EFFECTS OF ENDOTOXIC-SHOCK ON DIAPHRAGMATIC FUNCTION IN MECHANICALLY VENTILATED RATS

Diaphragmatic function was investigated in mechanically ventilated rats during endotoxic shock (group E, n = 18) and after saline solution injection (group C, n = 8). Endotoxic shock was produced by a 1-min injection of Escherichia coli endotoxin (10 mg/kg iv) suspended in saline. Diaphragmatic strength was assessed before (T0) and 15 (T15) and 60 (T60) min after injection by measuring transdiaphragmatic pressure (Pdi) generated during bilateral phrenic stimulation at 0.5, 10, 20, 30, 50, and 100 Hz. Diaphragmatic neuromuscular transmission was assessed by measuring the integrated electrical activity of the diaphragm. Diaphragmatic endurance was assessed 75 min after injection from the rate of Pdi decline after a 30-s continuous 10-Hz phrenic stimulation. In 16 additional animals, diaphragmatic glycogen content was determined 60 min after inoculation with endotoxin (n = 8) or 0.9% sodium chloride solution (n = 8). Diaphragmatic resting membrane potential (E(m)) was measured in 16 additional animals 60 min after endotoxin (n = 8) or saline injection (n = 8). Mean blood pressure decreased from 74 +/- 3 to 53 +/- 6 mmHg at T60 in group E, whereas it was maintained in group C. At T60 Pdi was decreased in group E for frequencies of 50 and 100 Hz and was associated with a decreased diaphragmatic electromyographic activity of 25.3 +/- 2.5 and 26.5 +/- 5.2% for 50- and 100-Hz stimulations, respectively, in comparison with T0 values. No change was observed in group C. At the end of the endurance test, Pdi amounted to 75.6 +/- 2.9% of the initial value in group E, whereas it remained unchanged in group C(P < 0.01). Sixty minutes after endotoxin inoculation, diaphragmatic glycogen concentration was 40.2 +/-3.5 and 27.7 +/- 2.4 mg/g protein content in groups C and E, respectively (P < 0.01). E(m) decreased from -91.8 +/- 3 to -78.2 +/- 5.9 mV 60 min after endotoxin injection, whereas no change was observed after saline administration (P < 0.01). In conclusion, during endotoxic shock, diaphragmatic dysfunction in mechanically ventilated animals is mainly related to an impaired neuromuscular transmission secondary to a decreased E(m).