| Mechanical ventilation (MV) engenders several clinical complications associated with the duration of MV. One consequence of MV is the difficulty to successfully wean a large portion of patients from the ventilator. In skeletal muscle, a reduced O2 supply results in contractile dysfunction and premature fatigue when performing external work. However, whether MV induces an O2 supply-usage imbalance in the diaphragm, which contributes to weaning difficulties, remains unknown. Here we demonstrate that MV induces a time-dependent reduction in diaphragm blood flow which results in a greatly diminished microvascular oxygenation. Furthermore, after as little as 6 hr of MV there is a severely compromised ability to increase blood flow within the diaphragm during contractions. Consistent with an O2 supply limitation, MV after 6 hr resulted in a ∼80 % reduction in O2 uptake during contractions compared to that achieved immediately after the onset of MV, which would force reliance on non-oxidative energy sources and hasten diaphragm fatigue. We also provide clear evidence for vascular dysfunction (i.e. Nitric Oxide (NO)-mediated, structural alterations) as a potential mechanism that contributes to the diminished diaphragm blood flow. These new and important findings reveal that prolonged MV results in a time-dependent decrease in the ability of the diaphragm to augment blood flow to match O2 demand in response to contractile activity. To our knowledge these are the first experiments that sought to determine the effects of mechanical ventilation on diaphragm oxygenation and vasomotor control. |
