The Journal of Thoracic and Cardiovascular Surgery, Vol 104, 1582-1588, Copyright © 1992 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
The effect of transforming growth factor-alpha on airway angiogenesis
DE Schraufnagel, DA Arzouman, M Sekosan and YK Ho
Department of Medicine, University of Illinois, Chicago 60680-6998.
A problem in lung transplantation is tracheal or bronchial dehiscence from
ischemia. To determine if an angiogenic factor applied to the airway would
improve capillary regrowth, a three-ring segment of trachea was completely
severed and sutured in rats. In one group of animals the ischemic segment
was wrapped with Gelfoam soaked in an angiogenic factor, transforming
growth factor-alpha. In a second group the ischemic area was wrapped with
Gelfoam soaked with only the vehicle. In a third group the devascularized
area received no additional treatment. One animal from each group was
killed daily for 7 days after operation. The tracheal vasculature was cast
and viewed by light and scanning electron microscopy. None of the four
animals that died early were in the transforming growth factor-alpha group.
All animals lost weight between the day of operation and death, but this
was least in the transforming growth factor-alpha group (p = 0.05). The
light microscopy showed ischemic changes and the development of granulation
tissue. The scanning electron microscopy of the vascular casts showed
extensive loss of the vessels in the cut area. On day 1 the vessels of all
animals dilated and their walls became rough. By day 3 a few corkscrew
vessels penetrated the ischemic zone. By day 4 the animal that received
transforming growth factor-alpha had more capillaries than the others. By
day 6 revascularization in the transforming growth factor-alpha animal was
abundant. Besides budding, new capillaries appeared to develop by lateral
growth. After the fifth day vessels about 30 to 50 microns in diameter
bulged focally. On the bulges, ridges the size, shape, and pattern of
capillaries formed. Capillary formation in this manner has not been
reported previously. Revascularization emerged sooner and more extensively
with transforming growth factor-alpha. No adverse effect of transforming
growth factor- alpha was found.