Studies of preoperative cardiopulmonary exercise testing (CPET) have shown that a reduced oxygen uptake at anaerobic threshold (AT) and elevated ventilatory equivalent for carbon dioxide (VE/VCO2) ...were associated with reduced short- and medium-term survival after major surgery. The aim of this study was to determine the relative values of these, and also clinical risk factors, in identifying patients at risk of death after major intra-abdominal, non-vascular surgery.
Patients aged >55 yr, undergoing elective colorectal resection, radical nephrectomy, or cystectomy between June 2004 and May 2009 had CPET during their routine pre-assessment clinic visit. We performed a retrospective analysis of known clinical risk factors and data from CPET to assess their relationship to all-cause mortality after surgery.
Eight hundred and forty-seven patients underwent surgery, of whom 18 (2.1%) died. A clinical history of ischaemic heart disease (RR 3.1, 95% CI 1.3–7.7), a VE/VCO2 >34 (RR 4.6, 95% CI 1.4–14.8), and an AT ≤10.9 ml kg−1 min−1 (RR 6.8, 95% CI 1.6–29.5) were all significant predictors of all-cause hospital and 90 day mortality. The effect of reduced AT was most pronounced in patients with no history of cardiac risk factors (RR 10.0, 95% CI 1.7–61.0).
The routine measurement of AT and VE/VCO2 using CPET for patients undergoing high-risk surgery can accurately identify the majority of high-risk patients, while the use of clinical risk factors alone will only identify a relatively small proportion of at-risk patients.
The aim of this paper was to identify the most appropriate allometric scaling model for expressing aerobic fitness, determined by maximal oxygen consumption (VO2max), that would allow comparisons ...across differing body types.
VO2max and body composition data were collected from untrained non-obese and obese participants (N.=126). Allometric models were created using body mass (BM), fat-free mass (FFM), and leg FFM (LFFM) to determine the goodness-of-fit using the Akaike Information Criterion (AIC).
Allometric scaled exponents adjusted for BM, FFM and LFFM were 0.67, 0.68 and 0.55, respectively. VO2max scaled to BM was 22% higher in non-obese individuals. Scaled to LFFM, V VO2max was only 7.5% higher in non-obese individuals as compared to obese individuals. Data showed a positive correlation (r=0.28; P=0.009) between VO2max and BM for non-obese participants and a negative correlation (r=-0.39; P=0.014) for obese participants. AIC values showed the LFFM model as the best fit (AICc = 0 "substantial support) and the AIC differences for FFM and BM were both >10 "no support" for the model (12.1 and 28.2, respectively).
Interpretation of aerobic power and comparisons would be most appropriate when allometrically scaled to the metabolically active tissue (LFFM). Bias is introduced when scaling to BM and comparing individuals of various body compositions.
Aerobic exercise reduces blood pressure (BP), but it is unknown whether a high-intensity training approach can elicit a greater BP reduction in populations with elevated BP. This systematic review ...compared the efficacy of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) for reducing BP in adults with pre- to established hypertension.
Five electronic databases (MEDLINE, EMBASE, CENTRAL, PEDro, and SPORTDiscus) were searched for randomized trials comparing the chronic effects of HIIT versus MICT on BP in individuals with resting systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 85 mmHg and/or under antihypertensive medication. Random-effects modelling was used to compare changes from pre- to post-intervention in resting and ambulatory BP between HIIT and MICT. Changes from pre- to post-intervention in maximal oxygen uptake (Formula: see textO
) between HIIT and MICT were also meta-analyzed. Data were reported as weighted mean difference (MD) and 95% confidence interval (CI).
Ambulatory BP was excluded from the meta-analysis due to the limited number of studies (two studies). Comparing changes from pre- to post-intervention, no differences in resting systolic BP (MD - 0.22 mmHg CI 95%, - 5.36 to 4.92, p = 0.93, I
= 53%) and diastolic BP (MD - 0.38 mmHg CI 95%, - 3.31 to 2.54, p = 0.74, I
= 0%) were found between HIIT and MICT (seven studies; 164 participants). HIIT improved Formula: see textO
to a greater magnitude than MICT (MD 2.13 ml/kg/min CI 95%, 1.00 to 3.27, p < 0.01, I
= 41%) with similar completion rates of the intervention and attendance at the exercise training sessions (nine studies; 245 participants). Limited data were available to compare the incidence of adverse events between HIIT and MICT.
HIIT and MICT provided comparable reductions in resting BP in adults with pre- to established hypertension. HIIT was associated with greater improvements in Formula: see textO
when compared to MICT. Future randomized trials should investigate the efficacy of HIIT versus MICT for reducing ambulatory BP in adults with pre- to established hypertension.
PROSPERO registration (2016: CRD42016041885).
The rate at which cells acidify the extracellular medium is frequently used to report glycolytic rate, with the implicit assumption that conversion of uncharged glucose or glycogen to lactate(-)+H(+) ...is the only significant source of acidification. However, another potential source of extracellular protons is the production of CO2 during substrate oxidation: CO2 is hydrated to H2CO3, which then dissociates to HCO3(-)+H(+).
O2 consumption and pH were monitored in a popular platform for measuring extracellular acidification (the Seahorse XF Analyzer).
We found that CO2 produced during respiration caused almost stoichiometric release of H(+) into the medium. With C2C12 myoblasts given glucose, respiration-derived CO2 contributed 34% of the total extracellular acidification. When glucose was omitted or replaced by palmitate or pyruvate, this value was 67-100%. Analysis of primary cells, cancer cell lines, stem cell lines, and isolated synaptosomes revealed contributions of CO2-produced acidification that were usually substantial, ranging from 3% to 100% of the total acidification rate.
Measurement of glycolytic rate using extracellular acidification requires differentiation between respiratory and glycolytic acid production.
The data presented here demonstrate the importance of this correction when extracellular acidification is used for quantitative measurement of glycolytic flux to lactate. We describe a simple way to correct the measured extracellular acidification rate for respiratory acid production, using simultaneous measurement of oxygen consumption rate.
Extracellular acidification is often assumed to result solely from glycolytic lactate production, but respiratory CO2 also contributes. We demonstrate that extracellular acidification by myoblasts given glucose is 66% glycolytic and 34% respiratory and describe a method to differentiate these sources.
Abstract
The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its ...effectiveness is often limited by the high metabolic demand for O
2
by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O
2
nanoeconomizer pHPFON-NO/O
2
to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O
2
interacts with the acidic tumor microenvironment to release NO for endogenous O
2
conservation; second, it releases O
2
in response to mild photothermal effect to enable exogenous O
2
infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This “reducing expenditure of O
2
and broadening sources” strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.
We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased ...mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in
, which encodes the β subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, resulting in high rates of mitochondrial respiration. Expression of the mutant allele in human cell lines recapitulates this phenotype. These data support an autosomal dominant mitochondrial uncoupling syndrome with hypermetabolism. (Funded by the National Institutes of Health.).
Recent reports have identified a phenomenon by which hypoxia shifts glutamine metabolism from oxidation to reductive carboxylation. We now identify the mechanism by which HIF-1 activation results in ...a dramatic reduction in the activity of the key mitochondrial enzyme complex α ketoglutarate dehydrogenase (αKGDH). HIF-1 activation promotes SIAH2 targeted ubiquitination and proteolysis of the 48 kDa splice variant of the E1 subunit of the αKGDH complex (OGDH2). Knockdown of SIAH2 or mutation of the ubiquitinated lysine residue on OGDH2 (336KA) reverses the hypoxic drop in αKGDH activity, stimulates glutamine oxidation, and reduces glutamine-dependent lipid synthesis. 336KA OGDH2-expressing cells require exogenous lipids or citrate for growth in hypoxia in vitro and fail to grow as model tumors in immunodeficient mice. Reversal of hypoxic mitochondrial function may provide a target for the development of next-generation anticancer agents targeting tumor metabolism.
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•HIF-1 activation reduces mitochondrial OCR while generating anabolic precursors•Hypoxia reduces glutamine oxidation through SIAH2-dependent proteolysis of OGDH2•Active OGDH2 makes cells dependent on exogenous lipids for hypoxic growth•Expression of nondegradable OGDH2 blocks the growth of model tumors
Sun and Denko identify a mechanism by which hypoxia redirects the metabolism of glutamine away from mitochondrial oxidation toward the synthesis of cellular fatty acids in order to support tumor cell proliferation. This work suggests that redirecting the intracellular fate of glutamine may be an effective anticancer therapy.
The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers ...was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO
max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD -0.52, 95% CI -0.89 to -0.16; p<0.01) and fasting glucose (SMD -0.35, 95% CI -0.62 to -0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD -0.20, 95% CI -0.38 to -0.01; p<0.05), % body fat (SMD -0.40, 95% CI -0.74 to -0.06; p<0.05), VO
max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD -0.33, 95% CI -0.56 to -0.09; p<0.01), systolic blood pressure (SMD -0.35, 95% CI -0.60 to -0.09; p<0.01) and DBP (SMD -0.38, 95% CI -0.65 to -0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO
max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO
max and improve some cardiometabolic risk factors in overweight/obese populations.
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