Effect of ketorolac tromethamine (Toradol) on ischemia-reperfusion injury in skeletal muscle.
The eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2), contribute to neutrophil adhesion and arteriole vasoconstriction, important microcirculatory events in ischemia-reperfusion (I-R) injury. The purpose of this study was to evaluate the effect of ketorolac on I-R injury of skeletal muscle. A videomicroscopic preparation of gracilis muscle in male Wistar rats (n=7) in two experimental groups was evaluated: Group 1-4 hr global ischemia only (19 arterioles, 19 venules), and Group 2-4 hr ischemia plus ketorolac (13 arterioles, 14 venules). Ketorolac (0.86 mg/kg, i.m.) was given 30 min prior to reperfusion. The number of neutrophils, rolling and adherent, was counted in 100-micron venular segments, and arteriole diameters were measured at 5, 15, 30, 60 and 120 min of reperfusion. The I-R-induced increase in neutrophil adhesion was significantly reduced by ketorolac, which significantly increased arteriolar vasodilation in the first 30 min of reperfusion and significantly reduced the I-R-induced vasoconstriction in arterioles at 30 min; this effect was lost at 1 hr of reperfusion. Although ketorolac augments immediate arteriole vasodilation and blocks subsequent vasoconstriction, this effect appears to be transient. These findings suggest that ketorolac may have potential as a treatment for I-R injury.
Yao
K A
KA
Division of Plastic Surgery, University of Nevada School of Medicine, Las Vegas 89102, USA.
Roth
A C
AC
Stephenson
L L
LL
Suchy
H
H
Zamboni
W A
WA
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D020911:Ketorolac Tromethamine; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009504:Neutrophils / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014325:Tromethamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D014046:Tolmetin