DOXORUBICIN CHEMOMYECTOMY IS ENHANCED WHEN PERFORMED 2 DAYS FOLLOWINGBUPIVACAINE INJECTIONS - THE EFFECT COINCIDES WITH THE PEAK OF MUSCLESATELLITE CELL-DIVISION

PURPOSE. Doxorubicin is effective in permanently removing muscle after direct injection into the eyelid for treatment of blepharospasm and h emifacial spasm. However, patients often require two or more injection series before full abatement of their spasms is achieved. Local anest hetics cause muscle necrosis, followed by regeneration, a process that requires activation and division of muscle satellite cells. This stud y examined whether the muscle toxicity of doxorubicin could be amplifi ed by injection of doxorubicin into the eyelid of rabbits 2 days after a local anesthetic injury, perhaps exploiting the toxic effects of do xorubicin on satellite cells at the peak time of their division after injury. METHODS. Rabbit eyelids received two series of injections of b upivacaine and hyaluronidase spaced 18 hours apart. Two days later, th e eyelids were injected with either 0.5 or 1 mg doxorubicin. Animals w ere monitored daily for onset and duration of skin injury. After 1 mon th, the eyelids were assessed for muscle loss using histologic and mor phometric techniques. RESULTS. Injection of doxorubicin during the pea k of satellite cell activation and division 2 days after injury signif icantly increased muscle loss over doxorubicin alone. This treatment d id not result in increased skin injury compared with doxorubicin alone . CONCLUSIONS. Permanent muscle loss was increased when doxorubicin wa s injected at the peak of satellite cell division 2 days after injury of the muscle with bupivacaine in rabbit eyelid, taking advantage of t he antimitotic effects of doxorubicin on satellite cell division durin g the period of active regeneration. When local anesthetic injection i mmediately preceded the doxorubicin injection, increased myotoxicity w as not seen. The injection of doxorubicin into muscle 2 days after a p revious injury maximizes muscle loss. The increased muscle loss provid ed by this double treatment may decrease the number of injection visit s required by blepharospasm and hemifacial spasm patients during their course of treatment, thus reducing the number of patients with side e ffects, which increases with repeated exposures of the eyelid to doxor ubicin.