lung injury model

High‐flow nasal cannula: Impact on oxygenation and ventilation in an acute lung injury model

Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques

Hyperoxia during one lung ventilation: Inflammatory and oxidative responses

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