Effects of digoxin on diaphragmatic strength generation

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Abstract
Contrary to hindlimb muscle, extracellular calcium plays an important role in diaphragmatic strength generation (J. Appl. Physiol. 58: 2054-61, 1985). Since the inotropic effect of digitalis appears to be related to cell membrane transport of calcium, we studied the effect of digoxin on diaphragmatic contractility in 20 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters at functional residual capacity. Cardiac output was measured with a Swan-Ganz catheter and diaphragmatic blood flow (Qdi) by timed volume collections of left inferior venous effluent. The force generated by the sartorius muscle during electrical stimulations was studied concomitantly to Pdi. In 10 dogs (group A) 0.04 mg/kg of digoxin was infused in 10 min. In 10 other dogs (group B) 0.2 mg/kg was administered. All measurements were performed during control and 30, 60, 90, and 120 min after digoxin administration. In group A, digoxin plasmatic level at 60 min reached a therapeutic range in all dogs (1.8 .+-. 0.3 ng/ml), whereas in group B, digoxin plasmatic level was higher (8 .+-. 1.3 ng/ml). No significant change in cardiac output and Qdi was noted after administration of digoxin, either in the dogs of group A or those of group B. Digoxin had an important positive inotropic effect on the diaphragm of the two groups of dogs, with a mean increase in Pdi in group A of 27 .+-. 4, 27.5 .+-. 5, 21 .+-. 4, and 24.5 7U 4 and in group B of 38 .+-. 5, 45.4 .+-. 6, 41 .+-. 5, and 33.5 .+-. 5% of control values (P < 0.001 for each value) at 10, 20, 50, and 100 Hz, respectively. Contrary to the diaphragm, the force generated by the sartorius muscle was not affected by digoxin administration for any frequencies of stimulation in group A or in group B. We conclude that digoxin enhances diaphragmatic strength, whereas it has no effect on the sartorius. These results open new insights on the mechanisms of diaphragmatic contraction, notably by underlying the particularity of the diaphragm among the other striated skeletal muscles.