Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Overview of the instrumentation for the Dark Energy Spectroscopic Instrument

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360–980 nm with a spectral resolution that ranges from 2000–5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii] doublet at 8 × 10−17 erg s−1 cm−2 in 1000 s for galaxies at z = 1.4–1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned

Noninvasive Point of Care Device for Assessing Cardiac Response to Acute Volume Changes

Purpose: The change in the amplitude of a peripheral pulse in response to a Valsalva maneuver has diagnostic utility for assessing volume status at the bedside. We have developed a device to automatically quantify the Valsalva pulse response (VPR) to a standardized Valsalva maneuver that the device guides a user to perform. In this study, we sought to determine whether VPR by the device, Indicor, is sensitive enough to detect the acute increase in central pressure and volume load that occurs with a passive leg raise (PLR) in healthy volunteers. Methods: Healthy volunteers were tested semirecumbently at 45 degrees, then again after being leaned back on a pivoted wedge with legs raised at 45 degrees and torso and head flat, and then again in the semirecumbent position. The device recorded a finger photoplethysmography (PPG) signal during a 10-second expiratory effort of 20 mmHg as guided by the device. VPR was automatically calculated as the ratio of the end-Valsalva pulse amplitude to the baseline pulse amplitude. Results: In the 30 participants who completed testing, VPR increased from baseline to PLR in every participant, from 0.34 ± 0.13 to 0.60 ± 0.14 (p \u3c 0.0001). Back upright, VPR decreased back to 0.33 ± 0.10 (p \u3c 0.0001 versus PLR; NS versus baseline position). Conclusion: In this proof-of-concept study of healthy participants, the Indicor device, a noninvasive, convenient device that automatically calculates VPR from a finger photoplethysmography signal during a standardized Valsalva maneuver, was sensitive enough to detect the increase in VPR that occurred with an acute central volume load from a PLR. Future studies should examine whether VPR responds differently to a PLR in heart failure patients with abnormal cardiac performance and/or congestion

Quantifying changes in size of arrhythmic photoplethysmography waveforms during a Valsalva maneuver for assessing cardiac filling pressure

OBJECTIVE: We previously showed that the change in amplitude of a finger photoplethysmography waveform during the Valsalva maneuver reflects cardiac filling pressure. However, the automated determination of peaks and valleys to calculate amplitude is limited in significant arrhythmias such as atrial fibrillation and premature ventricular complexes, which are common in heart failure. The purpose of this study was to assess the change in size of the waveform by calculating the change in root mean square (RMS) of the signal, thereby utilizing the entire cardiac cycle, and to compare it to change in size of peak-to-valley amplitude. APPROACH: We compared the two approaches in signals obtained from participants of a prior study who were tested prior to a clinically indicated cardiac catheterization. Correlation between the two methods was assessed in cases without, and then with, significant arrhythmias including atrial fibrillation or premature ventricular complexes. MAIN RESULTS: Calculations from the two methods of peak-valley amplitude and RMS were highly correlated with each other in signals without (0.99, p \u3c 0.0001, n = 252) and with significant arrhythmias (0.90, p \u3c 0.0001, n = 34). SIGNIFICANCE: RMS analysis of photoplethysmography signal size during the Valsalva maneuver is highly correlated with the method of analyzing changes in peak-valley amplitude, but does not rely on identifying peaks and valleys. The RMS method may be a more robust automated method of assessing cardiac filling pressure in patients with significant arrhythmias

The relationship between vascular wall shear stress and flow-mediated dilation: endothelial function assessed by phase-contrast magnetic resonance angiography

AbstractOBJECTIVESWe sought: 1) to investigate the relationship between vascular wall shear stress and flow-mediated dilation (FMD) in humans, and 2) to investigate whether this relationship could explain why FMD is greater in small arteries.BACKGROUNDArterial wall shear stress (WSS) is considered to be the primary stimulus for the endothelial-dependent FMD response. However, the relationship between WSS and FMD has not been investigated in humans. Furthermore, FMD is greater in small arteries, though the reasons for this phenomenon are unclear.METHODSUsing phase-contrast magnetic resonance angiography (PMRCA), we measured hyperemic WSS and FMD in 18 healthy volunteers. Peak systolic WSS was calculated assuming a blunted parabolic velocity profile. Diameter by PCMRA and by ultrasound was compared in nine subjects.RESULTSFlow-mediated dilation was linearly proportional to hyperemic peak systolic WSS (r = 0.79, p = 0.0001). Flow-mediated dilation was inversely related to baseline diameter (r = 0.62, p = 0.006), but the hyperemic peak WSS stimulus was also inversely related to baseline diameter (r = 0.47, p = 0.049). Phase-contrast magnetic resonance angiography and ultrasound diameters were compared in nine subjects and correlated well (r = 0.84, p < 0.0001), but diameter by PCMRA was greater (4.1 ± 0.7 mm vs. 3.7 ± 0.5 mm, p = 0.009).CONCLUSIONSArterial FMD is linearly proportional to peak hyperemic WSS in normal subjects. Thus, the endothelial response is linearly proportional to the stimulus. Furthermore, the greater FMD response in small arteries is accounted for, at least partially, by a greater hyperemic WSS stimulus in small arteries. By allowing the calculation of vascular WSS, which is the stimulus for FMD, and by imaging a fixed arterial cross-section, thus reducing operator dependence, PCMRA enhances the assessment of vascular endothelial function

A novel operator-independent noninvasive device for assessing arterial reactivity.

Background: Endothelial dysfunction is associated with increased risk of cardiovascular disease (CVD). Currently available noninvasive methods of measuring endothelial function have limitations. We tested a novel device that provides an automated measurement of the difference between baseline and post-ischemic, hyperemia-induced, brachial arterial compliance, a phenomenon known to be endothelium-dependent. The association between the calculated index, Flow-mediated Compliance Response (FCR), and established CVD risk indices was determined. Methods: Adults with CVD risk factors or known coronary artery disease (CAD) were enrolled. Framingham Risk Score (FRS) was calculated and presence of metabolic syndrome (MetSyn) was assessed. Carotid artery plaques were identified by ultrasound. Cardiorespiratory fitness was assessed by 6-minute walk test (6MWT). FCR was measured using the device. Results: Among 135 participants, mean age 49.3 +/- 17.9 years, characteristics included: 48% female, 7% smokers, 7% CAD, 10% type 2 diabetes, 34% MetSyn, and 38% with carotid plaque. Those with MetSyn had 24% lower FCR than those without (p \u3c 0.001). Lower FCR was associated with higher FRS percentile (r = -0.29, p \u3c 0.001), more MetSyn factors (r = -0.30, p \u3c 0.001), more carotid plaques (r = -0.22, p = 0.01), and lower 6MWT (r = 0.34, p \u3c 0.0001). Conclusion: FCR, an index of arterial reactivity obtained automatically using a novel, operator-independent device, was inversely associated with established CVD risk indices, increased number of carotid plaques, and lower cardiorespiratory fitness. Whether measuring FCR could play a role in screening for CVD risk and assessing whether endothelial function changes in response to treatments aimed at CVD risk reduction, warrants further study

Arterial Reactivity in Lower Extremities Is Progressively Reduced as Cardiovascular Risk Factors Increase Comparison With Upper Extremities Using Magnetic Resonance Imaging

ObjectivesOur goal was to investigate whether the association between established cardiovascular risk factors and arterial reactivity differs between the lower and upper extremities.BackgroundResistance artery reactivity in the arm is associated with cardiovascular risk factors, coronary disease, and events. However, the relationship of lower versus upper extremity vasoreactivity to increasing cardiovascular risk factors has not been determined.MethodsWe studied 82 subjects in 3 groups: 33 young healthy (YH) (21 to 41 years), 30 older healthy (OH) (>50 years), and 19 older type 2 diabetic subjects (OD). We directly measured systolic shear rate, flow, and radius in brachial and femoral arteries at rest and during post-occlusion hyperemia using magnetic resonance imaging.ResultsBrachial and femoral systolic shear rate, flow, and radius were similar among the groups at rest. Brachial hyperemic shear rate and hyperemic flow normalized as a function of baseline radius were not statistically different when YH were compared with OH and OH with OD. In contrast, femoral hyperemic shear rate and hyperemic flow normalized to baseline radius were lower in OH than YH (680 ± 236 s−1 vs. 843 ± 157 s−1, p = 0.001, and 0.84 ± 0.25 mm1.27/s vs. 1.01 ± 0.16 mm1.27/s, p = 0.001) and lower in OD than OH (549 ± 183 s−1, p = 0.02, and 0.74 ± 0.19 mm1.27/s, p = 0.046).ConclusionsPersons with increasing cardiovascular risk factor burden had progressively reduced arterial reactivity in lower but not upper extremities. This may help to explain why atherosclerosis usually develops more severely in legs than in arms, and suggests that legs may be more sensitive than arms for assessing early global atherosclerotic risk