INCREASED VENTILATION CAUSED BY IMPROVED DIAPHRAGMATIC EFFICIENCY DURING AMINOPHYLLINE INFUSION

Abstract

The mechanism underlying the increase in ventilation (.ovrhdot.VE) observed during aminophylline infusion was investigated in 12 anesthetized, spontaneously breathing dogs. Progressive doses of aminophylline were infused every 30 min, leading to plasma levels of 10-20, 20-30, 30-50 mg/l. The increase in .ovrhdot.VE observed while increasing aminophylline plasma-concentration ranged from 4.2 .+-. 6 to 9.5 .+-. 1.2 l/min. An index was also measured of the inspiratory neuromuscular output of the diaphragm, the transdiaphragmatic pressure generated at FRC [functional residual capacity] 0.1 s after the onset of a spontaneous inspiration developed against closed airways .**GRAPHIC**. For each plasma level of aminophylline, .**GRAPHIC**. increased as .ovrhdot.VE (117 .+-. 4, 126 .+-. 2, 140 .+-. 6% of control values for 10-20, 20-30, 30-50 mg/l, respectively). To establish the role played by an improvement in diaphragmatic contractility in the increase in .**GRAPHIC**. with 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) was measured for each plasma level of aminophylline. PDi increased while increasing aminophylline plasma level for all the frequencies of stimulation. A relationship was found between Pdi and .**GRAPHIC**. at any aminophylline plasma level and with .ovrhdot.VE. No change in the mechanical properties of the respiratory system occurred with aminophylline. The increase in .ovrhdot.VE observed after aminophylline administration in this animal model is essentially due to an improvement in diaphragmatic contractility rather than an increase in CNS output.