Impact of reduced cytochrome oxidase activity on peak oxygen consumption of muscle

1990 ◽  
Vol 69 (1) ◽  
pp. 384-389 ◽  
Author(s):  
R. M. McAllister ◽  
R. W. Ogilvie ◽  
R. L. Terjung

The impact of reduced muscle oxidative capacity on peak oxygen consumption and isometric performance was evaluated using an isolated rat hindlimb preparation perfused with a high oxygen delivery. Capacity for electron transport was reduced with chloramphenicol (CAP), an inhibitor of mitochondrial gene-coded protein synthesis. The activity of cytochrome oxidase, a mitochondrial cristae component, was reduced approximately 45% (P less than 0.005) in the mixed-fiber-type plantaris muscle. Several facets of muscle remodeling were also evident with the 10- to 14-day CAP treatment, including decreased citrate synthase activity, increased capillarity, and increased numbers of type IIc fibers. Perfusion of CAP (n = 6) and control (n = 7) rat hindlimbs of similar size with similar total flows (10-11 ml/min) and oxygen contents (20-21 vol%) resulted in similarly high oxygen deliveries to contracting muscles of the hindlimbs (CAP, 9.66 +/- 0.83 mumols.min-1.g-1; control, 8.74 +/- 0.75). Performance of the gastrocnemius-plantaris-soleus group declined in a similar fashion for both groups during increasingly intense near-steady-state tetanic contraction (100 ms at 100 Hz) conditions of 4, 8, 15, 30, 45, and 60 per minute. Oxygen consumption was similar for both groups at rest and increased similarly at each contraction condition. Peak oxygen consumption was not different between CAP (5.34 +/- 0.55 mumols.min-1.g-1) and control (5.74 +/- 0.43) groups and required only 56-68% of the oxygen delivered. This implies that rat skeletal muscle can suffer a significant reduction in its electron transport capacity without impairing peak oxygen consumption and muscle performance.(ABSTRACT TRUNCATED AT 250 WORDS)

1991 ◽  
Vol 70 (4) ◽  
pp. 1569-1574 ◽  
Author(s):  
R. M. McAllister ◽  
R. L. Terjung

An isolated perfused rat hindlimb preparation was used to study the impact of local muscle adaptations induced by endurance exercise training on muscle performance and peak muscle oxygen consumption. Rats were trained for 12-15 wk by a running program (30 m/min up a 15% grade for 1 h/day 5 days/wk) shown previously to increase muscle mitochondrial enzyme activity. Sedentary (n = 11) and trained (n = 11) hindlimbs of similar size were perfused with a similar inflow (12.1 ml/min) at a similar oxygen content (18.1 ml O2/100 ml blood). Tetanic contractions (100 ms at 100 Hz) at 4, 8, 15, 30, 45, and 60/min were elicited in consecutive order. Initial tension was better maintained by muscles of trained animals at all frequencies above 4 tetani/min (P less than 0.05). Oxygen consumption (mumol.min-1.g-1) increased similarly in both groups at the lower contraction frequencies but was greater (P less than 0.05) in the trained [3.52 +/- 0.32 (SE)] than in the sedentary (2.44 +/- 0.31) group at 60 tetani/min. The peak oxygen consumption of the trained group (3.93 +/- 0.27) was 20% greater (P less than 0.05) than that of the sedentary group (3.28 +/- 0.28) when peak values for each animal, irrespective of the contraction condition, are compared. Blood flows to the contracting muscle (approximately 100 ml.min-1.g-1) and, therefore, oxygen deliveries (mumol.min-1.g-1) were not different between sedentary (7.99 +/- 0.56) and trained groups (8.35 +/- 0.61). Thus the 20% higher peak oxygen consumption was achieved by a greater oxygen extraction.(ABSTRACT TRUNCATED AT 250 WORDS)


1990 ◽  
Vol 259 (6) ◽  
pp. C889-C896 ◽  
Author(s):  
R. M. McAllister ◽  
R. L. Terjung

Electron transport capacity of skeletal muscle was inhibited in situ in an acute dose-dependent manner with myxothiazol, a tight-binding inhibitor of ubiquinone-cytochrome c reductase, complex III of the respiratory chain. Peak oxygen consumption of rat hindlimb muscle was determined via consecutive 10-min isometric contraction (100 ms at 100 Hz) periods of increasing energy demands (4, 8, 15, 30, 45, and 60 tetani/min), using an isolated hindlimb preparation perfused with a high oxygen delivery (approximately 6-8 mumol.min-1.g-1). Peak oxygen consumption decreased from 4.61 +/- 0.19 mumol.min-1.g-1 (control) in a dose-dependent manner to 0.73 +/- 0.07 mumol.min-1.g-1 at 0.50 microM myxothiazol in blood. Oxygen extraction decreased from 65 to 12% of delivered oxygen. Furthermore, the reduction in peak respiratory rate became evident at lower energy demands of the contraction sequence. Myxothiazol inhibition of respiration was not dependent on the presence of muscle contractions but was evident when mitochondria were uncoupled with carbonyl cyanide m-chlorophenylhydrazone. A 50% effective dosage (ED50) of 0.21 microM myxothiazol for inhibition of peak oxygen consumption closely resembled the inhibition of NADH-cytochrome c reductase activity (ED50 of 0.27 microM) determined from homogenates of the same muscles. This suggests that the peak oxygen consumption of skeletal muscle is tightly coupled to the capacity for electron transport evaluated by flux through NADH-cytochrome c reductase. If the enzyme activity measured in vitro correctly represents available enzymatic capacity within contracting muscle, approximately 75% of electron transport capacity for handling reducing equivalents generated from NADH is utilized during peak oxygen consumption of rat hindlimb muscle contracting in situ.


1998 ◽  
Vol 275 (3) ◽  
pp. E487-E494 ◽  
Author(s):  
Anne Raben ◽  
Elsebeth Mygind ◽  
Arne Astrup

Muscle fiber morphology and activities of four key enzymes, as well as energy metabolism, were determined in nine normal-weight postobese women and nine matched control subjects. No differences in fiber type composition, but a smaller mean fiber area and area of fiber types I and IIb, were found in postobese compared with control subjects ( P < 0.05). The activities of β-hydroxyacyl-CoA dehydrogenase (HADH) and citrate synthase (CS) were 20% lower in postobese than in control subjects ( P < 0.05). However, the activities of lactate dehydrogenase and lipoprotein lipase were not significantly different between postobese and control subjects. Basal metabolic rate and respiratory exchange ratio were also similar, but maximal oxygen uptake (V˙o 2 max) tended to be lower in postobese than in control subjects ( P = 0.06). When adjustments were made for differences inV˙o 2 max, HADH and CS were not different between postobese and control subjects. In conclusion, these data suggest that smaller fiber areas and lower enzyme activities, i.e., markers of aerobic capacity of skeletal muscle, but not fiber composition, may be factors predisposing to obesity.


2017 ◽  
Vol 38 (4) ◽  
pp. 630-638 ◽  
Author(s):  
Brittany A. Edgett ◽  
Jacob T. Bonafiglia ◽  
James P. Raleigh ◽  
Mario P. Rotundo ◽  
Matthew D. Giles ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 836
Author(s):  
Joerg Lindenmann ◽  
Nicole Fink-Neuboeck ◽  
Melanie Fediuk ◽  
Alfred Maier ◽  
Gabor Kovacs ◽  
...  

The peak oxygen consumption (VO2 peak) serves as a prognostic factor in cardio-respiratory diseases and plays an important role in cancer patients. The long-term prognostic relevance of VO2 peak in lung cancer patients has not been investigated extensively. The aim of this study was to evaluate the impact of the preoperative VO2 peak on the postoperative long-term survival in patients with operated lung cancer. Retrospective analysis of 342 patients with curatively resected non-small-cell lung cancer using a multivariate Cox proportional hazard model. Results: Preoperative VO2 peak ranged from 10.2 to 51.8 mL/kg/min (mean: 18.3 ± 4.6), VO2 peak % of predicted ranged from 32 to 172% (mean: 65.2 ± 18.0%). Overall 10-year survival was 23%. A Log-rank test comparing predicted VO2 peak ≥ 60% with predicted VO2 peak < 60% showed overall survival of 30% and 17%, respectively (p < 0.001) and non-tumour-related survival of 71% and 51% (p = 0.001) at 10 years. In multivariable Cox analysis, overall 10-year survival correlated with a high predicted VO2 peak% (p = 0.001) and low N-stage corresponding to N0 and N1 (p < 0.001). Non-tumour-related death correlated with low VO2 peak% of predicted (p = 0.001), and age (p < 0.001). Low preoperative VO2 peak was associated with both decreased postoperative overall survival and decreased non-tumour-related survival during the 10-year follow-up.


2019 ◽  
Vol 97 (8) ◽  
pp. 3193-3198 ◽  
Author(s):  
Christine M Latham ◽  
Clara K Fenger ◽  
Sarah H White

Abstract Responses of equine skeletal muscle characteristics to growth and training have been shown to differ between breeds. These differential responses may arise in part because muscle fiber type and mitochondrial density differ between breeds, even in untrained racing-bred horses. However, it is not known when these breed-specific differences manifest. To test the hypothesis that weanling Standardbreds (SB) and Thoroughbreds (TB) would have higher mitochondrial measures than Quarter Horses (QH), gluteus medius samples were collected from SB (mean ± SD; 6.2 ± 1.0 mo; n = 10), TB (6.1 ± 0.5 mo; n = 12), and QH (7.4 ± 0.6 mo; n = 10). Citrate synthase (CS) and cytochrome c oxidase (CCO) activities were assessed as markers of mitochondrial density and function, respectively. Mitochondrial oxidative (P) and electron transport system (E) capacities were assessed by high-resolution respirometry (HRR). Data for CCO and HRR are expressed as integrated (per mg protein and per mg tissue wet weight, respectively) and intrinsic (per unit CS). Data were analyzed using PROC MIXED in SAS v 9.4 with breed as a fixed effect. Mitochondrial density (CS) was higher for SB and TB than QH (P ≤ 0.0007). Mitochondrial function (integrated and intrinsic CCO) was higher in TB and QH than SB (P ≤ 0.01). Integrated CCO was also higher in TB than QH (P &lt; 0.0001). However, SB had higher integrated maximum P (PCI+II) and E (ECI+II) than QH (P ≤ 0.02) and greater integrated and intrinsic complex II-supported E (ECII) than both QH and TB (P ≤ 0.02), whereas TB exhibited higher integrated P with complex I substrates (PCI) than SB and QH (P ≤ 0.003) and higher integrated PCI+II and ECI+II than QH (P ≤ 0.02). In agreement, TB and QH had higher contribution of complex I (CI) to max E than SB (P ≤ 0.001), whereas SB had higher contribution of CII than QH and TB (P ≤ 0.002). Despite having higher mitochondrial density than QH and TB, SB showed lower CCO activity and differences in contribution of complexes to oxidative and electron transport system capacities. Breed differences in mitochondrial parameters are present early in life and should be considered when developing feeding, training, medication, and management practices.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Anneke van Biljon ◽  
Glynis Longhurst ◽  
Ina Shaw ◽  
Brandon Stuwart Shaw

Background: Exergaming is an ideal vehicle for promoting regular physical activity among children who may be reluctant to participate in traditional types of exercise. Objectives: The purpose of this study was to investigate the effects of six weeks of exergaming and traditional video gaming on body composition and cardiovascular fitness variables among overweight and obese children. Methods: Thirty-one overweight and obese children (11.40 ± 0.86 years) were recruited from three primary schools in KwaZulu Natal, South Africa. Participants were assigned to either an exergaming group (n = 11), traditional gaming group (n = 10) or control group (n = 10). Body composition variables (body mass index (BMI), waist-to-hip ratio (WHR)) and cardiovascular fitness variables (resting heart rate (RHR), resting systolic (SBP) and diastolic blood pressure (DBP) and peak oxygen consumption (VO2peak)) were measured. A paired sample t-test was used to determine changes from baseline to post-assessment within each group. Results: No significant improvements were observed in BMI percentile among the exergaming group (P = 0.25), traditional gaming group (P = 0.06) and control group (P = 0.25). Waist-to-hip ratio significantly decreased following exergaming (P = 0.050), but not following traditional gaming (P = 0.060) and in control group (P = 0.200). Significant improvement in RHR was found in the exergaming group (P = 0.010), but none in the traditional gaming group (P = 0.280) and control group (P = 0.720). No significant improvements were noted in resting SBP following exergaming (P = 0.790), traditional video gaming (P = 0.730) and in the control group (P = 0.610). Diastolic blood pressure did not significantly improve in the exergaming group (P = 0.070), traditional video gaming group (P = 0.360) or control group (P = 0.100). Peak oxygen consumption (VO2peak) did not significantly improve in the exergaming group (P = 0.830), traditional gaming group (P = 0.710) or control group (P = 0.450). Conclusions: Findings indicate that six weeks of exergaming induced favorable changes in waist-to-hip ratio and RHR among overweight and obese children. Thereby demonstrating that non-traditional modes of exercise such as exergaming can be used as an alternative to traditional modes of exercise to induce somebody composition and cardiovascular changes.


2019 ◽  
Vol 5 (5) ◽  
pp. e359 ◽  
Author(s):  
Areej Mahjoub ◽  
Zuzana Cihlarova ◽  
Martine Tétreault ◽  
Lauren MacNeil ◽  
Neal Sondheimer ◽  
...  

ObjectiveTo investigate the pathogenicity of a novel homozygous BRAT1 variant in 2 siblings with nonprogressive cerebellar ataxia (NPCA) through functional studies on primary and immortalized patient cell lines.MethodsBRAT1 protein levels and ataxia-telangiectasia mutated (ATM) kinase activity in patient-derived and control cell lines were assessed by Western blotting. The impact of the novel BRAT1 variants on mitochondrial function was also assessed, by comparing patient and control cell lines for rates of oxygen consumption and for phosphorylation (S293) of the E1⍺ subunit of pyruvate dehydrogenase (PDH).ResultsTwo male siblings with NPCA, mild intellectual disability, and isolated cerebellar atrophy were found to be homozygous for a c.185T>A (p.Val62Glu) variant in BRAT1 by whole exome sequencing. Western blotting revealed markedly decreased BRAT1 protein levels in lymphocytes and/or fibroblast cells from both affected siblings compared to control cell lines. There were no differences between the patient and control cells in ATM kinase activation, following ionizing radiation. Mitochondrial studies were initially suggestive of a defect in regulation of PDH activity, but there was no evidence of increased phosphorylation of the E1⍺ subunit of the PDH complex. Measurement of oxygen consumption rates similarly failed to identify differences between patient and control cells.ConclusionsBiallelic pathogenic variants in BRAT1 can be associated with NPCA, a phenotype considerably milder than previously reported. Surprisingly, despite the molecular role currently proposed for BRAT1 in ATM regulation, this disorder is unlikely to result from defective ATM kinase or mitochondrial dysfunction.


2020 ◽  
pp. 1-8
Author(s):  
Jianli Niu ◽  
Aliana Godoy ◽  
Talya Kadish ◽  
Bibhuti B. Das

Abstract Objectives: We evaluated the impact of peak respiratory exchange ratio on the prognostic values of cardiopulmonary exercise variables during symptoms-limited incremental exercise tests in patients with Fontan physiology. Methods: Retrospective single-centre chart review study of Fontan patients who underwent exercise testing using the Bruce protocol between 2014 and 2018 and follow-up. Results: A total of 34 patients (age > 18 years) had a Borg score of ≥7 on the Borg 10-point scale, but only 50% of patients achieved a peak respiratory exchange ratio of ≥ 1.10 (maximal test). Peak oxygen consumption, percent-predicted peak oxygen consumption, and peak oxygen consumption at the ventilatory threshold was reduced significantly in patients with a peak respiratory exchange ratio of < 1.10. Peak oxygen consumption and percent-predicted peak oxygen consumption was positively correlated with peak respiratory exchange ratio values (r = 0.356, p = 0.039). After a median follow-up of 21 months, cardiac-related events occurred in 16 (47%) patients, with no proportional differences in patients due to their respiratory exchange ratio (odds ratio, 0.62; 95% CI: 0.18–2.58; p = 0.492). Multivariate Cox proportional hazard analysis showed percent-predicted peak oxygen consumption, peak heart rate, and the oxygen uptake efficient slope were highly related to the occurrence of events in patients only with a peak respiratory exchange ratio of ≥ 1.10. Conclusions: The value of peak cardiopulmonary exercise variables is limited for the determination of prognosis and assessment of interventions in Fontan patients with sub-maximal effort. Our findings deserve further research and clinical application.


Sign in / Sign up

Export Citation Format

Share Document