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Published on: September 19, 2025
Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats
Dries Testelmans1, Karen Maes, Patrick Wouters
1Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, Leuven, Belgium.
Objective:
Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin- proteasome pathway.
Design:
Randomized, controlled experiment.
Setting:
Basic animal science laboratory.
Subjects:
Male Wistar rats, 14 wks old.
Interventions:
Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium.
Measurements And Main Results:
In vitro diaphragm force was decreased more significantly after 24 hrs of mechanical ventilation combined with rocuronium infusion than after mechanical ventilation alone (e.g., tetanic force, -27%; p < .001 vs. mechanical ventilation). Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (-38% and -29%, respectively; p < .001 vs. control). Diaphragm hydroperoxide levels increased similarly in both mechanically ventilated groups. Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin-proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control). Significant correlations were found between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber dimensions.
Conclusions:
Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin-proteasome pathway. These findings could be important with regard to weaning failure in patients receiving this drug for prolonged periods in the intensive care unit setting.
Insights
Rocuronium infusion during mechanical ventilation worsens diaphragm function and muscle fiber atrophy. This suggests increased activation of the ubiquitin-proteasome pathway, potentially impacting patient recovery.
Area of Science:
- Intensive care medicine
- Respiratory physiology
- Molecular biology
Background:
- Nondepolarizing neuromuscular blocking agents are used in intensive care.
- These agents can cause myopathy.
- Mechanical ventilation can lead to diaphragmatic atrophy and reduced force.
Purpose of the Study:
- To investigate the effects of rocuronium infusion during mechanical ventilation on diaphragm function.
- To determine if rocuronium enhances the ubiquitin-proteasome pathway activation in the diaphragm.
Main Methods:
- A randomized, controlled animal experiment was conducted.
- Male Wistar rats were divided into four groups: control, spontaneous breathing, mechanical ventilation with saline, and mechanical ventilation with rocuronium.
- Diaphragm function, fiber dimensions, and ubiquitin-proteasome pathway activation (MURF-1 mRNA) were assessed after 24 hours.
Main Results:
- Mechanical ventilation with rocuronium significantly decreased in vitro diaphragm force compared to mechanical ventilation alone.
- Rocuronium exacerbated atrophy of diaphragm type IIx/b fibers.
- Diaphragm MURF-1 mRNA expression, an indicator of the ubiquitin-proteasome pathway, increased significantly with rocuronium combined with mechanical ventilation.
Conclusions:
- Rocuronium infusion during mechanical ventilation further impairs diaphragm function and increases muscle fiber atrophy.
- These effects are associated with enhanced activation of the ubiquitin-proteasome pathway.
- Findings suggest rocuronium may contribute to weaning failure in critically ill patients.
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