Functional Measurement of Respiratory Muscle Motor Behaviors Using Transdiaphragmatic Pressure

Abstract

The diaphragm muscle must be able to generate sufficient forces to accomplish a range of ventilatory and non-ventilatory behaviors throughout life. Measurements of transdiaphragmatic pressure (Pdi) can be conducted during eupnea, hypoxia (10% O2)-hypercapnia (5% CO2), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths (i.e., sighs), sustained airway or tracheal occlusion, and maximal efforts elicited via bilateral phrenic nerve stimulation, representing the full range of motor behaviors available by the diaphragm muscle. We provide detailed methods on the in vivo measurements of Pdi in mice.

Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness

“…; Greising et al . ). By contrast, we hypothesized that non‐ventilatory behaviours, such as airway obstruction, airway clearance, and respiratory reflexes encompassing coughing and sneezing, requiring substantially elevated respiratory muscle activation, and which are critical for the safeguarding of pulmonary function, are compromised in dystrophic disease.…”

“…), producing up to 50% of peak transdiaphragmatic pressure in mice (Greising et al . ; ; ). Interestingly, during augmented breaths, peak inspiratory oesophageal pressure generation was preserved and significantly greater in mdx compared to wild‐type mice, again convincingly demonstrating a lack of mechanical constraint in 8‐week‐old mdx mice despite substantial diaphragm weakness (approaching 50% force loss compared with wild‐type in the range 60–100 Hz).…”

“…), including studies in mice (Greising et al . , , ), and these behaviours can be adequately met even in the context of motor neuron loss (Khurram et al . ) or age‐related sarcopenia of the diaphragm (Khurram et al .…”

Diaphragm Muscle Adaptation to Sustained Hypoxia: Lessons from Animal Models with Relevance to High Altitude and Chronic Respiratory Diseases

“…The diaphragm has a considerable functional reserve capacity which can be readily observed through reflex hyperventilation in response to hypoxic insult in order to limit oxygen desaturation in arterial blood, and especially during maximal activation during airway blockage or reflex behaviors such as cough and sneeze (Brown et al, 2014; Greising et al, 2016). Sustained hypoxia weakens the diaphragm (Shiota et al, 2004; Degens et al, 2010; McMorrow et al, 2011; Lewis et al, 2016), potentially priming an inability to cope with further increases in workload as may occur in exacerbations of chronic respiratory diseases, contributing to disease progression.…”

Respiratory muscle dysfunction in animal models of hypoxic disease: antioxidant therapy goes from strength to strength

“…The high oxidative capacity of the diaphragm muscle fibers7,8 confers considerable fatigue resistance, a useful trait for the most active striated muscle in the body. Fast glycolytic fibers are also present7,8 and are recruited for near-maximal activation during airway obstruction, sneezing, and exacerbations of chronic respiratory disease 9,10. In contrast, upper airway dilator muscles are characterized by a predominant expression of fast glycolytic fibers,11,12 which may be important in preventing/overcoming pharyngeal collapse and maintaining airway patency in addition to nonrespiratory functions in deglutition and speech 5,6.…”