SKELETAL-MUSCLE EDEMA AND MUSCLE-FIBER NECROSIS DURING SEPTIC SHOCK -OBSERVATIONS WITH A PORCINE SEPTIC SHOCK MODEL

In domestic pigs, intermitted application of Escherichia coli-endotoxi n was used to create an animal model for a prolonged hypo- and hyperdy namic septic shock-like state and to investigate mechanisms of multipl e organ failure. Here, we describe the changes in skeletal muscle afte r 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions ins tead of endotoxin served as controls. The earliest lesions were endoth eli al cell damage with endomysial oedema and swelling of mitochondria in muscle fibres. With increasing degree of endothelial cell damage, pericytes showed degenerative changes with cytoplasmic fragmentation a nd karyolysis. After 48 h of shock, endomysial oedema was increased wi th fibrinogen present. Muscle fibre diameters were increased and swoll en mitochondria and segmental necrosis of muscle fibres were frequentl y observed. However, phagocytic reaction or regenerative changes were not detected. In this respect, skeletal muscle lesions in septic shock differ from ischemic damage, which is characterized by early phagocyt osis. Tumour necrosis factor alpha (TNF alpha) was increased greatly a nd significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle f ibres by the endotoxin and/or the increased levels of TNF alpha and in direct damage because of the increased diffusion distance, due to the endomysial oedema. The loss of blood proteins into the endomysium may also play a role in generating hypoproteinemia in patients with septic shock.