Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
BACKGROUND: Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels.
METHODS AND RESULTS: Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2-4 and 12-74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (Kact), force redevelopment after a shortening protocol (Ktr) and relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed.
CONCLUSIONS: Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Thorax - 71(2016), 5 vom: 15. Mai, Seite 436-45 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hussain, Sabah N A [VerfasserIn] |
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Date Completed 15.09.2016 Date Revised 02.12.2018 published: Print-Electronic CommentIn: Thorax. 2016 May;71(5):397-8. - PMID 27080355 Citation Status MEDLINE |
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| doi: |
10.1136/thoraxjnl-2015-207559 |
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NLM258962585 |
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| 100 | 1 | |a Hussain, Sabah N A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Completed 15.09.2016 | ||
| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Thorax. 2016 May;71(5):397-8. - PMID 27080355 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ | ||
| 520 | |a BACKGROUND: Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels | ||
| 520 | |a METHODS AND RESULTS: Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2-4 and 12-74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (Kact), force redevelopment after a shortening protocol (Ktr) and relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed | ||
| 520 | |a CONCLUSIONS: Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Assisted Ventilation | |
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| 700 | 1 | |a Leite, Felipe de Souza |e verfasserin |4 aut | |
| 700 | 1 | |a Petrof, Basil J |e verfasserin |4 aut | |
| 700 | 1 | |a Mofarrahi, Mahroo |e verfasserin |4 aut | |
| 700 | 1 | |a Moroz, Nikolay |e verfasserin |4 aut | |
| 700 | 1 | |a de Varennes, Benoit |e verfasserin |4 aut | |
| 700 | 1 | |a Goldberg, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Rassier, Dilson E |e verfasserin |4 aut | |
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