Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Silvera, Fernando; Blasina, M.F.; Vaamonde, Lucía; Tellechea, Salvador; Godoy, Carolina; Zabala, S.; Mañana, Graciela; Martell, Miguel; Olivera, Walter

doi:10.1590/s0100-879x2011007500085

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…Deleterious effect of meconium on the lung tissue in this study was confirmed also by an increased migration of polymorphonuclears, particularly neutrophils into the lung, an increased production of pro-inflammatory substances and a generation of the lung edema. In agreement with our results, higher production of the pro-inflammatory cytokines and formation of lung edema in animals with MAS were demonstrated by other authors (18,24,25), as well.…”

Section: Discussionsupporting

confidence: 94%

Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

Mokrá

Mikolka

Kosutova

et al. 2016

Acta Medica Martiniana

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Severe meconium aspiration syndrome (MAS) in the neonates often requires a ventilatory support. As a method of choice, a conventional mechanical ventilation with small tidal volumes (VT<6 ml/kg) and appropriate ventilatory pressures is used. The purpose of this study was to assess the short-term effects of the small-volume CMV performed by two neonatal ventilators: Aura V (Chirana Stara Tura a.s., Slovakia) and SLE5000 (SLE Ltd., UK) on the lung functions of rabbits with experimentally-induced MAS and to estimate whether the newly developed neonatal version of the ventilator Aura V is suitable for ventilation of the animals with MAS.In the young rabbits, a model of MAS was induced by an intratracheal instillation of a suspension of neonatal meconium (4 ml/kg, 25 mg/ml). After creating the model of MAS, the animals were ventilated with small-volume CMV (frequency 50/min, VT<6 ml/kg, inspiration time 50 %, fraction of inspired oxygen 1.0, positive end-expiratory pressure 0.5 kPa, mean airway pressure 1.1 kPa) performed by ventilator Aura V (Aura group, n=7) or ventilator SLE5000 (SLE group, n=7) for additional 4 hours. One group of animals served as healthy non-ventilated controls (n=6). Blood gases, oxygenation indexes, ventilatory pressures, lung compliance, oxygen saturation and total and differential white blood cell (WBC) count were regularly determined. After euthanizing the animals, a left lung was saline-lavaged and total and differential counts of cells in the bronchoalveolar lavage (BAL) fluid were determined. A right lung was used for estimation of lung edema formation (expressed as a wet/dry weight ratio) and for analysis of concentrations of pro-inflammatory cytokines (IL-1β, IL-8, TNF). The cytokines were measured also in the blood plasma taken at the end of experiment.Meconium instillation seriously worsened the gas exchange and induced inflammation and lung edema formation. In the Aura group, slightly lower concentrations of cytokines were found and better gas exchange early after creating the MAS model was observed. However, there were no significant differences in the respiratory parameters between the ventilated groups at the end of experiment (P>0.05).Concluding, the newly developed neonatal version of the ventilator Aura V was found to be fully comparable to widely used neonatal ventilator SLE5000. Results provided by Aura V in CMV ventilation of rabbits with meconium-induced acute lung injury suggest its great potential also for future clinical use, i.e. for ventilation of the neonates with MAS.

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Section: Discussionsupporting

confidence: 94%

Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

Mokrá

Mikolka

Kosutova

et al. 2016

Acta Medica Martiniana

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“…This is supported by the data from 5 to 7 days old piglets being subject to anesthesia with halothane and invasive blood pressure monitoring yielding values for SBP of 89 mmHg (CI 84–99) and DBP of 54 mmHg (51–60) (Voss et al, 2004). Using the thermodilution technique HI was 4.04–4.38 ± 1.23–1.42 l/min/m 2 , and the SVI 20.4/20.4 ± 5.7–9.5 ml/m 2 in 13 days old piglets (Gibson et al, 1994), and ITBI 230 ± 76 ml/m 2 in 1–3 days old piglets (Silvera et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

“…The determination of EVLWI has been performed by the thermodilution method in newborn piglets yielding a value of 20 ± 1 ml/kg (Silvera et al, 2011) and in human neonates following arterial switch operation due to transposition of the great arteries yielding 20 ± 7 ml/kg after extubation (Székely et al, 2011), however data in well babies do not exist because of the invasiveness of the technique. In (adult) humans a value of 3–7 ml/kg is considered normal, however neonates tend to have higher values because of incomplete resorption of lung fluids in the post-natal transitional process and of shunting via a patent ductus arteriosus and foramen ovale.…”

Section: Resultsmentioning

confidence: 99%

An Unsettled Promise: The Newborn Piglet Model of Neonatal Acute Respiratory Distress Syndrome (NARDS). Physiologic Data and Systematic Review

2019

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Despite great advances in mechanical ventilation and surfactant administration for the newborn infant with life-threatening respiratory failure no specific therapies are currently established to tackle major pro-inflammatory pathways. The susceptibility of the newborn infant with neonatal acute respiratory distress syndrome (NARDS) to exogenous surfactant is linked with a suppression of most of the immunologic responses by the innate immune system, however, additional corticosteroids applied in any severe pediatric lung disease with inflammatory background do not reduce morbidity or mortality and may even cause harm. Thus, the neonatal piglet model of acute lung injury serves as an excellent model to study respiratory failure and is the preferred animal model for reasons of availability, body size, similarities of porcine and human lung, robustness, and costs. In addition, similarities to the human toll-like receptor 4, the existence of intraalveolar macrophages, the sensitivity to lipopolysaccharide, and the production of nitric oxide make the piglet indispensable in anti-inflammatory research. Here we present the physiologic and immunologic data of newborn piglets from three trials involving acute lung injury secondary to repeated airway lavage (and others), mechanical ventilation, and a specific anti-inflammatory intervention via the intratracheal route using surfactant as a carrier substance. The physiologic data from many organ systems of the newborn piglet—but with preference on the lung—are presented here differentiating between baseline data from the uninjured piglet, the impact of acute lung injury on various parameters (24 h), and the follow up data after 72 h of mechanical ventilation. Data from the control group and the intervention groups are listed separately or combined. A systematic review of the newborn piglet meconium aspiration model and the repeated airway lavage model is finally presented. While many studies assessed lung injury scores, leukocyte infiltration, and protein/cytokine concentrations in bronchoalveolar fluid, a systematic approach to tackle major upstream pro-inflammatory pathways of the innate immune system is still in the fledgling stages. For the sake of newborn infants with life-threatening NARDS the newborn piglet model still is an unsettled promise offering many options to conquer neonatal physiology/immunology and to establish potent treatment modalities.

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“…This method was previously described in several published animal studies. Liet [9] previously used PiCCO2 monitoring in rabbits and other small animals [13]. The pulse-contour algorithm was also used to evaluate CO in a pediatric population, including newborns undergoing cardiac surgery [14].…”

Section: Hemodynamic Measurementsmentioning

confidence: 99%

Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion

Liu

et al. 2015

Journal of Surgical Research

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Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Cited by 7 publications

References 38 publications

Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

An Unsettled Promise: The Newborn Piglet Model of Neonatal Acute Respiratory Distress Syndrome (NARDS). Physiologic Data and Systematic Review

Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion

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