Diaphragm Blood Flow: New Avenues for Human Translation.

The rhythmic contraction of the diaphragm facilitates continuous pulmonary ventilation essential for life. Adequate blood flow to the diaphragm is critical to continuously support contractile function, as an imbalance in nutritive supply and demand can lead to diaphragm insufficiency, patient morbidity and mortality. Given oxygen supply to the diaphragm is key to its function, it is no surprise that more than 200 animal studies have investigated diaphragm blood flow (Q̇) regulation over the past century. This work has advanced our understanding of the diaphragm's circulatory control (, regional blood flow heterogeneity, mechanical impediment) and response to a variety of conditions, including eupnea, exercise, hypoxia, hypercapnia, hemorrhage, mechanical ventilation, and pharmacological interventions. However, due to the relative inaccessibility of the diaphragm, few studies have been conducted in humans since Q̇ measurements have historically required highly invasive and technically challenging techniques that are not conducive to routine use. Thus, our current understanding of Q̇ is informed almost exclusively by animal work with conflicting findings and its translation to humans is hindered by species-dependent variability in diaphragmatic structure and function. Novel approaches have been developed to quantify respiratory muscle blood flow in humans using minimally invasive techniques. More recently, contrast-enhanced ultrasound (CEUS), is a promising approach for quantifying Q̇ in humans, independent from other respiratory muscles. Using novel approaches to quantify Q̇ in humans, future research can aim to advance our understanding of Q̇ in humans in health and disease, including exercise, sex-based comparisons, and critical care.