Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P \u3c 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P \u3c 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P \u3c 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P \u3c 0.05), which was related to exercise tolerance of the patients (r = 0.64, P \u3c 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease

Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P \u3e 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P \u3c 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P \u3c 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to β-actin, P \u3c 0.05). Furthermore, CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P \u3c 0.05), but not PA (P \u3e 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself

Elastic optical interface with variable baudrate: Architecture and proof-of-concept

Varying the symbol rate is an alternative or complementary approach to varying the modulation format or the channel spacing to turn optical networks into elastic networks. We propose to allocate just-enough bandwidth for each optical connection by adjusting the symbol rate such that the penalty originating from long cascades of optical filters is contained. This helps reduce overprovisioning for lightpaths where full capacity is not needed, by (i) eliminating unnecessary regenerators and (ii) reducing the power consumption of terminals, when the clock rate of electronics is reduced along with the baudrate. We propose a novel architecture for an elastic optical interface by combining a variable bitrate transceiver, paired with an elastic aggregation stage, with software-defined control. We then report a real-Time field-programmable-gate-Array-based prototype that delivers flexible transport frames to be sent with a polarization-division multiplexed quadrature phase-shift keying modulation format. We interconnect this prototype with a commercial optical transport network switch and a centralized controller. We demonstrate fast and hitless reconfiguration of the interface and measure the reconfiguration time of hardware logic ( < 450 μs), as well as end-To-end control and the data plane ( < 0.9 s)

Acute high-intensity exercise and skeletal muscle mitochondrial respiratory function: role of metabolic perturbation

Recently it was documented that fatiguing, high-intensity exercise resulted in a significant attenuation in maximal skeletal muscle mitochondrial respiratory capacity, potentially due to the intramuscular metabolic perturbation elicited by such intense exercise. With the utilization of intrathecal fentanyl to attenuate afferent feedback from group III/IV muscle afferents, permitting increased muscle activation and greater intramuscular metabolic disturbance, this study aimed to better elucidate the role of metabolic perturbation on mitochondrial respiratory function. Eight young, healthy males performed high-intensity cycle exercise in control (CTRL) and fentanyl-treated (FENT) conditions. Liquid chromatography-mass spectrometry and high-resolution respirometry were used to assess metabolites and mitochondrial respiratory function, respectively, pre- and postexercise in muscle biopsies from the vastus lateralis. Compared with CTRL, FENT yielded a significantly greater exercise-induced metabolic perturbation (PCr: −67% vs. −82%, Pi: 353% vs. 534%, pH: −0.22 vs. −0.31, lactate: 820% vs. 1,160%). Somewhat surprisingly, despite this greater metabolic perturbation in FENT compared with CTRL, with the only exception of respiratory control ratio (RCR) (−3% and −36%) for which the impact of FENT was significantly greater, the degree of attenuated mitochondrial respiratory capacity postexercise was not different between CTRL and FENT, respectively, as assessed by maximal respiratory flux through complex I (−15% and −33%), complex II (−36% and −23%), complex I + II (−31% and −20%), and state 3CI+CII control ratio (−24% and −39%). Although a basement effect cannot be ruled out, this failure of an augmented metabolic perturbation to extensively further attenuate mitochondrial function questions the direct role of high-intensity exercise-induced metabolite accumulation in this postexercise response

Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 \ub1 1 mmHg), whereas both HR and CO increased from baseline (6.0 \ub1 1.1 beats/min, and 0.8 \ub1 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 \ub1 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 \ub1 189 ml/min; 11.9 \ub1 1.5 ml\ub7min-1\ub7mmHg-1, respectively) and sPLM (878 \ub1 119 ml/min; 10.9 \ub1 1.6 ml\ub7min-1\ub7mmHg-1, respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically. NEW & NOTEWORTHY: Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more useful clinically

Skeletal muscle ATP synthesis and cellular H+ handling measured by localized 31P-MRS during exercise and recovery

31P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H+) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60–75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP-model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism

First demonstration of multi-vendor and multi-domain EON with S-BVT and control interoperability over Pan-European testbed

The operation of multi-domain and multi-vendor EONs can be achieved by interoperable Sliceable Bandwidth Variable Transponders, a GMPLS / BGP-LS-based control plane and a planning tool. This paper reports the first full demonstration and validation this end-to-end architecture

Life-threatening hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy: report of a case

<p>Abstract</p> <p>Background</p> <p>Hemobilia is a rare but lethal biliary tract complication. There are several causes of hemobilia which might be classified as traumatic or nontraumatic. Hemobilia caused by pseudoaneurysm might result from hepatobiliary surgery or percutaneous interventional hepatobiliary procedures. However, to our knowledge, there are no previous reports pertaining to hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy.</p> <p>Case presentation</p> <p>A 65-year-old male was admitted to our hospital because of acute calculous cholecystitis and cholangitis. He underwent cholecystectomy, choledocholithotomy via a right upper quadrant laparotomy and a temporary T-tube choledochostomy was created. However, on the 19th day after operation, he suffered from sudden onset of hematemesis and massive fresh blood drainage from the T-tube choledochostomy. Imaging studies confirmed the diagnosis of pseudoaneurysm associated hemobilia. The probable association of T-tube choledochostomy with pseudoaneurysm and hemobilia is also demonstrated. He underwent emergent selective microcoils emobolization to occlude the feeding artery of the pseudoaneurysm.</p> <p>Conclusions</p> <p>Pseudoaneurysm associated hemobilia may occur after T-tube choledochostomy. This case also highlights the importance that hemobilia should be highly suspected in a patient presenting with jaundice, right upper quadrant abdominal pain and upper gastrointestinal bleeding after liver or biliary surgery.</p

Severe loss of mechanical efficiency in COVID‐19 patients

Background: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). Methods: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2 peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. Results: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2 peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2 , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2 peak and DE and between the peak power output and DE (P < 0.001). Conclusions: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation