The dose?response relationship of amrinone in increasing the contractility of fatigued diaphragm in dogs

Abstract

We studied the dose-related effects of amrinone on the contractility of a fatigued diaphragm in 16 anesthetized, mechanically ventilated dogs. The animals were divided into two groups: the control group (Group C, n = 8) and the amrinone group (Group A, n = 8). Diaphragmatic fatigue was induced by intermittent supramaximal bilateral elec- trophrenic stimulation at a frequency of 20 Hz applied for 30min. The contractility of the diaphragm was assessed from changes in transdiaphragmatic pressure (Pai). After inducing fatigue, Pd~ at low-frequency (20Hz) stimulation decreased significantly compared with the pre-fatigue values (P < 0.05), whereas no change was observed at high-frequency (100Hz) stimulation. In Group A, after producing fatigue, P< at 20Hz stimulation increased significantly with a bolus injection (0.75 mg.kg 1) followed by continuous infusion of amrinone (2.5, 5 and then 10vg.kg-l.min ~) IV (P < 0.05). Pdi at 100Hz stimulation increased significantly with an administration of amrinone (10~g.kg-a.min a) IV (P < 0.05). There was a sig- nificant positive correlation between Pd~ at both stimuli and amrinone dose (P < 0.01). In Group C, the speed of recovery of P~i at 20Hz stimulation was relatively slower. The inte- grated electric activity of the diaphragam (Edi) in each group did not change at any frequency of stimulation throughout the experiment. We conclude that amrinone exerts a dose- dependent enhancement of the contractility of a fatigued diaphragm in dogs.