Articles |

Differential Regulation of Vascular Endothelial Growth Factor During Ventilated Pulmonary Ischemia* FREE TO VIEW

Aimee Yu, MD; A. Alcasabas; G. Semenza, MD; P. Becker, MD
Author and Funding Information

*From the Johns Hopkins School of Medicine, Baltimore, MD.

Correspondence to: Aimee Yu, MD, Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224

Chest. 1999;116(suppl_1):32S. doi:10.1378/chest.116.suppl_1.32S
Text Size: A A A
Published online

Pulmonary vascular permeability increases during ventilated ischemia, before reperfusion, in isolated ferret lungs. The mechanism of this injury is not well understood, but it is likely to differ from other organs, as pulmonary ischemia is not necessarily synonymous with hypoxia if ventilation is maintained when blood flow is impaired.

Preliminary evidence from our laboratory demonstrates that vascular endothelial growth factor (VEGF), a potent mediator of increased vascular permeability, is upregulated during pulmonary ischemia. Interestingly, this VEGF induction is not oxygen dependent and occurs to the same degree in lungs ventilated with oxygen or nitrogen during 180 min of ischemia.

We speculated that VEGF might be induced by more than one mechanism during ischemia, depending on whether oxygen was present. Because the transcription factor hypoxic inducible factor 1-alpha (HIF1-α) has been shown to upregulate VEGF during tissue hypoxia, we hypothesized that HIF1-α would increase during pulmonary ischemia with hypoxic ventilation, but not necessarily during ischemia with oxygen ventilation.

To test this hypothesis, separate groups of isolated ferret lungs were flushed of residual blood with physiologic salt solution containing no glucose, and they were subjected to 45 or 180 min of ventilated ischemia (37°C). Lungs in each group were ventilated with either 0% O2-5% CO2 or 95% O2-5% CO2. After ischemia, freeze clamp biopsy specimens were taken from the right lung for measurement of HIF1-α and VEGF expression, then the right hilum was clamped, and vascular permeability was assessed by measurement of osmotic reflection coefficient for albumin in the left lung. Results were compared with control lungs flushed with glucose-containing physiologic salt solution, and they were ventilated with a normoxic gas mixture for a minimal ischemia period.

Preliminary results suggest upregulation of HIF1-α protein, measured by Western blot analysis of tissue homogenates, in lungs exposed to 180 min of anoxic, but not hyperoxic, ischemia. VEGF messenger RNA increased approximately fourfold after 180 min of ischemia regardless of oxygen tension in the ventilatory gas. This increase in VEGF was associated with approximately a 75% decrease in osmotic reflection coefficient for albumin in the same lungs, and that was also oxygen independent.

These results suggest that VEGF may be differentially regulated during ventilated pulmonary ischemia. Further experiments will confirm this finding, and we will continue to explore mechanisms regulating VEGF expression and the role of VEGF in the generation of pulmonary ischemic injury.




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543