ArticleThorax2016
Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm.
Article in Thorax, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03201263 (PRessure suppOrT vEntilation + Sigh in aCuTe hypoxemIc respiratOry Failure patieNts), which is not on this map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PRessure suppOrT vEntilation + Sigh in aCuTe hypoxemIc respiratOry Failure patieNts (PROTECTION): a Pilot Randomized Controlled Trial
Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Intraoperative hemidiaphragm electrical stimulation reduces oxidative stress and upregulates autophagy in surgery patients undergoing mechanical ventilation: exploratory study.Journal of translational medicine · 2016Trial
- VIDD or CIADD? The ventilator remains a bona fide culprit.BMC anesthesiology · 2026Article
- The contribution of mechanical ventilation to critical illness-associated diaphragm dysfunction: a critical appraisal.Critical care (London, England) · 2026Review
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.PloS one · 2025Article
- Serial sonographic assessment of diaphragmatic atrophy and lung injury patterns in mechanically ventilated preterm infants to predict extubation failure: a prospective observational study.European journal of pediatrics · 2024Observational
- Diaphragm pacing and independent breathing in individuals with severe Pompe disease.Frontiers in rehabilitation sciences · 2023Article
- Rbm20International journal of molecular sciences · 2022Article
- Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction.Clinical and translational science · 2021Article
- Diaphragmatic dysfunction associated with invasive mechanical ventilation in critically ill adult patientsRevista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2021Article
- Suppression of Hypoxia-Inducible Factor 1α by Low-Molecular-Weight Heparin Mitigates Ventilation-Induced Diaphragm Dysfunction in a Murine Endotoxemia Model.International journal of molecular sciences · 2021Article
- Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome.Journal of clinical medicine · 2021Review
- [Clinical features of sleep-disordered breathing in children with neuromuscular disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Article
- Temporary Transvenous Diaphragmatic Neurostimulation in Prolonged Mechanically Ventilated Patients: A Feasibility Trial (RESCUE 1).Critical care explorations · 2020Article
- Article
- Diaphragm contractile weakness due to reduced mechanical loading: role of titin.American journal of physiology. Cell physiology · 2019Review
- Mechanical ventilation causes diaphragm dysfunction in newborn lambs.Critical care (London, England) · 2019Article
- The effects of fatigue and oxidation on contractile function of intact muscle fibers and myofibrils isolated from the mouse diaphragm.Scientific reports · 2019Article
- Proteomic profiling of the mouse diaphragm and refined mass spectrometric analysis of the dystrophic phenotype.Journal of muscle research and cell motility · 2019Article
- Endurance exercise protects skeletal muscle against both doxorubicin-induced and inactivity-induced muscle wasting.Pflugers Archiv : European journal of physiology · 2019Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundProlonged 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
resultsDiaphragm 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.
conclusionsProlonged 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.