Nicola Cacciani1, Hannah Ogilvie2, Lars Larsson3. 1. Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Sweden. Electronic address: Nicola.cacciani@neuro.uu.se. 2. Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Sweden. Electronic address: Hannah.ogilvie@neuro.uu.se. 3. Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Sweden; Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, USA. Electronic address: Lars.larsson@neuro.uu.se.
Abstract
BACKGROUND: Critically ill intensive care patients are subjected to controlled mechanical ventilation (CMV) which has an important association in triggering the impaired muscle function and the consequent delayed weaning from the respirator. AIM: The main aim of this study was to measure the effects of age and CMV over a period up to 5days on rat diaphragm muscle fibers, more specifically focusing on the changes in fiber structure and function. METHODS: Diaphragm muscle fiber cross-sectional area (CSA) and force generating capacity were measured in young (6months) and old (28-32months) rats in response to five days of CMV. To investigate the biological age of the old rats in this rat strain (F344 BN hybrid), a second set of experiments comparing muscle fiber size and specific force (maximum force normalized to CSA) was investigated in fast- and slow-twitch distal hind limb muscles in 3 different age groups: young adults (6months), middle aged (18months) and old rats (28months). RESULTS: This study shows an unexpected response of the diaphragm fibers to 5days CMV, demonstrating an increased CSA (p<0.001) in both young and old animals. Furthermore, an observed decreased maximum force of 39.8-45.2% (p<0.001) in both young and old animals compared with controls resulted in a dramatic loss of specific force. We suggest that this increase in CSA and decrease in specific force observed in both the young and old diaphragm fibers is an ineffective compensatory hypertrophy in response to the CMV. These results demonstrate an important mechanism of significant importance for the weaning problems associated with mechanical ventilation.
BACKGROUND: Critically ill intensive care patients are subjected to controlled mechanical ventilation (CMV) which has an important association in triggering the impaired muscle function and the consequent delayed weaning from the respirator. AIM: The main aim of this study was to measure the effects of age and CMV over a period up to 5days on rat diaphragm muscle fibers, more specifically focusing on the changes in fiber structure and function. METHODS: Diaphragm muscle fiber cross-sectional area (CSA) and force generating capacity were measured in young (6months) and old (28-32months) rats in response to five days of CMV. To investigate the biological age of the old rats in this rat strain (F344 BN hybrid), a second set of experiments comparing muscle fiber size and specific force (maximum force normalized to CSA) was investigated in fast- and slow-twitch distal hind limb muscles in 3 different age groups: young adults (6months), middle aged (18months) and old rats (28months). RESULTS: This study shows an unexpected response of the diaphragm fibers to 5days CMV, demonstrating an increased CSA (p<0.001) in both young and old animals. Furthermore, an observed decreased maximum force of 39.8-45.2% (p<0.001) in both young and old animals compared with controls resulted in a dramatic loss of specific force. We suggest that this increase in CSA and decrease in specific force observed in both the young and old diaphragm fibers is an ineffective compensatory hypertrophy in response to the CMV. These results demonstrate an important mechanism of significant importance for the weaning problems associated with mechanical ventilation.