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Published on: February 25, 2015
Leupeptin inhibits ventilator-induced diaphragm dysfunction in rats
Karen Maes1, Dries Testelmans, Scott Powers
1Respiratory Muscle Research Unit, Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.
American Journal of Respiratory and Critical Care Medicine
|March 24, 2007
Summary
Leupeptin, a protease inhibitor, completely prevented diaphragm dysfunction and atrophy caused by controlled mechanical ventilation (CMV). This finding highlights the role of proteolysis in ventilation-induced diaphragm injury.
Area of Science:
- Physiology
- Biochemistry
- Cell Biology
Background:
- Controlled mechanical ventilation (CMV) can lead to diaphragmatic proteolysis, atrophy, and contractile dysfunction.
- Proteolytic pathways, including lysosomal proteases and calpain, are implicated in these detrimental effects.
Purpose of the Study:
- To investigate if leupeptin, a protease inhibitor, can protect the diaphragm from mechanical ventilation-induced damage.
- To assess the impact of leupeptin on diaphragmatic proteolysis, atrophy, and contractile function during CMV.
Main Methods:
- Rats were subjected to 24 hours of CMV.
- Animals received either saline or leupeptin (15 mg/kg) via intramuscular injection during ventilation.
- Diaphragm-specific force production, fiber atrophy, and protease activities (cathepsin B, calpain) were measured.
Main Results:
- CMV significantly reduced diaphragm force production, an effect completely prevented by leupeptin.
- Leupeptin prevented atrophy of type IIx/b muscle fibers observed after CMV.
- CMV increased cathepsin B and calpain activities, which was abolished by leupeptin treatment.
- Diaphragmatic force generation inversely correlated with cathepsin B and calpain activity.
Conclusions:
- Leupeptin administration effectively prevented diaphragmatic contractile dysfunction and atrophy induced by mechanical ventilation.
- Inhibiting specific proteases like cathepsin B and calpain offers a protective strategy against ventilation-induced diaphragm injury.
