Sunday, November 3, 2002
289

Hemodynamic and Histopathologic Investigation of the Mechanism of Radiation-Induced Craniofacial Bone Growth Inhibition With and Without Cytoprotection in the Infant New Zealand Rabbit Orbito-Zygomatic Complex (Ozc)

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.


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