An experimental study was performed to determine the main site of fatigue associated with diaphragm pacing. Using 24 mature mongrel dogs, weighing 7.5 to 12.7 kg, direct phrenic nerve pacing was conducted from the right cervical area at three different respiration rates, 37 (Group 1, n = 6), 25 (Group 2, n = 6) and 12 (Group 3, n = 6) times per minute, under fixed stimulation conditions (pulse duration, 200 μsec; frequency, 25 Hz; pulse train repetition time, 1.2 sec). Diaphragm fatigue was defined as the reduction in transdiaphragmatic pressure (Pdi) to less than or equal to 60% of the initial value. In each animal, tidal volume (Vt), induced muscle action potential (Edi), conduction time (CT) and electrical current (E) between two electrodes were examined at various periods until fatigue. In addition, after fatigue, aminophylline (10 mg/kg) was injected and each parameter was observed for an additional 45 min. In 10 animals, the polarity of stimulation was changed from anodal to cathodal current after fatigue and changes in Pdi and Edi were examined. The time to fatigue was 70 ± 20 min for Group 1, 149 ± 48 min for Group 2, and 371 ± 97 min for Group 3, showing a significant stimulation rate dependency (P < 0.05). Vt and Edi showed a significant decrease (P < 0.05) at fatigue in all of the groups. However, no significant differences of CT and E were seen between pre- and postfatigue values. Pdi and Edi did not change even when polarity was changed after fatigue. Following administration of aminophylline, Pdi showed a significant (P < 0.05) increase over time in all groups: 19.8 ± 13.5% at 5 min, 23.0 ± 13.5% at 15 min, and 16.2 ± 14.9% at 30 min for Group 1: 23.6 ± 11.6% at 5 min, 27.3 ± 15.5% at 15 min, and 19.0 ± 16.1% at 30 min for Group 2; and 29.9 ± 21.1% at 5 min, 29.5 ± 18.6% at 15 min, 22.3 ± 13.8% at 30 min, and 15.5 ± 13.4% at 45 min for Group 3. In contrast, administration of aminophylline caused no significant changes in Edi. Based upon the finding that aminophylline was significantly effective at the time of diaphragm fatigue, it is concluded that fatigue of the muscle itself constitutes one of the contributing factors for the fatigue phenomenon associated with diaphragm pacing.
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