In vivo diaphragm metabolism: Comparison of paced and inspiratory resistive loaded breathing in piglets

Objective: We hypothesized that spontaneous, loaded diaphragm contractions would lead to diaphragm fatigue, which would correlate with inadequate oxidative metabolism as measured by phosphorus-31 nuclear magnetic resonance spectroscopy. Design: Prospective, randomized, crossover trial. Setting: University hospital research laboratory. Subjects: Eight piglets, 4 to 6 wks of age. Interventions: Each animal underwent, in random order, a 20-min period of diaphragm pacing and a 45-min period of loaded spontaneous breathing, separated by a 20-min recovery period. Mechanical Ventilation was used during diaphragm pacing to maintain a Paco(2) of 35 to 45 torr (4.7 to 6.0 kPa) and a Pao(2) of >100 torr (>13.3 kPa). During spontaneous breathing, inspiratory loading was achieved with a 2.0-mm inner diameter endotracheal tube in the breathing circuit. Measurements and Main Results: During pacing, mean transdiaphragmatic pressure decreased by 35%, from 23 +/- 5 (SD) to 15 +/- 3 mm Hg (p <.05), and this decrease correlated with a 335% increase in the ratio of inorganic phosphate to phosphocreatine, from 0.23 +/- 0.1 to 1.0 +/- 0.7 (p <.05). During loaded spontaneous breathing, arterial pH decreased from 7.42 +/- 0.06 to 7.25 +/- 0.05 (p < .05), secondary to an increase in Paco(2) from 41 +/- 4 to 65 +/- 11 torr (5.3 +/- 0.5 to 8.7 +/- 1.5 kPa) (p <.05). Despite respiratory acidosis, there was no decrease in trandiaphragmatic pressure during the period of loaded breathing, nor was any change in the ratio of inorganic phosphate to phosphocreatine seen. Conclusions: Diaphragm fatigue in a pacing model correlates with inadequate oxidative metabolism. In contrast, severe inspiratory resistive loaded breathing did not result in changes in oxidative metabolism or decreased diaphragm force output, despite hypercapnia and respiratory acidosis.