Ryan Rosenberry

Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy

Dystrophin deficiency disrupts sarcolemmal targeting of neuronal nitric oxide synathase, resulting in functional muscle ischaemia. Chronic treatment of dystrophic mice with an inorganic nitric oxide (NO) donor alleviates this ischaemia and improves many features of the dystrophic phenotype. The present study translates this preclinical work by showing that a single oral dose of sodium nitrate,which serves as a NO donor when reduced to circulating nitrite by the commensal bacteria in the oral cavity, alleviates functional muscle ischaemia and restores normal blood flow regulation in human patients with dystrophinopathy. The results of the present study further support the mechanistic hypothesis that circulating nitrite serves as an alternative NO donor when reduced by deoxyhaemoglobin and/or deoxymyoglobin in exercising muscle.

Age‐related microvascular dysfunction: novel insight from near‐infrared spectroscopy

What is the central question of this study? Can near‐infrared spectroscopy (NIRS)‐derived post‐occlusion tissue oxygen saturation recovery kinetics be used to study age‐related impairments in microvascular function? What is the main finding and its importance? Using a previously established 5 min cuff occlusion protocol, we found that NIRS‐derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.

Near‐infrared spectroscopy detects age‐related differences in skeletal muscle oxidative function: promising implications for geroscience

Age is the greatest risk factor for chronic disease and is associated with a marked decline in functional capacity and quality of life. A key factor contributing to loss of function in older adults is the decline in skeletal muscle function. While the exact mechanism(s) remains incompletely understood, age‐related mitochondrial dysfunction is thought to play a major role. To explore this question further, we studied 15 independently living seniors (age: 72 ± 5 years; m/f: 4/11; BMI: 27.6 ± 5.9) and 17 young volunteers (age: 25 ± 4 years; m/f: 8/9; BMI: 24.0 ± 3.3). Skeletal muscle oxidative function was measured in forearm muscle from the recovery kinetics of muscle oxygen consumption using near‐infrared spectroscopy (NIRS). Muscle oxygen consumption was calculated as the slope of change in hemoglobin saturation during a series of rapid, supra‐systolic arterial cuff occlusions following a brief bout of exercise. Aging was associated with a significant prolongation of the time constant of oxidative recovery following exercise (51.8 ± 5.4 sec vs. 37.1 ± 2.1 sec, P = 0.04, old vs. young, respectively). This finding suggests an overall reduction in mitochondrial function with age in nonlocomotor skeletal muscle. That these data were obtained using NIRS holds great promise in gerontology for quantitative assessment of skeletal muscle oxidative function at the bed side or clinic.

Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with 'One Stop Shop' Near-infrared Spectroscopy

Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic demand. Reactive hyperemia (in response to a brief period of tissue ischemia) is an independent predictor of cardiovascular events and provides important insight into vascular health and vasodilatory capacity. Skeletal muscle oxidative capacity is equally important in health and disease, as it determines the energy supply for myocellular processes. Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess each of these major clinical endpoints (reactive hyperemia, neurovascular coupling, and muscle oxidative capacity) during a single clinic or laboratory visit. Unlike Doppler ultrasound, magnetic resonance images/spectroscopy, or invasive catheter-based flow measurements or muscle biopsies, our approach is less operator-dependent, low-cost, and completely non-invasive. Representative data from our lab taken together with summary data from previously published literature illustrate the utility of each of these end-points. Once this technique is mastered, application to clinical populations will provide important mechanistic insight into exercise intolerance and cardiovascular dysfunction.

Concurrent measurement of skeletal muscle blood flow during exercise with diffuse correlation spectroscopy and Doppler ultrasound

Noninvasive, direct measurement of local muscle blood flow in humans remains limited. Diffuse correlation spectroscopy (DCS) is an emerging technique to measure regional blood flow at the microvascular level. In order to better understand the strengths and limitations of this novel technique, we performed a validation study by comparing muscle blood flow changes measured with DCS and Doppler ultrasound during exercise. Nine subjects were measured (all males, 27.4 ± 2.9 years of age) for a rhythmic handgrip exercise at 20% and 50% of individual maximum voluntary contraction (MVC), followed by a post-exercise recovery. The results from DCS and Doppler ultrasound were highly correlated (R = 0.99 ± 0.02). DCS was more reliable and less susceptible to motion artifact.