| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* 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
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-
) has
been shown to upregulate VEGF during tissue hypoxia, we hypothesized
that HIF1- 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- 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- 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.
This article has been cited by other articles:
|
|
 |
|
  D. I. Loube Technologic Advances in the Treatment of Obstructive Sleep Apnea Syndrome Chest, November 1, 1999; 116(5): 1426 - 1433. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
