Novel method for transdiaphragmatic pressure measurements in mice

Abstract

The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n=8) and C57BL/6 × 129 (n=9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O2)–hypercapnia (5% CO2), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p=0.001). No difference in Pdi across behaviors was evident between mouse strains (p=0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.

Impact of unilateral denervation on transdiaphragmatic pressure

“…Often DIAm activation during these behaviors is preparatory for expulsive airway clearance, e.g., coughing or sneezing. The Pdi generated during higher force, non-ventilatory behaviors is substantially greater than that generated during ventilatory behaviors (Greising et al, 2013; Mantilla et al, 2010; Sieck and Fournier, 1989; Watchko et al, 1986). For example in cats, mechanical stimulation of the oropharynx induces a gagging/coughing behavior in which Pdi approximates Pdi max (Sieck and Fournier, 1989).…”

“…Measurements of Pdi were performed based on the difference between esophageal and gastric pressures as previously described (Fournier and Sieck, 1988a; Greising et al, 2013; Mantilla et al, 2010; Sassoon et al, 1996; Sieck and Fournier, 1989; Watchko et al, 1986). In anesthetized animals, two 3.5 French Millar solid-state pressure catheters (SPR-524; Millar Instruments, Houston, TX) were inserted through the mouth into the esophagus and stomach, spanning the thoracic and abdominal borders of the DIAm, respectively.…”

“…Previous work from our lab in cats (Fournier and Sieck, 1988b; Sieck and Fournier, 1989), hamsters (Sieck, 1994), rats (Mantilla et al, 2010) and more recently in mice (Greising et al, 2013) used Pdi measurements to estimate DIAm force generation across a range of ventilatory (rhythmic gas exchange) and higher force, non-ventilatory behaviors. In these studies we found that Pdi generated during ventilatory behaviors is consistently less than 50% of maximal Pdi (Pdi max ) elicited by bilateral phrenic nerve stimulation.…”

“…In these studies we found that Pdi generated during ventilatory behaviors is consistently less than 50% of maximal Pdi (Pdi max ) elicited by bilateral phrenic nerve stimulation. For example, Pdi generated during quiet rhythmic breathing (eupnea) ranged from 10–27% of Pdi max depending on species (Greising et al, 2013; Mantilla et al, 2010; Sieck and Fournier, 1989; Watchko et al, 1986). Stimulating breathing by exposure to a hypoxic-hypercapnic (10% O 2 –5% CO 2 ) gas mixture increased Pdi generated during ventilatory behaviors; however, Pdi never exceeded 36% of Pdi max across several species (Greising et al, 2013; Mantilla et al, 2010; Sieck and Fournier, 1989; Watchko et al, 1986).…”

“…The Pdi’s generated during other higher force, non-ventilatory behaviors of the DIAm are also greater than during ventilatory behaviors. For example, during sustained airway occlusion, Pdi ranges from 43–70% of Pdi max across species (Greising et al, 2013; Mantilla et al, 2010; Sieck and Fournier, 1989; Watchko et al, 1986). …”