TUMOR-NECROSIS-FACTOR-ALPHA DECREASES IN-VIVO DIAPHRAGM CONTRACTILITYIN DOGS

In this study, we hypothesized that tumor necrosis factor a (TNF alpha ) is an important mediator of sepsis-related impairment in diaphragm c ontractility (1-2). In 12 anesthetized, ventilated dogs, bipolar stimu lating electrodes were placed on the phrenic nerves and diaphragm elec tromyographic activity (EMG) and shortening were recorded with needle electrodes and piezoelectric crystals, respectively. Transdiaphragmati c pressure (Pdi) was also recorded using esophageal (Pes) and abdomina l balloon catheters (Pdi = Pab - Pes). Dogs were randomized to receive saline injection (n = 6), or TNF alpha 60 mu g/kg (n = 6). All parame ters were recorded hourly for 6 h. Mean arterial blood pressure decrea sed 1 h after infusion in TNF alpha animals (p < 0.05) with no signifi cant change thereafter. Cardiac output increased early after TNF alpha infusion (p < 0.05) and remained at greater than baseline values at s tudy termination. Diaphragm pressure generation and costal shortening decreased progressively from 3 to 6 h post TNF alpha infusion (p < 0.0 5) with no significant change in control animals. Compound diaphragm a ction potential in response to supramaximal phrenic stimulation decrea sed in TNF alpha animals (p < 0.01) with no significant change in cont rol animals 3 and 6 h postinfusion. We conclude that TNF alpha infusio n was associated with significant declines in isotonic and quasi-isome tric diaphragm contraction and that this could be explained, at least in part, by impaired neuromuscular transmission.