Tumor necrosis factor alpha decreases in vivo diaphragm contractility in dogs.
In this study, we hypothesized that tumor necrosis factor alpha (TNF alpha) 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 TNF alpha 60 micrograms/kg (n = 6). All parameters were recorded hourly for 6 h. Mean arterial blood pressure decreased 1 h after infusion in TNF alpha animals (p < 0.05) with no significant change thereafter. Cardiac output increased early after TNF alpha 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 TNF alpha infusion (p < 0.05) with no significant change in control animals. Compound diaphragm action potential in response to supramaximal phrenic stimulation decreased in TNF alpha animals (p < 0.01) with no significant change in control animals 3 and 6 h postinfusion. We conclude that TNF alpha 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.
Department of Medicine, University Hospital (UBC), Vancouver, Canada.
P G
PG
Wilcox
Y
Y
Wakai
K R
KR
Walley
D J
DJ
Cooper
J
J
Road
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D009119:Muscle Contraction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha