Abstract
To study the effect of human recombinant tumour necrosis factor alpha (TNF alpha) on contracture development and changes in the ionic composition of the external bathing solution of electrically stimulated rat hemidiaphragm preparations in vitro. A triphasic controlled in vitro study using isolated tissue preparations treated in one of four ways. Phase 1 was a control period for all groups; in phase 2 preparations were exposed to TNF, TNF in calcium-free solution, TNF in magnesium-substituted calcium-free solution or no treatment (control); in phase 3 halothane was added to all preparations. The effect of anti-TNF antibody on contracture responses to TNF was studied in separate experiments. Laboratories of the Academic Unit of Anaesthesia, University of Leeds, UK. Changes in baseline tension and concentrations of potassium and sodium ions in the external bathing medium were measured for each group in each phase. In addition, changes in calcium ion concentration in the external bathing medium were measured for the control and TNF (in calcium-containing solution) groups in each phase. TNF, either in standard Krebs' solutions (p = 0.039) or calcium-free Krebs' solution (p = 0.014), produced an increased incidence of contracture development compared to control, whereas TNF in magnesium-substituted calcium-free Krebs' solution did not. In all three TNF groups there were significant increases in sodium and potassium ion concentrations compared to control, but the changes were significantly fewer in the magnesium-substituted calcium-free group than the two other TNF groups. There was a significant fall in calcium ion concentration in the TNF group compared to control. Anti-TNF antibody reduced the contracture response to halothane in the presence of TNF (p < 0.05). The results support the hypothesis that TNF acts to increase release of calcium from intracellular stores that are subject to modulation by influx of extracellular calcium or membrane depolarisation.
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