Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury

Abstract

Introduction: Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Methods: Sheep were randomized to a sham-injured control group (n=6) or ALI/Sepsis group (n=7). The sheep in the ALI/Sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 hours. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. Results: The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (p<0.015 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (p<0.05 each). Conclusions: This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.

Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia

“…The surgical protocol has been described in previous studies. 1718 Briefly, under isoflurane anaesthesia (Aestiva/5, Compact 7100, Tec 7 vaporizer, Datex Ohmeda, Madison, Wisconsin, USA) administered via endotracheal tube, the right femoral artery was cannulated for arterial access (Intracath, 16GA, 24IN, Becton Dickinson, Sandy, Utah, USA) and a thermodilution catheter (Swan Ganz, model 131F7, Baxter, Edwards Division, Irvine, California, USA) was introduced through the right common jugular vein into the pulmonary artery. A catheter (Duralastic Silicone Tubing DT08, 0.062 in.…”

“…The pulmonary transvascular fluid flux was evaluated every 3 h based on the lung lymph flow measurements. 1718 Systemic vascular resistance index (SVRI) was calculated using standard equations. Urine output was measured every 3 h.…”

Vascular Endothelial Growth Factor in Acute Lung Injury and Acute Respiratory Distress Syndrome

“…Increased VEGF and VEGFR2 expression in the lung has also been reported in an animal model of sea water immersion after open chest trauma-induced ALI [120,121,122]. …”

“…Using an ovine smoke inhalation and pneumonia model of lung injury, Lange et al [120] attempted to evaluate the time course of changes in VEGF expression. Linear increases in transvascular fluid flux and lung water content were observed following induction of lung injury.…”

Multiple versus single injections of fluorescent microspheres for the determination of regional organ blood flow in septic sheep

“…13 In our established ovine model of sepsis, we utilized the fluorescent microsphere technique to assess the pathophysiological alterations during sepsis and to test the effects of new treatment strategies on regional blood flow to different organs. 9,14,15 We considered the multiple injection technique to be the method of choice because it allows testing organ blood flow at various time points in the same animals. However, the effects of multiple versus single injections of microspheres on regional blood flow in our model have not yet been compared.…”