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Fatigue and rest of the hamster diaphragm Reid, Wendy Darlene


Decreased respiratory muscle strength and/or excessive loads imposed on the respiratory muscles by disease may result in respiratory muscle fatigue and ventilatory failure. Once the respiratory muscles fatigue, the only treatment is rest by mechanical ventilation. However, no one has yet determined the best protocol of rest. The purpose of these studies was to develop an animal model in the hamster in order to examine the time course of recovery following fatigue of the diaphragm and specifically, to test whether mechanical ventilation or spontaneous unloaded breathing was a better mode for functional recovery. The studies required the initial development of an anesthetic regimen which produced minimal respiratory depression in the hamster. A new method of stimulating the diaphragm in small animals was developed by apposing plate electrodes directly against the diaphragm. The validity of this technique was examined and comparison of the mechanical and electrophysiological response to that of phrenic nerve stimulation were similar at maximal stimulation. The histological characteristics of the normal hamster diaphragm were determined for fibre type proportions and sizes, oxidative capacity and glycogen levels in the costal and crural regions of this muscle. The examination revealed three distinct areas of the diaphragm with different histological features: the abdominal surface of the crural region, the thoracic surface of the crural region and the sternal and costal region. Diaphragmatic fatigue was induced in vivo by repetitive electrical stimulation which resulted in both high and low frequency fatigue. The fatigue stimulus also produced muscle fibre damage, primarily along the abdominal surface of the diaphragm over the electrodes, and glycogen depletion in the type lib fibres. Rest by continuous mechanical ventilation resulted in recovery of high frequency fatigue in the hamster diaphragm whereas rest by spontaneous unloaded breathing resulted in no recovery. Sham fatigue groups rested by either mechanical ventilation or spontaneous breathing demonstrated progressive deterioration in transdiaphragmatic pressure throughout the rest period. Decreased muscle fibre damage but increased inflammation and glycogen depletion was demonstrated in all four fatigue/sham fatigue and rest groups compared to that demonstrated by the fatigue/sham fatigue only groups. The results suggest that passive rest by continuous mechanical ventilation promotes recovery following fatigue induced by electrical stimulation. Additional factors such as prolonged fasting, loads imposed on the diaphragm by the plate electrode apparatus, positive pressure ventilation, and cumulative effects of intraperitoneal urethane likely contributed to the progressive deterioration of diaphragmatic function demonstrated in the animals of the two sham groups rested by either spontaneous breathing or mechanical ventilation, and confounded the results shown by the two fatigue groups rested by either spontaneous breathing or mechanical ventilation.

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