Reversibility of Diaphragm Fatigue by Mechanical Hyperperfusion

Abstract Diaphragm function is thought to depend on the balance between diaphragm blood flow and metabolic demand. If blood flow is inadequate, fatigue should ensue. Likewise, in the presence of fatigue, function should improve when blood flow is increased. To test this hypothesis, we evaluated the effect of increasing blood flow to the fatigued diaphragm. Studies were performed on anesthetized, mechanically ventilated dogs in which strips of costal diaphragm were developed in situ. Strip tension was measured with an isometric tension transducer. The inferior phrenic artery supplying the strip was cannulated and pump perfused at a pressure of 92 ± 3 mm Hg; phrenic artery flow and pressure were continuously monitored with in-line doppler flow probes and pressure transducers, respectively. Fatigue was produced by electrically stimulating strips to contract 15 times/min (initial tension 80% of maximum, duty cycle 50%). Rhythmic contraction resulted in a downward shift in the diaphragm force-frequency relationship in all strips. In eight strips, stepwise increments in phrenic artery perfusion pressure to 161 ± 8 and 281 ± 17 mm Hg were produced by increasing pump speed at 6 and 8 min into rhythmic stimulation; in four strips, phrenic artery perfusion pressure was increased to 152 ± 20 and 257 ± 32 mm Hg at 20 and 25 mm into rhythmic stimulation, respectively. Each increase in phrenic artery pressure resulted in increases in phrenic artery flow and diaphragm tension and produced an upshift in the diaphragm force-frequency relationship. For example, the tensions developed by eight strips at low (10 Hz) and high (50 Hz) stimulation frequencies increased by 19 ± 7 and 31 ± 9%, respectively, with the first increase in pump speed, and increased by an additional 22 ± 5 and 25 ± 5%, respectively, following a second increase in pump speed at 8 min into rhythmic contraction. Similar upshifts in the force-frequency relationship were observed in the four strips in which pump speed was increased at 20 and 25 min into contraction. We conclude that diaphragm fatigue can be partially reversed by increasing phrenic blood flow. The effects of hyperperfusion on contractility were neither qualitatively nor quantitatively different after prolonged, as compared to shorter, periods of rhythmic contraction.