The effects of Toradol on postoperative intimal hyperplasia in a rat carotid endarterectomy model: laboratory research.
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.
Kalapatapu
Venkat R
VR
University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System Little Rock, Arkansas 72205, USA.
Satterfield
Leighton
L
Brown
Aliza T
AT
Hongjiang Chen
Ercal
Nuran
N
Price
Tulin O
TO
Jie Gao
Ibrahim
Khalil
K
Moursi
Mohammed M
MM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D006965:Hyperplasia; D020911:Ketorolac Tromethamine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D020911:Ketorolac Tromethamine; D008315:Malondialdehyde; D005978:Glutathione