Influence of phase I duration on phase II V̇o2 kinetics parameter estimates in older and young adults

2011 ◽  
Vol 301 (1) ◽  
pp. R218-R224 ◽  
Author(s):  
Juan M. Murias ◽  
Matthew D. Spencer ◽  
John M. Kowalchuk ◽  
Donald H. Paterson
Keyword(s):  
Young Adults ◽  
Phase I ◽  
Phase Ii ◽  
Moderate Intensity ◽  
Parameter Estimates ◽  
Moderate Intensity Exercise ◽  
Kinetics Parameters ◽  
Exercise Transitions ◽  
The Individual ◽  
Kinetics Parameter

Older adults (O) may have a longer phase I pulmonary O2 uptake kinetics (V̇o2p) than young adults (Y); this may affect parameter estimates of phase II V̇o2p. Therefore, we sought to: 1) experimentally estimate the duration of phase I V̇o2p (EE phase I) in O and Y subjects during moderate-intensity exercise transitions; 2) examine the effects of selected phase I durations (i.e., different start times for modeling phase II) on parameter estimates of the phase II V̇o2p response; and 3) thereby determine whether slower phase II kinetics in O subjects represent a physiological difference or a by-product of fitting strategy. V̇o2p was measured breath-by-breath in 19 O (68 ± 6 yr; mean ± SD) and 19 Y (24 ± 5 yr) using a volume turbine and mass spectrometer. Phase I V̇o2p was longer in O (31 ± 4 s) than Y (20 ± 7 s) ( P < 0.05). In O, phase II τV̇o2p was larger ( P < 0.05) when fitting started at 15 s (49 ± 12 s) compared with fits starting at the individual EE phase I (43 ± 12 s), 25 s (42 ± 10 s), 35 s (42 ± 12 s), and 45 s (45 ± 15 s). In Y, τV̇o2p was not affected by the time at which phase II V̇o2p fitting started (τV̇o2p = 31 ± 7 s, 29 ± 9 s, 30 ± 10 s, 32 ± 11 s, and 30 ± 8 s for fittings starting at 15 s, 25 s, 35 s, 45 s, and EE phase I, respectively). Fitting from EE phase I, 25 s, or 35 s resulted in the smallest CI τV̇o2p in both O and Y. Thus, fitting phase II V̇o2p from (but not constrained to) 25 s or 35 s provides consistent estimates of V̇o2p kinetics parameters in Y and O, despite the longer phase I V̇o2p in O.

Fat and carbohydrate metabolism during exercise in elderly and young subjects

1996 ◽  
Vol 271 (6) ◽  
pp. E983-E989 ◽  
Author(s):  
S. Sial ◽  
A. R. Coggan ◽  
R. Carroll ◽  
J. Goodwin ◽  
S. Klein
Keyword(s):  
Young Adults ◽  
Carbohydrate Metabolism ◽  
Relative Intensity ◽  
The Elderly ◽  
Absolute Intensity ◽  
Substrate Oxidation ◽  
Carbohydrate Oxidation ◽  
Moderate Intensity ◽  
Elderly Subjects ◽  
Moderate Intensity Exercise

We evaluated the effect of aging on fat and carbohydrate metabolism during moderate intensity exercise. Glycerol, free fatty acid (FFA), and glucose rate of appearance (Ra) in plasma and substrate oxidation were determined during 60 min of cycle ergometer exercise in six elderly (73 +/- 2 yr) and six young adults (26 +/- 2 yr) matched by gender and lean body mass. The elderly group was studied during exercise performed at 56 +/- 3% of maximum oxygen uptake, whereas the young adults were studied during exercise performed at the same absolute and at a similar relative intensity as the elderly subjects. Mean fat oxidation during exercise was 25-35% lower in the elderly subjects than in the young adults exercising at either the same absolute or similar relative intensities (P < 0.05). Mean carbohydrate oxidation in the elderly group was 35% higher than the young adults exercising at the same absolute intensity (P < 0.001) but 40% lower than the young adults exercising at the same relative intensity (P < 0.001). Average FFA Ra in the elderly subjects was 85% higher than in the young adults exercising at the same absolute intensity (P < 0.05) but 35% lower than the young adults exercising at a similar relative intensity (P < 0.05). We conclude that fat oxidation is decreased while carbohydrate oxidation is increased during moderate intensity exercise in elderly men and women. The shift in substrate oxidation was caused by age-related changes in skeletal muscle respiratory capacity because lipolytic rates and FFA availability were not rate limiting in the older subjects.

scholarly journals Inhibition of Nitric Oxide Synthase by L‐NAME Speeds Phase II Pulmonary V̇ O2 Kinetics in the Transition to Moderate‐Intensity Exercise in Man

2003 ◽  
Vol 552 (1) ◽  
pp. 265-272 ◽  
Author(s):  
Andrew M. Jones ◽  
Daryl P. Wilkerson ◽  
Katrien Koppo ◽  
Sally Wilmshurst ◽  
Iain T. Campbell
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Phase Ii ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Oxide Synthase

Pulmonary oxygen uptake kinetics

2017 ◽  
Author(s):  
Alan R Barker ◽  
Neil Armstrong
Keyword(s):  
Oxygen Uptake ◽  
Oxidative Phosphorylation ◽  
Children And Adolescents ◽  
Phase Ii ◽  
Slow Component ◽  
Moderate Intensity ◽  
Heavy Exercise ◽  
Moderate Intensity Exercise ◽  
Pulmonary Oxygen Uptake ◽  
Age Related

The pulmonary oxygen uptake (pV̇O2) kinetic response to exercise provides valuable non-invasive insight into the control of oxidative phosphorylation and determinants of exercise tolerance in children and adolescents. Few methodologically robust studies have investigated pV̇O2 kinetics in children and adolescents, but age- and sex-related differences have been identified. There is a clear age-related slowing of phase II pV̇O2 kinetics during heavy and very heavy exercise, with a trend showing during moderate intensity exercise. During heavy and very heavy exercise the oxygen cost is higher for phase II and the pV̇O2 component is truncated in children. Sex-related differences occur during heavy, but not moderate, intensity exercise, with boys having faster phase II pV̇O2 kinetics and a smaller pV̇O2 slow component compared to girls. The mechanisms underlying these differences are likely related to changes in phosphate feedback controllers of oxidative phosphorylation, muscle oxygen delivery, and/or muscle fibre recruitment strategies.

Enhanced muscle glucose metabolism after exercise in the rat: the two phases

1984 ◽  
Vol 246 (6) ◽  
pp. E471-E475 ◽  
Author(s):  
L. P. Garetto ◽  
E. A. Richter ◽  
M. N. Goodman ◽  
N. B. Ruderman
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Phase I ◽  
Phase Ii ◽  
Muscle Glycogen ◽  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Moderate Intensity ◽  
Base Line ◽  
Two Phases

Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity was still observed in perfused muscle; however, glucose utilization was also increased in the absence of added insulin (1.5 vs. 4.2 mumol X g-1 X h-1). In contrast 2.5 h after the run, muscle glycogen had returned to near preexercise values, and only the insulin-induced increase in glucose utilization was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have returned to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation.

Prior heavy-intensity exercise speeds V̇o2 kinetics during moderate-intensity exercise in young adults

2005 ◽  
Vol 98 (4) ◽  
pp. 1371-1378 ◽  
Author(s):  
Brendon J. Gurd ◽  
Barry W. Scheuermann ◽  
Donald H. Paterson ◽  
John M. Kowalchuk
Keyword(s):  
Young Adults ◽  
Lactate Threshold ◽  
Near Infrared ◽  
Linear Regression Analysis ◽  
Cycle Ergometer ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Warm Up ◽  
Total Hemoglobin ◽  
Concentration Changes

The effect of prior heavy-intensity warm-up exercise on subsequent moderate-intensity phase 2 pulmonary O2 uptake kinetics (τV̇o2) was examined in young adults exhibiting relatively fast (FK; τV̇o2 < 30 s; n = 6) and slow (SK; τV̇o2 > 30 s; n = 6) V̇o2 kinetics in moderate-intensity exercise without prior warm up. Subjects performed four repetitions of a moderate (Mod1)-heavy-moderate (Mod2) protocol on a cycle ergometer with work rates corresponding to 80% estimated lactate threshold (moderate intensity) and 50% difference between lactate threshold and peak V̇o2 (heavy intensity); each transition lasted 6 min, and each was preceded by 6 min of cycling at 20 W. V̇o2 and heart rate (HR) were measured breath-by-breath and beat-by-beat, respectively; concentration changes of muscle deoxyhemoglobin (HHb), oxyhemoglobin, and total hemoglobin were measured by near-infrared spectroscopy (Hamamatsu NIRO 300). τV̇o2 was lower ( P < 0.05) in Mod2 than in Mod1 in both FK (20 ± 5 s vs. 26 ± 5 s, respectively) and SK (30 ± 8 s vs. 45 ± 11 s, respectively); linear regression analysis showed a greater “speeding” of V̇o2 kinetics in subjects exhibiting a greater Mod1 τV̇o2. HR, oxyhemoglobin, and total hemoglobin were elevated ( P < 0.05) in Mod2 compared with Mod1. The delay before the increase in HHb was reduced ( P < 0.05) in Mod2, whereas the HHb mean response time was reduced ( P < 0.05) in FK (Mod2, 22 ± 3 s; Mod1, 32 ± 11 s) but not different in SK (Mod2, 36 ± 13 s; Mod1, 34 ± 15 s). We conclude that improved muscle perfusion in Mod2 may have contributed to the faster adaptation of V̇o2, especially in SK; however, a possible role for metabolic inertia in some subjects cannot be overlooked.

O2 uptake kinetics, pyruvate dehydrogenase activity, and muscle deoxygenation in young and older adults during the transition to moderate-intensity exercise

2008 ◽  
Vol 294 (2) ◽  
pp. R577-R584 ◽  
Author(s):  
B. J. Gurd ◽  
S. J. Peters ◽  
G. J. F. Heigenhauser ◽  
P. J. LeBlanc ◽  
T. J. Doherty ◽  
...  
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Pyruvate Dehydrogenase ◽  
Lactate Threshold ◽  
Time Course ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Similar Time ◽  
O2 Uptake Kinetics ◽  
The Relationship

The adaptation of pulmonary O2 uptake (V̇o2p) kinetics is slowed in older compared with young adults during the transition to moderate-intensity exercise. In this study, we examined the relationship between V̇o2p kinetics and mitochondrial pyruvate dehydrogenase (PDH) activity in young ( n = 7) and older ( n = 6) adults. Subjects performed cycle exercise to a work rate corresponding to ∼90% of estimated lactate threshold. Phase 2 V̇o2p kinetics were slower ( P < 0.05) in older (τ = 40 ± 17 s) compared with young (τ = 21 ± 6 s) adults. Relative phosphocreatine (PCr) breakdown was greater ( P < 0.05) at 30 s in older compared with young adults. Absolute PCr breakdown at 6 min was greater ( P < 0.05) in older compared with young adults. In young adults, PDH activity increased ( P < 0.05) from baseline to 30 s, with no further change observed at 6 min. In older adults, PDH activity during baseline exercise was similar to that seen in young adults. During the exercise transition, PDH activity did not increase ( P > 0.05) at 30 s of exercise but was elevated ( P < 0.05) after 6 min. The change in deoxyhemoglobin (HHb) was greater for a given V̇o2p in older adults, and there was a similar time course of HHb accompanying the slower V̇o2p kinetics in the older adults, suggesting a slower adaptation of bulk O2 delivery in older adults. In conclusion, the slower adaptation of V̇o2p in older adults is likely a result of both an increased metabolic inertia and lower O2 availability.

Phase I/II Clinical Trial of Erwinia Asparaginase (ErwinaseR) in Combination with Prednisolone, Vincristine and Pirarubicin in Children and Young Adults with Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3657-3657
Author(s):  
Chitose Ogawa ◽  
Atsushi Manabe ◽  
Hiroaki Goto ◽  
Katsuyoshi Koh ◽  
Daisuke Tomizawa ◽  
...  
Keyword(s):  
Young Adults ◽  
Phase I ◽  
Phase Ii ◽  
Safety And Efficacy ◽  
E Coli ◽  
Asparaginase Activity ◽  
Erwinia Asparaginase ◽  
Children And Young Adults ◽  
Level 1 ◽  
Grade 3

Abstract Introduction: L-asparaginase is an important component of multi-agent chemotherapy for children and young adults with ALL. In Japan, only one asparaginase preparation, native-E-coli-asparaginase (LeunaseR), has been approved so far by the Health, Labour and Welfare Ministry. The incidence of clinical allergy to native-E-coli -asparaginase can be more than 30% with repeated administration. To continue treatment with asparaginase, Erwinia asparaginase (ErwinaseR), deriving from Erwinia chrysanthemi, is recommended for patients who develop clinical allergy to native-E-coli-asparaginase, because the drug has no cross reactivity. We planned phase I/II trial OP-01-001 to investigate the safety and efficacy of Erwinase in combination chemotherapy consist of prednisolone, vincristine and pirarubicin. Patients and Methods: Eligible patients on this study were children and young adults with ALL/ LBL in remission, >=1 to =<25 years of age, and had developed allergy to E-coli-asparaginase. Patients with a history of pancreatitis or previous administration of Erwinase were excluded. The study was approved by IRB at each institution and patients/guardians provided informed consent/assent. In this trial regimen OP-01-001, level 1 (25,000) or level 0 (20,000 IU/m2) x 6 doses of Erwinase were planned to administer intramuscularly (IM) on day 2, 5, 7, 9, 11 and 13 with 40 mg/m2/day x15 days of prednisolone, 1.5mg/m2 x 3 doses of vincristine and 20 mg/m2x 2 doses of pirarubicin. In phase I, we determined the maximum tolerated dose, dose limiting toxicity (DLT), and the recommended phase II dose (RP2D) of Erwinase. Safety, efficacy and pharmacokinetic/dynamic study were evaluated in all patients. Blood samples were obtained at scheduled time points during Erwinase therapy and assayed for asparaginase activity and asparagine concentration in plasma. Primary endpoint was asparaginase activity in plasma at 48h after the first dosing. Results: A total of 24 eligible patients were enrolled to phase I/II study from February 2012 to January 2014. In phase I study, 6 eligible/evaluable patients were enrolled to level 1, starting at 25,000 IU/m2. Since all patients completed the scheduled treatments without DLT in level 1, RP2D was determined 25,000 IU/m2and 18 patients were enrolled in phase II study. PK, PD, safety and efficacy were evaluated as phase I/II study. The median age of 24 evaluated patients was 7.5 years (range 2-16) and 15 patients (62.5%) were male. In PK/PD study, one patient was excluded because essential clinical dataset was not obtained. After the first dosing, serum asparaginase activity exceeded 0.1 IU/mL in 23/23 patients (100%) at 48 hours and it did in 18/23 patients (78.3%) at 72 hours. After the sixth dosing, the activity at 72 hours was higher than 0.1 IU/mL in 19/23 (82.6%). Plasma asparagine was significantly depleted (<1.0 μM) in 22/23 (95.7%) 48 hours after the first dosing and it was also depleted in 22/23 (95.7%) 72 hours after the last dosing in all but one patients. All patients maintained remission status during the trial. No allergic reaction related to Erwinase was reported. Hypertriglyceridemia or blood triglycerides increased was reported in 12/24 (50%), 4 cases in grade 3 and 1 in grade 4. Increase in blood sugar was observed in 3 patients (12.5%), 2 in grade 1 and 1 in grade 2. In addition, 23 (95.8%) and 1 (4.2%) developed decrease in fibrinogen and increase in ammonia at grade 2-4. Grade 3 febrile neutropenia and bacteremia were reported in 8 patients (33.3%) and in 1 patient (4.2%), respectively. There were no reports of hemorrhage, thrombosis, pancreatitis, or death. Conclusion: Erwinase as administered using the OP-01-001 regimen was well tolerated without unexpected toxicities and achieved good serum asparaginase activity at both 48 and 72 hours after dosing. In previous reports, a much lower dose of Erwinase at 10,000 IU/m2/dose was used in the study of EORTC (Duval M. Blood 2002;99:2734), which was subsequently assessed as suboptimal and the identical dose of erwinase at 25,000 IU/m2/dose was used in the study of COG (Salzer WL. Blood 2013;122:507). We herein showed that following allergy to E-coli native-asparaginase, erwinase 25,000 IU/m2 x 6 doses IM in 2 or 3 days interval in 2 weeks was effective and safe in children and young adults in Japan. Disclosures Ogawa: OHARA Pharmaceutical Co., Ltd.: Honoraria. Manabe:OHARA Pharmaceutical Co., Ltd.: Honoraria. Fukushima:OHARA Pharmaceutical Co., Ltd.: Honoraria. Horibe:OHARA Pharmaceutical Co., Ltd.: Honoraria. Hamada:OHARA Pharmaceutical Co., Ltd.: Employment. Ohara:OHARA Pharmaceutical Co., Ltd.: Honoraria.

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