Animal Model Of Respiratory Failure Research Articles

Continuous negative extrathoracic pressure combined with high-frequency oscillation improves oxygenation with less impact on blood pressure than high-frequency oscillation alone in a rabbit model of surfactant depletion

BackgroundNegative air pressure ventilation has been used to maintain adequate functional residual capacity in patients with chronic muscular disease and to decrease transpulmonary pressure and improve cardiac output during right heart surgery. High-frequency oscillation (HFO) exerts beneficial effects on gas exchange in neonates with acute respiratory failure. We examined whether continuous negative extrathoracic pressure (CNEP) combined with HFO would be effective for treating acute respiratory failure in an animal model.MethodsThe effects of CNEP combined with HFO on pulmonary gas exchange and circulation were examined in a surfactant-depleted rabbit model. After induction of severe lung injury by repeated saline lung lavage, 18 adult white Japanese rabbits were randomly assigned to 3 groups: Group 1, CNEP (extra thoracic negative pressure, -10 cmH2O) with HFO (mean airway pressure (MAP), 10 cmH2O); Group 2, HFO (MAP, 10 cmH2O); and Group 3, HFO (MAP, 15 cmH2O). Physiological and blood gas data were compared among groups using analysis of variance.ResultsGroup 1 showed significantly higher oxygenation than Group 2, and the same oxygenation with significantly higher mean blood pressure compared to Group 3.ConclusionAdequate CNEP combined with HFO improves oxygenation with less impact on blood pressure than high-frequency oscillation alone in an animal model of respiratory failure.

Lung function measurements in a preterm animal model of respiratory failure: Comparison of two different neonatal ventilators

A variety of ventilators are used in the NICU. Ventilator and lung function measures are often applied in weaning protocols or as outcome variables. The effect of different ventilators on these measures has not been well studied. Our objective was to compare ventilator and lung function measurements in a chronic preterm animal model managed with two different neonatal ventilators. Timed baboon pregnancies exposed to antenatal steroids were delivered by C/S at 125 days (term = 185 days). Infants were immediately intubated, given surfactant, and ventilated with low tidal volumes (4-6 ml/kg) for 6-14 days using well-defined protocols. One group was ventilated via InfantStar (IS) and the other by VIP-Bird (VIP). Physiologic and pulmonary function data were serially recorded with the VitalTrends plethysmography system. Between ventilator comparisons were made. InfantStar (IS) was used on 22 infants in 2002-03, VIP was used on 29 infants in 2004-05. No differences were found for gestation, birth weight, gender, paO(2), paCO(2), FiO(2), arterial/alveolar ratio, dynamic compliance, inspiratory resistance, or tidal volumes. From 24 to 336 h, peak and mean airway pressure, ventilator rate, and ventilatory efficiency index (VEI: PIP x R x CO(2)/1,000) were significantly greater in the VIP group at multiple time points. VIP use was associated with a significant increase in expiratory airway resistance (Rexp - cmH(2)O/L/s) at all but one-time points studied. Compared to the IS, use of the VIP-Bird ventilator in surfactant treated immature baboons with RDS was associated with increased expiratory airway resistance and indices of impaired ventilation, but not oxygenation. Ventilator management in the NICU, especially weaning, may be affected by the specific ventilator in use.

Neutrophils and neutrophil products do not mediate pulmonary hemodynamic effects of endotoxin on oleic acid-induced lung injury.

Small-dose endotoxin (Etx) prevents pulmonary perfusion redistribution away from edematous dorsal lung regions after oleic acid (OA)-induced injury in dogs, causing a significant deterioration in oxygenation. We hypothesized that small-dose Etx might mediate this effect via polymorphonuclear neutrophil (PMN) priming with release of inflammatory mediators such as platelet activating factor (PAF) or secretory phospholipase A(2) (sPLA(2)). To test this hypothesis, we administered specific inhibitors directed against each mediator and used two strategies to generate neutropenia. PAF and sPLA(2) inhibitors were administered before OA injury, followed 2 h later by small-dose Etx (n = 4 each group). PMN depletion was achieved by hydroxyurea administration for 5 days before the study to achieve absolute neutrophil counts <1000/mm(3) (n = 4). Inhibition of PMN adherence to lung endothelium was achieved by the administration of an anti-CD18 monoclonal antibody immediately before lung injury (n = 5). Positron emission tomography was used to evaluate pulmonary perfusion distribution and lung water content. We observed no effect of these interventions on the perfusion pattern after Etx + OA. Thus, neither neutrophils nor PAF or sPLA(2) mediate the effects of Etx on the pattern of perfusion in this model of lung injury. Acute respiratory failure is characterized by severe decreases in blood oxygen. The pattern of blood flow within the lungs can contribute to this problem. This study investigated the potential role of white blood cells and their products in mediating abnormal pulmonary blood flow patterns in an experimental animal model of respiratory failure.

Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure.

To demonstrate the efficacy of partial perfluorocarbon liquid ventilation in large animal model of acute respiratory failure. Prospective, randomized, controlled trial. Animal laboratory at a university medical center. Ten adult sheep, weighing 53.0 +/- 2.8 kg. After assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death. When compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 +/- 3%; control, 55 +/- 8%; p = .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 2 +/- 8%; control, 64 +/- 5%; p = .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 +/- 0.04 mL/ cm H2O/kg; control, 0.53 +/- 0.03 mL/cm H2O/kg; p = .102). Partial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.