Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model

Abstract

In domestic pigs, intermitted application of Escherichia coli-endotoxin was used to create an animal model for a prolonged hypo- and hyperdynamic septic shock-like state and to investigate mechanisms of multiple organ failure. Here, we describe the changes in skeletal muscle after 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions instead of endotoxin served as controls. The earliest lesions were endothelial 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 and karyolysis. After 48 h of shock, endomysial oedema was increased with fibrinogen present. Muscle fibre diameters were increased and swollen mitochondria and segmental necrosis of muscle fibres were frequently 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 phagocytosis. Tumour necrosis factor alpha (TNF alpha) was increased greatly and significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle fibres by the endotoxin and/or the increased levels of TNF alpha and indirect 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.

Sepsis stimulates release of myofilaments in skeletal muscle by a calcium‐dependent mechanism

“…Sepsis‐induced changes in skeletal muscle morphology were reported previously in experimental animals (32, 33) and humans (34), and consisted mainly of mitochondrial swelling, atrophy, and segmental necrosis. Changes in Z‐band morphology were not commented on in those studies, but close inspection of figures suggest that Z‐band disintegration probably occurred as well.…”

Evaluation of plasma muscle enzyme activity as an indicator of lesion characteristics and prognosis in horses undergoing celiotomy for acute gastrointestinal pain

“…Increased muscle enzyme activity could likely have been attributed to multiple factors resulting in musculoskeletal stress and injury. One suggested mechanisms to account for skeletal muscle injury, and subsequent increases in plasma muscle enzyme activity observed in the present study, includes direct membrane injury by endotoxins and increase in skeletal muscle TNFα and free-radical induced lipid peroxidation, which ultimately lead to cellular dysfunction [27,28]. Metabolic stress induced by the increase in circulating cytokines and endotoxins can lead to an initial hypermetabolic state that quickly exhausts and overwhelms the mitochondria [29].…”

Morphology of cardiac muscle in septic shock. Observations with a porcine septic shock model

“…The findings in the heart are in contrast to the severe damage observed in skeletal muscle where in the early phase, the endothelial cells showed necrosis causing an oedema rich in proteins [7]. Moreover, in the microvasculature of skeletal muscle fibrin thrombi and marked leucocyte sticking were missed.…”

“…We found morpho-logical alterations in endothelial cells indicating a metabolically activated state in the early phase of endotoxin shock. Platelet activating factor and oxygen radicals reduce the anionic charges of endothelial cells [7,26] resulting in a loss of normal permeability of the capillary wall, which facilitates the formation of microthrombi and leads to intracellular oedema of endothelial cells. A prominent feature was marked leucostasis.…”