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The Effects of Toradol on Postoperative Intimal Hyperplasia in a Rat Carotid Endarterectomy Model: Laboratory Research

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Leighton Satterfield

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Aliza T. Brown

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Hongjiang Chen, MD

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Nuran Ercal

University of Missouri-Rolla Rolla, Missouri

Tulin O. Price

University of Missouri-Rolla Rolla, Missouri

Jie Gao

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Khalil Ibrahim

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas

Mohammed M. Moursi, MD

University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas, moursimohammedm{at}uams.edu

Carotid endarterectomy (CEA) and more recently carotid artery stenting are the treatments of choice for atherosclerotic disease of the extracranial carotid arteries; however, early restenosis caused by neointimal hyperplasia confounds surgical therapy. Oxidative stress has been implicated in the progression of intimal hyperplasia. The authors hypothesized that ketorolac tromethamine (Toradol), a nonsteroidal antiinflammatory drug that is a potent cyclooxygenase inhibitor, would decrease oxidative stress and thereby reduce intimal hyperplasia in a rat CEA model. Twenty-nine male Sprague-Dawley rats underwent CEA and were divided into 3 treatment groups as follows: (1) control (placebo), (2) 7.5 mg/kg Toradol, and (3) 10 mg/kg Toradol. Toradol treatment began 2 days before CEA and continued for 2 weeks. Two weeks after endarterectomy, carotid arteries were fixed, harvested, and examined for platelet activity (platelet reactive units), oxidative stress (malondialdehyde and glutathione), and intimal hyperplasia (measured as percentage of luminal stenosis). Platelet activity, malondialdehyde and glutathione, and intimal hyperplasia were all significantly lowered in both 7.5- and 10-mg/kg doses of Toradol versus control. Toradol given daily beginning 2 days before CEA and ending 2 weeks after the procedure was effective at significantly reducing platelet activity, oxidative stress, and intimal hyperplasia development in the rat without any increase in bleeding. Although the mechanism of action of this reduction is not completely understood, one possible explanation may be through the inhibition of reactive oxygen species production.

Key Words: intimal hyperplasia • rat • carotid endarterectomy • Toradol • oxidative stress

Vascular and Endovascular Surgery, Vol. 41, No. 5, 402-408 (2007)
DOI: 10.1177/1538574407304506


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