Inflammation and immobility are comorbid etiological factors inducing muscle weakness in critically ill patients. This study establishes a rat model to examine the effect of inflammation and immobilization alone and in combination on muscle contraction, histology, and acetylcholine receptor regulation.
Prospective, randomized, experimental study.
Animal laboratory of a university hospital.
To produce systemic inflammation, rats (n = 34) received three consecutive intravenous injections of Corynebacterium parvum on days 0, 4, and 8. Control rats (n = 21) received saline. Both groups were further divided to have one hind limb either immobilized by pinning of knee and ankle joints or sham-immobilized (surgical leg). The contralateral nonsurgical leg of each animal served as control (nonsurgical leg).
After 12 days, body weight and muscle mass were significantly reduced in all C. parvum animals compared with saline-injected rats. Immobilization led to local muscle atrophy. Normalized to muscle mass, tetanic contraction was reduced in the surgical leg after immobilization (7.64 ± 1.91 N/g) and after inflammation (8.71 ± 2.0 N/g; both p < .05 vs. sham immobilization and saline injection, 11.03 ± 2.26 N/g). Histology showed an increase in inflammatory cells in all C. parvum–injected animals. Immobilization in combination with C. parvum injection had an additive effect on inflammation. Acetylcholine receptors were increased in immobilized muscles and in all muscles of C. parvum–injected animals.
The muscle weakness in critically ill patients can be replicated in our novel rat model. Inflammation and immobilization independently lead to muscle weakness.
From the Klinik für Anaesthesiologie (HF, MH, CU, MB), Institut für Experimentelle Onkologie und Therapieforschung (AL), and Institut für Pathologie und pathologische Anatomie (FN) der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany; and the Department of Anesthesia and Critical Care, Shriners Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA (JAJM).
The authors have not disclosed any potential conflicts of interest.
Supported, in part, by grant 56-03 from the Kommission für klinische Forschung, Klinikum rechts der Isar, Munich, Germany (Dr. Fink); grants 8530, 8740, and 8891 from Shriners Hospital for Children, Tampa, FL (Dr. Martyn); and grants GM31569, GM21500-Project IV, and 55082 from the National Institutes of Health, Bethesda, MD (Dr. Martyn).
For this research, Dr. Fink was awarded the 2004 Young Investigator Award by the American Society of Critical Care Anesthesiologists.
The work was performed at Klinik für Anaesthesiologie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany, and the Department of Anesthesia and Critical Care, Shriners Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA.
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