Respiratory muscle injury in animal models and humans

Respiratory muscle injury may result from excessive loading due to a decrease in respiratory muscle strength, an increase in the work of breathing, or an increase in the rate of ventilation. Other conditions such as hypoxemia, hypercapnia, aging, decreased nutrition, and immobilization may potentiate respiratory muscle injury. Respiratory muscle injury has been shown in animal models using direct muscle or phrenic nerve stimulation, acute inspiratory resistive loading, tracheal banding, corticosteroids, phrenic nerve section, and the mdx mouse. Although numerous examples of diaphragm injury have been shown in animal models, evidence in humans is sparse. Potential mechanisms which may contribute to respiratory muscle injury include high levels of intracellular calcium-activated degradative enzymes, non-uniformity of stresses and strains, plasma membrane disruptions, and activation of the inflammatory process.