PREVENTIVE EFFECT OF LONG ACTING Β2-AGONISTS ON STATIN INDUCED MYOPATHIES

Objective: To identify the histological effectsof statin-induced skeletal muscle myopathy in a Rat model and tofind protective effect of long acting β2-agonists.Study Design: Laboratory based experimental randomized controlled trial.Place and Duration of Study: Study was conducted at the department of Anatomy, Army Medical CollegeRawalpindi in collaboration with National Institute of Health (NIH) Islamabad and Armed forces institute ofPathology (AFIP) Rawalpindi, from Jan 2015 to Jun 2016.Material and Methods: Adult male Sprague-Dawley rats were procured from NIH Islamabad. Their averageapproximate age was 70-80 days and weight range was 250 ± 50 grams. The animals were randomly selected anddivided into three groups. Group A was the control. Each rat of group B received Simvastatin dissolved indistilled water, by oral gavage (60mg/kg/day) once daily, for 12 weeks. Animals of group C received simvastatindissolved in distilled water, (60mg/kg/day) once daily plus formoterol dissolved in distilled water (3μg/kg/day)once daily for 12 weeks. Both were administered with the help of oral gavage. The animals were sacrificed afterthree months of the experimental period. Extensor digitorum longus (EDL) tendon was isolated and dissectedout. Tissue processing was done on the EDL muscle followed by Haematoxylin and Eosin staining. Fiber crosssectionalareas, Number of myofibers and Central Myonuclei were counted per high power field in eachspecimen of all three groups.Results: Examination of H&E stained sections of the extensor digitorum longus muscle of the control grouprevealed the histological structure of skeletal muscle. Cross sectional area of myofibers and number of myofiberswere significantly lower in group B as compared to the control group A. Group C showed significant increase incross sectional area of myofibers and number of myofibers as compared to group B. No central myonuclei wasseen in any section.Conclusion: Simvastatin induced the histomorphological changes in the skeletal muscle of experimental rats byreducing myofiber size and number. Formoterol co-administration minimized simvastatin induced myopathy bysignificantly increasing myofiber size and number.