Journal of applied physiology
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The frequency-response of pressure autoregulation is not well delineated; therefore, the optimal frequency of arterial blood pressure (ABP) modulation for measuring autoregulation is unknown. We hypothesized that cerebrovascular autoregulation is band-limited and delineated by a cutoff frequency for which ABP variations induce cerebrovascular reactivity. Neonatal swine (n = 8) were anesthetized using constant minute ventilation while positive end-expiratory pressure (PEEP) was modulated between 6 and 0.75 cycles/min (min(-1)). ⋯ Data taken above LLA fit a Butterworth high-pass filter model with a cutoff frequency at 1.8 min(-1) (95% confidence interval: 1.5-2.2). Cerebrovascular reactivity occurs for sustained ABP changes lasting 30 s or longer. The ability to distinguish intact and impaired autoregulation was maximized by a 60-s wave (1 min(-1)), which was 100% sensitive and 100% specific in this model.
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Recently, several high-impact reviews suggest that regular aerobic exercise is beneficial for maintaining cognitive function in aging adults. Higher cerebral blood flow and/or cerebrovascular reactivity may explain the favorable effect of exercise on cognition. In addition, prostaglandin-mediated vasodilator responses may be influenced by regular exercise. ⋯ Furthermore, the change in MCAv reactivity (between baseline and indomethacin trials) was also associated with Vo2max (r = 0.59; P < 0.05) in older adults. Cerebral vasodilator responses to hypercapnia were associated with maximal aerobic capacity in healthy older adults. These results may explain the physiological link between regular aerobic exercise and improved cognitive function in aging adults.
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Prolonged skeletal muscle inactivity results in a rapid decrease in fiber size, primarily due to accelerated proteolysis. Although several proteases are known to contribute to disuse muscle atrophy, the ubiquitin proteasome system is often considered the most important proteolytic system during many conditions that promote muscle wasting. Emerging evidence suggests that calpain and caspase-3 may also play key roles in inactivity-induced atrophy of respiratory muscles, but it remains unknown if these proteases are essential for disuse atrophy in limb skeletal muscles. ⋯ Independent pharmacological inhibition of calpain or caspase-3 prevented this casting-induced atrophy. Interestingly, inhibition of calpain activity also prevented caspase-3 activation, and, conversely, inhibition of caspase-3 prevented calpain activation. These findings indicate that a regulatory cross talk exists between these proteases and provide the first evidence that the activation of calpain and caspase-3 is required for inactivity-induced limb muscle atrophy.
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A profound remodeling of the diaphragm and vastus lateralis (VL) occurs in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In this mini-review, we discuss the following costal diaphragm remodeling features noted in patients with moderate-to-severe COPD: 1) deletion of serial sarcomeres, 2) increased proportion of slow-twitch fibers, 3) fast-to-slow isoform shift in sarco(endo)plasmic reticulum Ca(2+)-ATPase, 4) increased capacity of oxidative metabolism, 5) oxidative stress, and 6) myofiber atrophy. ⋯ For each of the remodeling features noted in both the VL and costal diaphragm of COPD patients, we present mechanisms that are currently thought to mediate these changes as well as the pathophysiology of each remodeling feature. We hope that our mechanistic presentation stimulates research in this area that focuses on improving the ability of COPD patients to carry out increased activities of daily living.