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Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation
Published on: June 30, 2014
Effects of meconium aspiration in isolated perfused rat lungs
Wlodzimierz M Wisniewski1, Alexander M Zagariya, Narendra Pavuluri
1Division of Neonatology, Department of Pediatrics, University of Illinois, Chicago, Illinois 60616, USA.
Abstract:
Our objective was to study meconium-induced lung injury in isolated perfused rat lungs exposed to anoxia. Our working hypothesis was that meconium-induced lung injury is independent of preexisting hypoxia, and that hypoxia will increase severity of lung injury observed after meconium aspiration. We compared five different groups of animals (n = 5) for pulmonary arterial pressure (PAP), weight lung changes, and TNFalpha expression. Group I had lungs instilled with 4 ml of normal saline. Group II had lungs exposed to 5 min of anoxia. Group III had lungs instilled with 4 ml of 30% filtered human meconium. Group IV had lungs exposed to 5 min of anoxia and then instilled with 4 ml of 30% filtered human meconium. Group V had lungs instilled with 4 ml of 30% unfiltered human meconium. Our subjects were adult Sprague-Dawley rats. The isolated rat lung model was prepared according to Levey and Gast (J Appl Physiol 1966;21:313-316). Lungs were ventilated with room air. Anoxia was caused by the use of N(2). The pulmonary artery was cannulated, and pulmonary arterial pressure and lung weight were measured. Lung weight and pulmonary arterial pressure were monitored for 120 min, and TNFalpha levels were measured in effluent at 15, 30, 60, and 120 min. Experiments were done at the Michael Reese Hospital (Chicago, IL). At the end of the experiment, PAP reached its highest values in group V (10.0 +/- 1.7 mmHg). Final PAPs in groups I-IV were: 4.85 +/- 0.3, 4.99 +/- 0.4, 5.93 +/- 0.3, and 7.25 +/- 0.51 mmHg, respectively). Lung wet weight increased significantly only in groups IV and V vs. group I; at 120 min, they were: 0.96 +/- 0.3 g, P < 0.01, and 1.5 g +/- 0.2 g, P < 0.01, respectively. TNFalpha levels did not change significantly over time in group I. TNFalpha is a marker as well as proprietor of pulmonary inflammatory response. TNFalpha reached its highest levels in groups IV and V: 595 and 753 pg/ml at 120 min, respectively. In conclusion, a short episode of anoxia prior to meconium aspiration may increase lung sensitivity to meconium-induced lung injury. This effect may be moderated by the TNFalpha present in the pulmonary circulation.
Insights
A short period of anoxia before meconium aspiration may worsen lung injury. Hypoxia increases lung sensitivity to meconium, potentially moderated by tumor necrosis factor-alpha (TNFalpha) levels.
Area of Science:
- Pulmonary Medicine
- Neonatal Physiology
Background:
- Meconium aspiration syndrome (MAS) is a significant cause of neonatal respiratory distress.
- The role of hypoxia in exacerbating meconium-induced lung injury is not fully understood.
Purpose of the Study:
- To investigate the effect of anoxia on meconium-induced lung injury in an isolated perfused rat lung model.
- To determine if pre-existing hypoxia increases the severity of lung injury following meconium aspiration.
Main Methods:
- Isolated perfused rat lungs were divided into five groups: saline control, anoxia only, filtered meconium, anoxia followed by filtered meconium, and unfiltered meconium.
- Pulmonary arterial pressure (PAP), lung weight changes, and tumor necrosis factor-alpha (TNFalpha) levels were measured over 120 minutes.
Main Results:
- Anoxia followed by meconium aspiration (Groups IV and V) led to significant increases in PAP and lung weight compared to controls.
- Highest PAP and lung weight increases were observed with unfiltered meconium after anoxia (Group V).
- TNFalpha levels, a marker of pulmonary inflammation, were significantly elevated in groups exposed to anoxia and meconium (Groups IV and V).
Conclusions:
- A brief episode of anoxia prior to meconium aspiration can increase lung sensitivity to injury.
- Hypoxia appears to exacerbate meconium-induced lung injury, with TNFalpha playing a potential moderating role in the pulmonary inflammatory response.
