How titin affects diaphragm weakness during ventilator use
Official title: Role of titin in the pathophysiology of diaphragm weakness during mechanical ventilation
Funded at University of Arizona · NIH-11192344 · Data updated 2026-11-12
This project looks at whether changes in the muscle protein titin make the breathing muscle (diaphragm) weaker in people on mechanical ventilators.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Arizona NIH-funded |
| Lab location | 1 site (Tucson, United States) |
| Project start | January 1, 2014 |
| Project end | July 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $586,463 |
| NIH project number | 5R01HL121500-12 |
| Project ID | NIH-11192344 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults in the ICU who are receiving mechanical ventilation and can safely provide consent (or have a proxy consent) and undergo a diaphragm biopsy would be the ideal candidates.
✕Less likely to help
People who are not on mechanical ventilation or whose breathing problems come from non-muscular causes are unlikely to benefit directly from this research.
What this research studies
If you or a loved one is in the ICU on a ventilator, researchers will study small diaphragm tissue samples to understand why the breathing muscle weakens quickly when it is unloaded. They will measure how the main muscle proteins (myosin and actin) behave and whether titin helps release myosin from an inactive state. The team combines muscle-force testing with X-ray diffraction and biochemical assays on patient biopsy samples. Their approach aims to map the chain of events that leads to ventilator-induced diaphragm weakness.
Why it matters
Potential benefit: If successful, this work could point to new ways to prevent or reverse diaphragm weakness in ventilated patients and help more people come off ventilators safely.
How similar studies have gone: Laboratory and pilot biopsy data support a role for the myosin 'super-relaxed' state and titin in diaphragm weakness, but translating these findings into therapies is still novel.
Where this research is happening
-
University of Arizona
Tucson, United States Active
Researchers
- Principal investigator: Ottenheijm, Coen — University of Arizona
- Study coordinator: Ottenheijm, Coen
Related research
Other NIH-funded projects on the same topics.
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Advancing Acute Respiratory Infection Care for Kids on Home Ventilators
This grant aims to improve how doctors and families manage acute respiratory infections in children who rely on invasive long-term home ventilation.
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A Tablet-Based Emotion Regulation Program for Surrogate Decision-Makers of ICU Patients on Ventilation
A randomized trial tests a brief tablet program to help people who decide for ICU patients on ventilation feel less anxious and make better decisions.
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Optimizing pain relief for children on mechanical ventilation
A large, multi-site trial tests whether adding non-opioid pain medicines to standard opioid care can reduce pain and lower opioid use in children on breathing machines in PICUs.
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Role of titin in diaphragm weakness during mechanical ventilation
This grant studies how the diaphragm’s core proteins work together, especially titin and myosin, to understand why diaphragm weakness happens during mechanical ventilation.
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Time-limited trials to guide invasive ventilation decisions
A scientific team is testing how short, structured trials of life-support in ICU patients with acute respiratory failure can help patients and families choose the best path.
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How breathing machines can harm the kidneys
Doctors will look at how ventilators change kidney filtering and salt handling in people who are critically ill to help prevent kidney damage.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.