Understanding critical illness myopathy: approaching the pathomechanism.
Myopathies occurring in critically ill patients have gained increasing interest during the past years. For the patient, they represent a crucial factor for prolonged intensive care unit treatment and secondary complications. Critical illness myopathies (CIMs) seem to be related to various pathogenic factors. Among those, the septic inflammatory response syndrome seems to play a major role. It has been suggested that, similar to sepsis-related multiorgan failure, CIM might be considered a failure of the organ muscle. Muscle function might be impaired by proposed "myotoxic" humoral factors. These could be endogenously produced during the innate immune response to sepsis. This article follows up recent evidence for such active fractions in the blood serum of CIM patients. To explain muscle weakness in CIM, serum fractions acutely modified membrane excitability and subcellular Ca2+ regulation in an animal model. From the differential serum effects, early-phase CIM seems to involve a reduction in the overall force generation in muscle but also a compensation by the membrane, increasing the excitability. Different animal models will help to elucidate the underlying mechanisms accounting for the specific proteolytic activities found in different forms of CIM. CIM represents a systemic rather than a local disorder. Humoral factors might initiate the local reaction of skeletal muscle clinically seen as muscle weakness, altered excitability, and proteolysis of contractile proteins. Establishing the interactions in the excitation-contraction cascade in CIM is a challenging task, not only to clarify its pathomechanism but also to deduce clinical interventions.
Medical Biophysics, Institute of Physiology & Pathophysiology, University of Heidelberg, INF 326, 69120 Heidelberg, Germany. oliver.friedrich@urz.uni-heideberg.de
Oliver
O
Friedrich
Rainer H A
RH
Fink
Ernst
E
Hund
D000818:Animals; D016638:Critical Illness; D006801:Humans; D023421:Models, Animal; D018908:Muscle Weakness; D018482:Muscle, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000209:etiology / Q000473:pathology*