Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels.

STUDY DESIGN: The effects on nerve tissue and blood vessels of locally applied chondroitinase ABC were studied in two experimental models using chymopapain and the vehicle of chondroitinase ABC for controls. OBJECTIVES: To assess the effects of chondroitinase ABC on blood vessels and nerve tissue after local application. SUMMARY OF BACKGROUND DATA: Chondroitinase ABC has been suggested for chemonucleolysis because it has a high specificity for nucleus pulposus matrix, which could mean a high efficiency in dissolving disc tissue combined with a low risk of side effects on other tissues. METHODS: Chondroitinase ABC or controls were injected intrathecally in the pig, and nerve conduction velocity and histologic changes were assessed after 7 days. The same substances were injected into the hamster cheek pouch and studied for 60 minutes for microvascular effects. The vehicle for the enzyme was used as a negative control and chymopapain in a therapeutic concentration served as a positive control. RESULTS: In all series there was a slight intrathecal fibrotic reaction that was most pronounced after chymopapain injection. The effects on nerve conduction velocity and nerve morphology were similar between chondroitinase ABC and its vehicle. Chymopapain induced a significant reduction in nerve conduction velocity and pronounced histologic changes. In the cheek pouch, chymopapain induced a stand-still of blood flow at the injection site, and microhemorrhage and macromolecular leakage from the vessels at the border of the injection site. Only a slightly reduced blood flow was occasionally found after injection of chondroitinase ABC and controls. CONCLUSIONS: In agreement with the current literature, these observations indicate that chondroitinase ABC is safe regarding adverse effects on nerve tissue and blood vessels. The slight reduction in conduction velocity after intrathecal injection of chondroitinase ABC or its vehicle is most likely the result of surgical injury while releasing the nerve roots from the intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy per se, and probably have no pathophysiologic significance.

The effect of chondroitinase ABC on rabbit intervertebral disc. Radiological, histological and electron microscopic findings.

Seventy-eight rabbit lumbar discs were evaluated by radiographs and histology after the injection of chondroitinase ABC (40 U/ml for each disc) and compared with injection with phosphate buffer, and also with a control group who were not injected. There was considerable narrowing of the disc space after chondroitinase ABC injection. Safranin-0 depletion was present in the anterior part of the annulus fibrosus near to the nucleus pulposus in all the treated discs, indicating loss of proteoglycan. Electron microscopy showed collapse of the chondrocytes and notochordal cells. These findings suggest that chondroitinase ABC may be another chemonucleolytic agent which decreases disc volume and consequently decompresses the spinal cord or nerve roots; its effects were confined to the tissues within the intervertebral disc.

Comparison of lesions induced by intra-articular injections of quinolones and compounds damaging cartilage components in rat femoral condyles.

Twenty-five microliters of a 2% saline solution of levofloxacin (LVFX) or ciprofloxacin (CPFX) was injected every other day for 2 wk into the knee joint space of CD rats (weighing 62.7-86.7 g) from the age of 3 wk. Early in the course of injection, histologic examination revealed chondrocyte necrosis without marked matrix change in the articular cartilage of the femoral condyles adjacent to the intercondylar groove. After 7 injections, the surface and intermediate zones of the articular cartilage showed extensive necrosis, sometimes with cavity formation in the center of the same portion. Papain completely depleted matrix basophilia in all zones throughout the condyle and caused cartilage necrosis with cavity formation. One injection of iodoacetic acid caused necrosis of almost all chondrocytes over the entire condyle, but chondrocytes sometimes remained alive in the portion where cavity formation was induced by quinolones. Chondroitinase depleted the matrix basophilia, and sometimes produced necrotic areas. DNA synthesis inhibitors n-ethylmaleimide, CPT-11, and etoposide (VP-16) caused chondrocyte necrosis, but never caused cavities in the articular cartilage. The DNA synthesis inhibitors n-ethylmaleimide, CPT-11, and hydroxyurea were administered concurrently with po LVFX administration and significantly increased the incidence of LVFX-induced cavity formation. n-Ethylmaleimide was the most effective of all the inhibitors. The quinolone-induced cavity formation is suggested to be site specific in the articular cartilage of rat femoral condyles. The depletion of matrix proteoglycans and chondrocyte necrosis may be necessary, although insufficient, to produce such lesions. Disruption of the collagen framework is suspected to contribute to their development. Involvement of altered DNA metabolism may play a role in the chondrocyte necrosis that occurs early in the specific sites.