Diaphragm vascular structure and function: Health, disease, and exercise

As the primary inspiratory muscle, the diaphragm is paramount for mammalian survival, with diaphragm contraction representing the essential first step in delivering oxygen to the circulation. Previous studies have demonstrated that the diaphragm is an extraordinary and highly plastic muscle that adapts to physiological (e.g., exercise) and pathophysiological (e.g., augmented work associated with disease) changes in metabolic demand. In recent years, preclinical investigations have revealed that vasomotor responsiveness and vascular control mechanisms in the diaphragm differ from the established mechanisms in locomotor skeletal muscle in both health and disease. With aging and across several pathologies that compromise diaphragm contractile function (e.g., heart failure, emphysema, and pulmonary hypertension), our knowledge regarding the plasticity of the diaphragm vasculature is still in its infancy. Further, the integration of mechanistic preclinical studies and emerging novel human investigations using state-of-the-art technology (e.g., contrast-enhanced ultrasound) is imperative to advance our understanding of diaphragm vascular dysfunction and aid in the development of targeted strategies to improve diaphragm hemodynamics and contractile function and lessen the burden of respiratory muscle failure. The objective of this review is to synthesize the most up-to-date literature regarding diaphragm vasomotor control in health, disease, and exercise, most of which comes from preclinical investigations, and to provide insights into promising future research directions.