Increased ventilation caused by improved diaphragmatic efficiency during aminophylline infusion.

The mechanism underlying the increase in ventilation (VE) observed during aminophylline infusion was investigated in 12 anesthetized spontaneously breathing dogs. Progressive doses of aminophylline were infused every 30 min, leading to plasmatic levels of 10 to 20, 20 to 30, 30 to 50 mg/L. The increase in VE observed while increasing aminophylline plasmatic concentration ranged from 4.2 +/- 6 to 9.5 +/- 1.2 L/min. Concomitantly to VE, we measured an index of the inspiratory neuromuscular output of the diaphragm, the transdiaphragmatic pressure generated at FRC 0.1 s after the onset of a spontaneous inspiration developed against closed airways (Pdi0.1). For each plasmatic level of aminophylline, Pdi0.1 increased as VE (117 +/- 4, 126 +/- 2, 140 +/- 6% of control values for 10 to 20, 20 to 30, 30 to 50 mg/L, respectively). To establish the role played by an improvement in diaphragmatic contractility in the increase in Pdi0.1 with aminophylline, we measured for each plasmatic level of aminophylline the transdiaphragmatic pressure generated at FRC against closed airways during supramaximal stimulation at 10, 20, 50, and 100 Hz of the 2 phrenic nerves (Pdi). Pdi increased while increasing aminophylline plasmatic level for all the frequencies of stimulation. A relationship was found between Pdi and Pdi0.1 at any aminophylline plasmatic level as well as with VE. No change in the mechanical properties of the respiratory system occurred with aminophylline. We conclude that the increase in VE observed after aminophylline administration in our animal model is essentially due to an improvement in diaphragmatic contractility rather than an increase in the central nervous system output.