EXPERIMENTAL LOVASTATIN MYOPATHY

Lovastatin (LS) is a potent HMG-CoA inhibitor used in the treatment of hypercholesterolemia. In humans it can cause a severe, necrotizing my opathy with myoglobinuria and renal failure. To investigate the pathog enesis of LS-induced myopathy we studied the effects of LS on rat skel etal muscle. Lewis rats were gavage-fed 1 mg/g body weight/day of LS. Control rats received carboxymethylcellulose-based suspension by gavag e. Gastrocnemius and soleus, fast and slow twitch muscles respectively , were studied by light and electron microscopy. By day 10 LS-treated rats became severely weak. Gastrocnemius was severely affected with de generation of membranous organelles and microvacuole formation, but so leus was spared. Eventually, 20-50% of the gastrocnemius but none of t he soleus fibers became necrotic. Non-necrotic fibers showed no increa ses of acid phosphatase, indicating that autophagy was not excited. We conclude that LS causes muscle injury by inducing degeneration of mem branous organelles, and fast twitch muscle fibers are selectively vuln erable to LS myopathy.