Muscle necrosis and regeneration after envenomation by Bothrops jararacussu snake venom

The lesions caused by sublethal doses of Bothrops jararacussu venom injected into tibialis anterior (tib. ant.) muscles of mice were studied with paraffin sections. Doses of 5 and 20 micrograms produced a large area of necrosis in tib. ant., but hardly affected neighbouring muscles. Phagocytosis of necrotic remnants was followed by marked regeneration of the muscle fibres. Within two weeks of the 5 micrograms dose there was recovery to near normal appearance and slight fibrosis. With 20 micrograms, a circumscribed scar and stronger interstitial fibrosis developed in the tib. ant. Most regenerated muscle fibres were small, but varied in diameter, retained central nuclei for three months (the longest survival) and were surrounded by collagen. Doses of 80 and 200 micrograms produced widespread coagulative necrosis of tib. ant., though neighbouring leg muscles were relatively spared. Myonecrosis was evident microscopically at 10 min, and over the next week the necrotic muscle remained acellular and devoid of inflammatory reaction except at the very edge. Blood vessels within and outside tib. ant. often became hyalinized and thrombosed. Phagocytosis of debris proceeded from the periphery, and after two weeks the muscle was replaced by fibro-adipose tissue. There was little if any muscle fibre regeneration. Abscesses developed in the vicinity of the injection site in several mice receiving high venom doses, but never after low doses or saline. Muscle necrosis after B. jararacussu venom seems due primarily to direct action of the venom, though vascular thrombosis and ischaemia may contribute. The venom can cause fibrosis of muscle and hinder or prevent muscle fibre regeneration.