Effect of prostaglandin E2 injection on the structural properties of the rat patellar tendon.

BACKGROUND: Increased tendon production of the inflammatory mediator prostaglandin E2 (PGE2) has been suggested to be a potential etiologic agent in the development of tendinopathy. Repeated injection of PGE2 into tendon has been proposed as a potential animal model for studying treatments for tendinopathy. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit PGE2 production and are commonly prescribed in treating tendinopathy have been shown to impair the healing of tendon after acute injury in animal models. The contradictory literature suggests the need to better define the functional effects of PGE2 on tendon. Our objective was to characterize the effects of PGE2 injection on the biomechanical and biochemical properties of tendon and the activity of the animals. Our hypothesis was that weekly PGE2 injection to the rat patellar tendon would lead to inferior biomechanical properties. METHODS: Forty rats were divided equally into four groups. Three groups were followed for 4 weeks with the following peritendinous injection procedures: No injection (control), 4 weekly injections of saline (saline), 4 weekly injections of 800 ng PGE2 (PGE2-4 wks). The fourth group received 4 weekly injections of 800 ng PGE2 initially and was followed for a total of 8 weeks. All animals were injected bilaterally. The main outcome measurements included: the structural and material properties of the patellar tendon under tensile loading to failure, tendon collagen content, and weekly animal activity scores. RESULTS: The ultimate load of PGE2-4 wks tendons at 4 weeks was significantly greater than control or saline group tendons. The stiffness and elastic modulus of the PGE2 injected tendons at 8 weeks was significantly greater than the control or saline tendons. No differences in animal activity, collagen content, or mean fibril diameter were observed between groups. CONCLUSIONS: Four weekly peritendinous injections of PGE2 to the rat patellar tendon were not found to be an effective model of clinical tendinopathy. In contrast, improved structural and material properties of the patellar tendon were found after PGE2 injection. While PGE2 has been thought to have a contributory role in the development of tendinopathy and anti-inflammatory medications remain a common treatment, our results suggest a positive role of PGE2 in tendon remodeling in some circumstances.

The effects of common anti-inflammatory drugs on the healing rat patellar tendon.

BACKGROUND: Tendon injuries that occur at the osteotendinous junction are commonly seen in clinical practice and range from acute strain to rupture. Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of these conditions, but the effect that these agents may have on the healing response at the bone-tendon junction is unclear. HYPOTHESIS: In response to an acute injury at the osteotendinous junction, the healing patellar tendon will have inferior biomechanical properties with administration of anti-inflammatory drugs as compared with acetaminophen and control. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 215 Sprague-Dawley rats underwent transection of the patellar tendon at the inferior pole of the patella, which was subsequently stabilized with a cerclage suture. The animals were then randomized into 7 groups and administered 1 of the following analgesics for 14 days: ibuprofen, acetaminophen, naproxen, piroxicam, celecoxib, valdecoxib, or control. At 14 days, all animals were sacrificed, and the extensor mechanism was isolated and loaded to failure. Biochemical analysis of the repair site tissue was performed. Animal activity throughout the study was monitored using a photoelectric sensor system. RESULTS: The control group demonstrated greater maximum load compared with the celecoxib, valdecoxib, and piroxicam groups (P < .05). The acetaminophen and ibuprofen groups were also significantly stronger than the celecoxib group (P < .05) but not statistically different than the control group. A total of 23 specimens had failure of the cerclage suture with the following distribution: control (0/23), ibuprofen (0/23), acetaminophen (0/24), naproxen (3/24), piroxicam (4/24), celecoxib (6/22), and valdecoxib (10/24). The difference in distribution of the failures was significant (P < .001). CONCLUSIONS: Anti-inflammatory drugs, with the exception of ibuprofen, had a detrimental effect on healing strength at the bone-tendon junction as demonstrated by decreased failure loads and increased failures of the cerclage suture. Acetaminophen had no effect on healing strength. The biomechanical properties paralleled closely with the total collagen content at the injury site, suggesting that these agents may alter healing strength by decreasing collagen content. CLINICAL RELEVANCE: Selective and nonselective cyclooxygenase (COX) inhibitors should be used judiciously in the acute period after injury or surgical repair at the bone-tendon junction.

Suture plication, thermal shrinkage, and sclerosing agents: effects on rat patellar tendon length and biomechanical strength.

BACKGROUND: Shortening or tightening of dense, collagenous tissues is often desirable in the treatment of laxity. PURPOSE: To compare the effect of stress-protection suture, radiofrequency thermal shrinkage combined with stress-protection suture, and a 5% sodium morrhuate sclerosing injection on the length and biomechanical strength of the rat patellar tendon. HYPOTHESIS: Sclerosing agents will increase tendon mechanical strength. Thermal shrinkage combined with stress-protection suture and stress-protection suture only will cause a short-term decrease in tendon strength. All 3 methods will produce equivalent shortening of the tendon. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-six female retired breeder rats were split into 4 groups, each receiving 1 of the 3 aforementioned treatments plus a control group that received a saline injection. After 4 weeks' survival, the length and biomechanical properties of the patellar tendons were measured and compared to the contralateral untreated tendon. RESULTS: Rats treated with stress-protection suture had shorter tendons. Radiofrequency thermal shrinkage combined with stress-protection suture yielded tendons that were both shorter and stronger than were the untreated contralateral tendons. The sodium morrhuate-injected tendons were stronger whereas the saline-treated tendons were weaker than were their respective untreated contralateral tendons. CONCLUSION: Surgical stress-protection suture without radiofrequency shrinkage is most effective at shortening the length of the rat patellar tendon, whereas radiofrequency thermal shrinkage combined with stress-protection suture as well as sodium morrhuate are effective at increasing the strength of rat patellar tendons. CLINICAL RELEVANCE: Judicious use of thermal shrinkage in combination with stress protection may improve ligament strength and decrease laxity.

The effect of analgesic agents on the healing rat medial collateral ligament.

BACKGROUND: Studies have suggested that some nonselective nonsteroidal anti-inflammatory drugs, including piroxicam, may improve ligament healing, whereas other nonsteroidal anti-inflammatory drugs, including ibuprofen and the cyclooxygenase-2 inhibitor celecoxib, may have no effect on the mechanical properties or may even deter the healing process. These results might reflect variations in cyclooxygenase enzyme selectivity by different drugs or, alternatively, may be related to their analgesic properties because it is generally accepted that early activity improves ligament healing. HYPOTHESIS: Nonselective nonsteroidal anti-inflammatory drugs improve ligament healing, whereas other analgesics provide lesser degrees of improvement, and cyclooxygenase-2 inhibitors are detrimental. STUDY DESIGN: Controlled laboratory study. METHODS: One hundred fifty-five Sprague-Dawley rats were divided into 7 treatment groups (piroxicam, naproxen, rofecoxib, butorphanol, 2 doses of acetaminophen, and control). The right medial collateral ligament of each rat was transected, and the drugs were administered postoperatively on days 1 to 6. On day 14, the rats were sacrificed, and mechanical testing was performed on the medial collateral ligament. RESULTS: The piroxicam group demonstrated significantly greater load to failure (27%) compared with the control. No significant differences were observed between other groups. CONCLUSIONS: Piroxicam improves ligament healing, but this effect cannot be attributed to all nonselective nonsteroidal anti-inflammatory drugs. Opiate analgesics, acetaminophen, and cyclooxygenase-2 inhibitors do not appear to categorically affect ligament healing. CLINICAL RELEVANCE: In the treatment of ligament injury, piroxicam may be a drug of choice.