Effects of aminophylline and salbutamol on diaphragmatic force during compensated metabolic acidosis

We investigated the effects of aminophylline and salbutamol on tetanic force generated by the diaphragm during compensated metabolic acidosis in dogs. Anesthetized, mechanically ventilated animals were prepared with an open thorax. A cast was placed around the abdomen to maintain length and geometry of the diaphragm during contractions. A thin-walled latex balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi). Pdi served as the index of diaphragmatic force of contraction. We measured Pdi during supramaximal phrenic stimulation at low and high frequencies and also during spontaneous inspiratory efforts for a constant diaphragmatic EMG activity. Compensated metabolic acidosis significantly reduced Pdi at all stimulation frequencies (p < 0.05). The mean percent decrease at low frequencies was greater than at high (p < 0.05). Pdi was decreased during spontaneous contractions as well (p < 0.05). Administration of aminophylline significantly improved Pdi at all frequencies of phrenic stimulation (p < 0.05) and during spontaneous inspiratory efforts (p < 0.05). Infusion of salbutamol did not have a significant effect on Pdi at any frequency of stimulation but did produce a small potentiating effect during spontaneous contractions (p < 0.05). We also recorded and analyzed the Pdi response to a single supramaximal impulse to the phrenic nerve, referred to as a twitch, to gain insight into possible cellular mechanisms underlying alterations in tetanic force of contraction. Compensated metabolic acidosis led to a significant reduction in peak twitch tension (PTT) (p < 0.05) and half relaxation time (1/2RT) (p < 0.05). Administration of aminophylline restored PTT and 1/2RT to control values (p < 0.05). Infusion of salbutamol also restored PTT to control values (p < 0.05) but did not have an effect on the shortened 1/2RT. We conclude that during compensated metabolic acidosis, aminophylline markedly improves tetanic force generated by the diaphragm, whereas salbutamol has a much smaller effect.