Giorgio C. La Scala, MD, David A. O'Donovan, MD, Ivan Yeung, PhD, Iona Leong, BDS, MSc, Maria Mendes, BSc, MLT, Patrick D. Addison, MBChB, Kenneth P. H. Pritzker, MD, Cho Y. Pang, PhD, Peter C. Neligan, MD, and Christopher R. Forrest, MD, MSc.
Introduction: We have previously demonstrated
significant (p<0.05) attenuation of radiation-induced craniofacial
bone growth inhibition pre-treating with the known cytoprotective agent
Amifostine, using the infant rabbit OZC model. To understand the mechanism of
this effect, experiments were designed to determine the effects of single
fraction orthovoltage radiation on regional blood flow to the infant rabbit OZC
with and without cytoprotection.
Methods: Seven-week old New Zealand male infant
rabbits randomized in 4 groups received single dose orthovoltage radiation to
the right OZC using protocols established by us previously: 0Gy (C),
35Gy (S35), 0Gy or 35Gy 20 min. after pre-treatment with Amifostine 300
mg/kg IV (respectively CA and S35A). Blood flow to both OZC, soft
tissue and hemi-mandibles was measured 1, 14 and 63 days after radiation using
the modified 15µm radioactive microsphere technique (n=6/group).
Histological specimens were harvested for blood vessel counts using Safranin-O
stains at day 1 and 100 post-radiation (n=10/group).
Results: Blood flow to the irradiated OZC was significantly (p<0.05)
greater 1 day following single dose orthovoltage radiation compared to
non-radiated controls. This increase was not observed in the Amifostine pre-treated
animals and 14 and 63 days post-radiation.
Rt OZC blood flow (ml/100g/min)
|
|
1 day
|
14 days
|
63 days
|
|
C
|
5.17±0.78a
|
8.57±1.42a
|
7.92±0.79a
|
|
CA
|
6.40±1.75a
|
7.57±2.83a
|
11.94±1.77a
|
|
S35
|
20.4±2.74b
|
5.21±0.63a
|
6.12±1.23a
|
|
S35A
|
13.32±1.3ab
|
8.43±2.01a
|
8.86±1.35a
|
(Mean±SEM, groups not sharing same letter are different p<0.05)
Histological blood vessel counts in the OZC were significantly decreased
in the S35 group at 100 days post-radiation.
Conclusions: Single dose orthovoltage radiation produces a
temporary elevation in regional blood flow to the OZC that returns to control
levels within 14 days. Pre-treatment with the cytoprotective agent, Amifostine,
was found to attenuate this response. The significance of these findings as
they pertain to the mechanism of radiation-induced craniofacial bone growth
inhibition will be discussed.
