Diaphragm Muscle Weakness
The Mayo Clinic Cell and Regenerative Physiology Laboratory is examining basic mechanisms underlying muscle fiber atrophy and weakness in a variety of conditions.
Diaphragm muscle weakness is a hallmark of a number of diseases, such as neurodegenerative diseases and chronic obstructive pulmonary disease; conditions, such as hypothyroidism, cachexia and sarcopenia; and treatments, such as mechanical ventilation, corticosteroids and chemotherapy. Such weakness, when it occurs, may severely limit the mechanical performance of the diaphragm and compromise the ability to clear the airways or, under extreme conditions, the ability to breathe.
Dr. Sieck's research team is focusing on the basic unit of mechanical force in muscle fibers — the cross-bridge. At the molecular level, Dr. Sieck explores the excitation-contraction coupling, mechanics and energetics of four different types of myosin heavy chains that compose different muscle fiber types.
Dr. Sieck's laboratory has discovered fiber type differences in cross-bridge cycling kinetics and the mechanical and energetic consequence of changes in myosin heavy chain expression and content in diaphragm muscle fibers. Dr. Sieck's research clearly implicates fiber type differences in the impact of diseases, conditions and treatments on myosin heavy chain expression that impacts muscle fiber cross-bridge cycling resulting in muscle weakness.
For example, Dr. Sieck's lab is exploring sarcopenia, the age-related atrophy and weakening of muscle fibers. Specifically, in the diaphragm muscle, sarcopenia affects respiratory neuromotor control. These studies will provide potential therapeutic targets to mitigate the functional impact of sarcopenia, improving quality of life in older adults.