Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. Currently research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To better understand the mechanism underlying reduced firing motor unit firing rates we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW.
- action potential
- critical illness myopathy
- critical illness neuropathy
- motor neuron
- Copyright © 2012, Journal of Neurophysiology