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Long-term use of mechanical ventilation contributes to the deterioration of human diaphragm muscle
March 27, 2008Penn study suggests blocking the molecular atrophy pathway to help safely wean patients off ventilators
PHILADELPHIA - A new study by University of Pennsylvania School of Medicine shows, for the first time in humans, that ventilators combined with diaphragm disuse contributes to muscle atrophy in the diaphragm in as little as eighteen hours. Muscle atrophy in the diaphragm is a major contributor of why patients who have undergone prolonged mechanical ventilation often have difficulty breathing after being removed from the ventilator.
The report, published in the March 27th edition of the New England Journal of Medicine, measured a greater than 50 percent decline in muscle fibers in the diaphragm. In addition, the study measured the proteins that play a key role in the muscle-wasting chemical cascade. By intervening in this pathway, the research suggests, a new pharmacological approach to safely and quickly wean patients off ventilators could be developed.
Sanford Levine, PhD, Professor of Thoracic Surgery and co-director of the Respiratory Muscle Research Laboratory, led a team that conducted 22 biopsies on both deceased and living patients. Fourteen brain-dead organ donors, aged 18 to 58, comprised the case study with each having undergone between 18 and 69 hours of mechanical ventilation. The eight-member control group each received less than three hours.
Levine said both groups were demographically and statistically similar except for the time each had spent on mechanical ventilation. Biopsy results on the other hand were different.
Compared to the control group, the diaphragms of the 14 case study members revealed:
* 23 percent lower levels of the free-radical fighting antioxidant, glutathione
* 154 percent more Caspase-3, a calcium-dependant "executioner" enzyme that degrades protein molecules and is responsible for programmed cell deaths
* Muscle-wasting Atrogin-1 genes at a ratio of 200:1 over MBD4 housekeeper genes that maintain healthy cells
* MURF-1 nucleotides that attack myofiber proteins at a ratio of 590:1 over housekeeper genes
"From our observations, we conclude that these (biopsy differences) could only be attributed to marked atrophy caused by a combination of complete diaphragm inactivity and mechanical ventilation," Levine said.
"Disuse atrophy of human diaphragm myofibers could be a major contributor to the weaning problems that occur in some of our patients," Levine said. "Therefore, we believe fiber atrophy of the magnitude noted in our case diaphragms could have clinical significance."
University of Pennsylvania School of Medicine
Sanford Levine, PhD, Professor of Thoracic Surgery and co-director of the Respiratory Muscle Research Laboratory, led a team that conducted 22 biopsies on both deceased and living patients. Fourteen brain-dead organ donors, aged 18 to 58, comprised the case study with each having undergone between 18 and 69 hours of mechanical ventilation. The eight-member control group each received less than three hours.
Levine said both groups were demographically and statistically similar except for the time each had spent on mechanical ventilation. Biopsy results on the other hand were different.
Compared to the control group, the diaphragms of the 14 case study members revealed:
* 23 percent lower levels of the free-radical fighting antioxidant, glutathione
* 154 percent more Caspase-3, a calcium-dependant "executioner" enzyme that degrades protein molecules and is responsible for programmed cell deaths
* Muscle-wasting Atrogin-1 genes at a ratio of 200:1 over MBD4 housekeeper genes that maintain healthy cells
* MURF-1 nucleotides that attack myofiber proteins at a ratio of 590:1 over housekeeper genes
"From our observations, we conclude that these (biopsy differences) could only be attributed to marked atrophy caused by a combination of complete diaphragm inactivity and mechanical ventilation," Levine said.
"Disuse atrophy of human diaphragm myofibers could be a major contributor to the weaning problems that occur in some of our patients," Levine said. "Therefore, we believe fiber atrophy of the magnitude noted in our case diaphragms could have clinical significance."
University of Pennsylvania School of Medicine
Muscle Atrophy Current Events and Muscle Atrophy News RSSScientists discover clues to what makes human muscle age
A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself.
Mutation responsible for cystic fibrosis also involved in muscle atrophy
Patients with cystic fibrosis (CF) usually experience significant muscle loss, a symptom traditionally considered to be a secondary complication of the devastating genetic disease.
Peripheral nerve repair with fat precursor cells led to wider nerves and less muscle atrophy
To determine if guided fat (adipose) precursor cells (APCs) could improve nerve regeneration and functional recovery, researchers at the University of Pittsburgh (USA) used biodegradable nerve guides to transplant APCs into the injured peripheral nerves of laboratory rats.
Muscle atrophy through thick but not thin
During desperate times, such as fasting, or muscle wasting that afflicts cancer or AIDS patients, the body cannibalizes itself, atrophying and breaking down skeletal muscle proteins to liberate amino acids.
As Good As It Gets: Octogenarian Muscles Don't Get Stronger With Exercise
Octogenarian women were unable to increase muscle mass after a 3-month weight lifting program targeted at strengthening the thigh muscle, according to a new study from the Journal of Applied Physiology.
Researchers genetically link Lou Gehrig's disease in humans to dog disease
An incurable, paralyzing disease in humans is now genetically linked to a similar disease in dogs. Researchers from the University of Missouri and the Broad Institute have found that the genetic mutation responsible for degenerative myelopathy (DM) in dogs is the same mutation that causes amyotrophic lateral sclerosis (ALS), the human disease also known as Lou Gehrig's Disease.
Motor neuron disease and toxic substances: Possible link?
Motor neuron disease is a rare, devastating illness in which nerve cells that carry brain signals to muscles gradually deteriorate. One form of it, Lou Gehrig's disease or ALS (amyotrophic lateral sclerosis), is familiar to the public in the lives of scientist Stephen Hawking and Morrie Schwartz, about whom Mitch Albom's "Tuesdays with Morrie" was written.
After successfully delivering Columbus, Atlantis is back on Earth
NASA's space shuttle Atlantis, which successfully delivered ESA's Columbus laboratory to the International Space Station, has safely returned to Earth with its crew of seven. Landing was at 14:07 UTC (15:07 CET) on 20 February at Kennedy Space Center, Florida.
Scientists identify gene responsible for statin-induced muscle pain
Statins, the popular class of drugs used to lower cholesterol, are among the most commonly prescribed medications in developed countries.
Energy supplement under study for Parkinson's disease
Whether a supplement used by athletes to boost energy levels and build muscle can slow progression of Parkinson's disease is the focus of a North American study.
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