Tumor necrosis factor α decreases in vivo diaphragm contractility in dogs

In this study, we hypothesized that tumor necrosis factor α (TNFα) is an important mediator of sepsis-related impairment in diaphragm contractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimulating electrodes were placed on the phrenic nerves and diaphragm electromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmatic pressure (Pdi) was also recorded using esophageal (Pes) and abdominal balloon catheters (Pdi = Pab - Pes). Dogs were randomized to receive saline injection (n = 6), or TNFα 60 μg/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNFα animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNFα infusion (p < 0.05) and remained at greater than baseline values at study termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNFα infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNFα animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNFα infusion was associated with significant declines in isotonic and quasi-isometric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.