Journal of applied physiology
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Cervical spinal cord injury (SCI) can dramatically impair diaphragm muscle function and often necessitates mechanical ventilation (MV) to maintain adequate pulmonary gas exchange. MV is a life-saving intervention. However, prolonged MV results in atrophy and impaired function of the diaphragm. ⋯ Our results demonstrate that compared with either condition alone, the combination of SCI and MV resulted in increased diaphragm atrophy, contractile dysfunction, and expression of atrophy-related genes, including MuRF1. Importantly, administration of the antioxidant Trolox attenuated proteolytic activation, fiber atrophy, and contractile dysfunction in the diaphragms of SCI + MV animals. These findings provide evidence that cervical SCI greatly exacerbates VIDD, but antioxidant therapy with Trolox can preserve diaphragm contractile function following acute SCI.
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The earliest description of what is now known as the acute respiratory distress syndrome (ARDS) was a highly lethal double pneumonia. Ashbaugh and colleagues (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE Lancet 2: 319-323, 1967) correctly identified the disease as ARDS in 1967. Their initial study showing the positive effect of mechanical ventilation with positive end-expiratory pressure (PEEP) on ARDS mortality was dampened when it was discovered that improperly used mechanical ventilation can cause a secondary ventilator-induced lung injury (VILI), thereby greatly exacerbating ARDS mortality. ⋯ The mechanical breath will be deconstructed to show that multiple parameters that comprise the breath-airway pressure, flows, volumes, and the duration during which they are applied to each breath-are critical to lung injury and protection. Specifically, the mechanisms by which a properly set mechanical breath can reduce the development of excessive fluid flux and pulmonary edema, which are a hallmark of ARDS pathology, are reviewed. Using our knowledge of how multiple parameters in the mechanical breath affect lung physiology, the optimal combination of pressures, volumes, flows, and durations that should offer maximum lung protection are postulated.
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Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. ⋯ In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans.
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Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. ⋯ Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.
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Review Meta Analysis
Clinical outcomes and cardiovascular responses to exercise training in heart failure patients with preserved ejection fraction: a systematic review and meta-analysis.
Exercise training induces physical adaptations for heart failure patients with systolic dysfunction, but less is known about those patients with preserved ejection fraction. To establish whether exercise training produces changes in peak V̇o2 and related measures, quality of life, general health, and diastolic function in heart failure patients with preserved ejection fraction. We conducted a MEDLINE search (1985 to October 10, 2014), for exercise-based rehabilitation trials in heart failure, using search terms "exercise training, heart failure with preserved ejection fraction, heart failure with normal ejection fraction, peak V̇o₂, and diastolic heart dysfunction". ⋯ The corresponding data are provided for the following exercise test variables: V̇e/V̇co₂ slope, MD 0.85 ml·kg(-1)·min(-1) (95% CI 0.05 to 1.65, P = 0.04); maximum heart rate, MD 5.60 beats per minute (95% CI 3.95 to 7.25, P < 0.00001); Six-Minute Walk Test, MD 32.1 m (95% CI 17.2 to 47.1, P < 0.0001); and indices of diastolic function: E/A ratio, MD 0.07 (95% CI 0.02 to 0.12, P = 0.005); E/E' ratio MD -2.31 (95% CI -3.44 to -1.19, P < 0.0001); deceleration time (DT), MD -13.2 ms (95% CI -19.8 to -6.5, P = 0.0001); and quality of life: Minnesota Living with Heart Failure Questionnaire, MD -6.50 (95% CI -9.47 to -3.53, P < 0.0001); and short form-36 health survey (physical dimension), MD 15.6 (95% CI 7.4 to 23.8, P = 0.0002). In 3,744 h patient-hours of training, not one death was directly attributable to exercise. Exercise training appears to effect several health-related improvements in people with heart failure and preserved ejection fraction.