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J Thorac Cardiovasc Surg 2000;120:916-922
© 2000 The American Association for Thoracic Surgery
General Thoracic Surgery |
From the Thoracic and Cardiovascular Surgery Research Laboratory, University of Virginia Health Sciences Center, Charlottesville, Va.
This research is supported by National Institutes of Health grants RO1 HL48242 and T32 HL07849 and by NICHD/NIH through cooperative agreement U54 HD28934.
Received for publication May 4, 2000. Revisions requested July 10, 2000; revisions received July 20, 2000. Accepted for publication July 27, 2000. Address for reprints: Irving L. Kron, MD, Department of Thoracic and Cardiovascular Surgery, University of Virginia Health Sciences Center, PO Box 801359, MR4, Room 3111, Charlottesville, VA 22908-1359 (E-mail: ikron{at}virginia.edu).
Abstract
Objective: Epidermal growth factor has been shown to play an important role in prenatal and postnatal lung development, but little is known about its effects on adult lung growth. We hypothesized that postpneumonectomy compensatory lung growth can be augmented by the administration of epidermal growth factor.
Methods: Adult Sprague-Dawley rats were divided into 3 groups. Sham left thoracotomy was performed in the first group (group C), left pneumonectomy in the second group (group P), and left pneumonectomy with administration of epidermal growth factor (0.2 µg/g body weight intraperitoneally, at 72-hour intervals) in the third group (group E). The right lung growth was studied in each group 1, 3, 5, 10, and 21 days after the operation. Lung weights (in grams) and volumes (in milliliters) were expressed as a ratio to the total body weight (in kilograms) (lung weight and volume indices). Epidermal growth factor receptor was quantitated by using Western blotting.
Results: Using analysis of variance and contrast analysis, we noted a significant increase in lung weight index in group E versus group P rats at 3 days (3.08 vs 2.75; P = .034) and 21 days (4.62 vs 3.61; P = .006). Lung volume index was significantly increased in group E versus group P rats at 5 (16.98 vs 15.09), 10 (24.48 vs 18.81), and 21 (28.54 vs 21.01) days (P < .001). Epidermal growth factor receptor was noted to be up-regulated in the lungs of animals that received exogenous epidermal growth factor.
Conclusions: This study demonstrates that administration of exogenous epidermal growth factor has a significant effect on postpneumonectomy lung growth. This process may be mediated by an up-regulation of growth factor receptor expression in the contralateral lung.
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