Diaphragmatic fatigue after endotoxemic shock in rats: in vitro function and metabolism

A rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time-dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores.