Society of University SurgeonsMatrix metalloproteinase inhibition limits arterial enlargement in a rodent arteriovenous fistula model☆,☆☆
Section snippets
Material and methods
Adult male Sprague-Dawley rats (weight 350 to 450 g) were used for this experiment. Clean surgical technique was used for all procedures. Anesthetic (50 mg/kg sodium pentobarbital; Abbott Laboratories, Chicago, Ill.) was administered through intraperitoneal injection. Fistula construction was performed after intravenous injection of 100 units/kg beef lung heparin (The Upjohn Co, Kalamazoo, Mich.). Animals recovered from the operation in separate cages with free access to food and water. All
Results
All results are expressed as means ± SD. Three rats died during the initial surgical procedure, 3 were killed after unsuccessful AVF creation, 4 did not survive measurement of the aorta and iliac arteries, and 4 AVFs were found to be occluded during the final surgical procedure. Thus 48 rats were available for comparison at the final surgical procedure, including 10 in the sham, 10 in the control, 14 in the vehicle, and 14 in the treatment groups.
Discussion
Administration of RS-113,456 to rats with increased left CFA blood flow caused by an AVF prevented abdominal aortic enlargement compared with control AVF rats or AVF rats treated with vehicle alone. Treatment with RS-113,456 did not completely inhibit aortic enlargement; the average aortic diameter in the treatment group was significantly larger than in rats who did not have an AVF (sham group).
To our knowledge, prevention of flow-mediated arterial enlargement has not been attempted with other
Acknowledgements
We thank Byron Brown, PhD, for reviewing the statistical analyses, Michelle Bendeck, PhD, for assistance with references and manuscript preparation, and Sarika C. Joshi and Joshua M. Hull for their technical assistance in animal husbandry and performance of procedures as described. Material support was provided by the Inflammatory Diseases Section, Roche Bioscience, Palo Alto, Calif.
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Cited by (0)
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Supported in part by the American Heart Association, California affiliate grant 95-255, the Office of Technology and Licensing, Stanford University, and the Lifeline Foundation 1997 Student Fellowship Award.
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Reprint requests: Ronald L. Dalman, MD, Surgical Service, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA 94304.