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

Progress update and challenges on VO2max testing and interpretation

The maximal oxygen uptake (VO2max) is the primary determinant of endurance performance in heterogeneous populations and has predictive value for clinical outcomes and all-cause mortality. Accurate and precise measurement of VO2max requires the adherence to quality control procedures, including combustion testing and the use of standardized incremental exercise protocols with a verification phase preceded by an adequate familiarization. The data averaging strategy employed to calculate the VO2max from the breath-by-breath data can change the VO2max value by 4-10%. The lower the number of breaths or smaller the number of seconds included in the averaging block, the higher the calculated VO2max value with this effect being more prominent in untrained subjects. Smaller averaging strategies in number of breaths or seconds (less than 30 breaths or seconds) facilitate the identification of the plateau phenomenon without reducing the reliability of the measurements. When employing metabolic carts, averaging intervals including 15 to 20 breaths or seconds are preferable as a compromise between capturing the true VO2max and identifying the plateau. In training studies, clinical interventions and meta-analysis, reporting of VO2max in absolute values and inclusion of protocols and the averaging strategies arise as imperative to permit adequate comparisons. Newly developed correction equations can be used to normalize VO2max to similar averaging strategies. A lack of improvement of VO2max with training does not mean that the training program has elicited no adaptations, since peak cardiac output and mitochondrial oxidative capacity may be increased without changes in VO2max

Greater Reduction in Abdominal Than in Upper Arms Subcutaneous Fat in 10- to 12-Year-Old Tennis Players: A Volumetric MRI Study

Background: Little is known about the impact of long term participation in sports and subcutaneous fat volume in children. This study aimed at determining whether tennis participation is associated with lower subcutaneous adipose tissue volume (SATv) in the abdominal and upper extremities in children. Methods: Magnetic resonance imaging (MRI) was used to determine the SATv stored in the abdominal region and upper arms in seven tennis players and seven inactive children matched by height and age (147 cm and 10.9 years). All participants were in Tanner stage 1 or 2. Results: Playing tennis was associated with 48% (P = 0.001) lower abdominal SATv and 17–18% (P > 0.05) lower upper arms SATv compared to controls. The ratio between abdominal/upper arms SATv was larger in the controls vs. tennis players (69% P = 0.001). The SATv was similar in the dominant and non-dominant arm within each group. Conclusion: Playing tennis during childhood is associated with reduced SATv in the abdominal region and a more favorable regional distribution of fat. Despite the large amount of contractile activity of the playing (dominant) arm, there was no indication of between-arms differences in SATv

Contribution of oxygen extraction fraction to maximal oxygen uptake in healthy young men

We analysed the importance of systemic and peripheral arteriovenous O2 difference (a-vO2 difference and a-vfO2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake (VO2max). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with VO2max. Articles (n=17) publishing individual data (n=154) on VO2max, maximal cardiac output (Qmax; indicator-dilution or the Fick method), a-vO2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n=27; subjects: n=234) on leg blood flow (LBF; thermodilution), a-vfO2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Qmax and two-LBF increased linearly by 4.9-6.0 L · min–1 per 1 L · min–1 increase in VO2max (R2=.73 and R2=.67, respectively; both P<.001). The a-vO2 difference increased from 118-168mL · L–1 from a VO2max of 2-4.5 L · min–1 followed by a reduction (second-order polynomial: R2=.27). After accounting for a hypoxemia-induced de-crease in arterial O2 content with increasing VO2max (R2=.17; P<.001), systemic O2 extraction fraction increased up to ~90% (VO2max: 4.5 L · min–1) with no further change (exponential decay model: R2=.42). Likewise, leg O2 extraction fraction increased with VO2max to approach a maximal value of ~90-95% (R2=.83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with VO2max (R2=.77 and R2=.31, respectively; both P<.01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to VO2max, enhanced O2 extraction fraction (90%) contributes to the remarkably high VO2max in endurance-trained individuals

An integrative approach to the regulation of mitochondrial respiration during exercise: Focus on high-intensity exercise

During exercise, muscle ATP demand increases with intensity, and at the highest power output, ATP consumption may increase more than 100-fold above the resting level. The rate of mitochondrial ATP production during exercise depends on the availability of O2, carbon substrates, reducing equivalents, ADP, Pi, free creatine, and Ca2+. It may also be modulated by acidosis, nitric oxide and reactive oxygen and nitrogen species (RONS). During fatiguing and repeated sprint exercise, RONS production may cause oxidative stress and damage to cellular structures and may reduce mitochondrial efficiency. Human studies indicate that the relatively low mitochondrial respiratory rates observed during sprint exercise are not due to lack of O2, or insufficient provision of Ca2+, reduced equivalents or carbon substrates, being a suboptimal stimulation by ADP the most plausible explanation. Recent in vitro studies with isolated skeletal muscle mitochondria, studied in conditions mimicking different exercise intensities, indicate that ROS production during aerobic exercise amounts to 1-2 orders of magnitude lower than previously thought. In this review, we will focus on the mechanisms regulating mitochondrial respiration, particularly during high-intensity exercise. We will analyze the factors that limit mitochondrial respiration and those that determine mitochondrial efficiency during exercise. Lastly, the differences in mitochondrial respiration between men and women will be addressed

Advantages of in vivo measurement of human skin thermal conductance using a calorimetric sensor

Thermal conductivity of the skin has been measured by in vivo procedures since the 1950s. These devices usually consist of temperature sensors and heating elements. In vivo measurement of skin thermal conductivity entails several difficulties. It is necessary to adequately characterize the excitation produced by the measurement. In addition, the thermal penetration depth of each instrument is different. These factors have led to the development of a multitude of techniques to measure the thermal conductivity or related magnitudes such as thermal conductance. In our case, we have built a calorimetric sensor designed to measure this magnitude directly and non-invasively. The device implements the basic principles of calorimetry and is capable of characterizing the thermal magnitudes of a 2 × 2 (4) cm2 skin region. The sensor consists of a measuring thermopile with a thermostat cooled by Peltier effect. Several skin measurements performed under different conditions resulted in a thermal conductance ranging from 0.017 to 0.050 WK−1. This magnitude, measured in vivo, is different in each studied area and depends on several factors, such as physical activity and the physiological state of the subject. This new sensor is a useful tool for studying the human body thermoregulatory response

Heat flow, heat capacity and thermal resistance of localized surfaces of the human body using a new calorimetric sensor

A non-invasive sensor equipped with a programmable thermostat has been developed to assess in vivo the heat flow transmitted by conduction from human skin to the sensor thermostat. This device enables the assessment of the thermal properties of a 2 × 2 cm2 skin surface with a thermal penetration depth of 3–4 mm. In this work, we report the thermal magnitudes recorded with this sensor in 6 different areas (temple, hand, abdomen, thigh, wrist and heel) of 6 healthy subjects of different genders and ages, which were measured under resting conditions. Heat flow and equivalent thermal resistance are proportionally related to each other and are highly variable in magnitude and different for each zone. The heat capacity is also different for each zone. The heat flow values varied from 362 ± 17 mW at the temple to 36 ± 12 mW at the heel for the same subject, when the sensor thermostat was set at 26 °C. The equivalent thermal resistance ranged from 23 ± 2 K W−1 in the volar area of the wrist to 52 ± 4 KW−1 in the inner thigh area. The heat capacity varies from 4.8 ± 0.4 J K−1 in the heel to 6.4 ± 0.2 J K−1 in the abdomen. These magnitudes were also assessed over a 2 × 1 cm2 second-degree burn scar in the volar area of the wrist. The scar area had 27.6 and 11.6% lower heat capacity and equivalent thermal resistance, respectively, allowing an increased heat flow in the injured area. This work is a preliminary study of the measurement capacity of this new instrument

Impact of data averaging strategies on V̇O2max assessment: Mathematical modeling and reliability

Background: No consensus exists on how to average data to optimize VO2max assessment. Although the VO2max value is reduced with larger averaging blocks, no mathematical procedure is available to account for the effect of the length of the averaging block on VO2max. Aims: To determine the effect that the number of breaths or seconds included in the averaging block has on the VO2max value and its reproducibility and to develop correction equations to standardize VO2max values obtained with different averaging strategies. Methods: Eighty‐four subjects performed duplicate incremental tests to exhaustion (IE) in the cycle ergometer and/or treadmill using two metabolic carts (Vyntus and Vmax N29). Rolling breath averages and fixed time averages were calculated from breath‐by‐breath data from 6 to 60 breaths or seconds. Results: VO2max decayed from 6 to 60 breath averages by 10% in low fit (VO2max 0.97). There was a linear‐log relationship between the number of breaths or seconds in the averaging block and VO2max (R2 > 0.99, P < 0.001), and specific equations were developed to standardize VO2max values to a fixed number of breaths or seconds. Reproducibility was higher in trained than low‐fit subjects and not influenced by the averaging strategy, exercise mode, maximal respiratory rate, or IE protocol. Conclusions: The VO2max decreases following a linear‐log function with the number of breaths or seconds included in the averaging block and can be corrected with specific equations as those developed here

Treatment of hypertension with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and resting metabolic rate: A cross-sectional study

Hypertension in obese and overweight patients is associated with an elevated resting metabolic rate (RMR). The aim of this study was to determine whether RMR is reduced in hypertensive patients treated with angiotensin-converting enzyme inhibitors (ACEI) and blockers (ARB). The RMR was determined by indirect calorimetry in 174 volunteers; 93 (46.5 %) were hypertensive, of which 16 men and 13 women were treated with ACEI/ARB, while 30 men and 19 women with untreated hypertension served as a control group. Treated and untreated hypertensives had similar age, BMI, physical activity, and cardiorespiratory fitness. The RMR normalized to the lean body mass (LBM) was 15% higher in the untreated than ACEI/ARB-treated hypertensive women (p = .003). After accounting for LBM, whole-body fat mass, age, the double product (heart rate x systolic blood pressure), and the distance walked per day, the RMR was 2.9% lower in the patients taking ACEI/ARB (p = .26, treatment x sex interaction p = .005). LBM, age, and the double product explained 78% of the variability in RMR (R2 = 0.78, p < .001). In contrast, fat mass, the distance walked per day, and total T4 or TSH did not add predictive power to the model. Compared to men, a greater RMR per kg of LBM was observed in untreated hypertensive overweight and obese women, while this sex difference was not observed in patients treated with ACEI or ARBs. In conclusion, our results indicate that elevated RMR per kg of LBM may be normalized by antagonizing the renin-angiotensin system