Correlations between Lung-Transfer Factor, Ventilation, and Cardiac Output during Exercise

Rampulla, C; Marconi, C.; Beulcke, G; Amaducci, S

doi:10.1159/000193758

Cited by 7 publications

(3 citation statements)

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“…The ratio of alveolar ventilation rate to cardiac output (QPC/QCC) is 0.9 in the former case and 1.1 in the latter case. This increase in ratio is consistent with expectations for modestly more active rats if one assumes that the ventilation-perfusion ratio in rodents behaves similarly to the ratio in exercising humans (Rampulla et al, 1976).…”

Section: Discussionsupporting

confidence: 86%

“…The resultant ventilation perfusion ratio (QPC/QCC, i.e. 22.4/13.2) is 1.7 which is consistent with the expected change in ratio with exercise (Rampulla et al, 1976). It was decided to vary QPC rather than other parameters because QPC is a highly influential parameter and ventilation rate can vary readily and considerably in response to various stimuli.…”

Section: Discussionsupporting

confidence: 60%

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Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Kenyon

Benignus

Eklund

et al. 2008

Journal of Toxicology and Environmental Health, Part A

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Toluene is found in petroleum-based fuels and used as a solvent in consumer products and industrial applications. The critical effects following inhalation exposure involve the brain and nervous system in both humans and experimental animals, whether exposure duration is acute or chronic. The goals of this physiologically based pharmacokinetic (PBPK) model development effort were twofold: (1) to evaluate and explain the influence of feeding status and activity level on toluene pharmacokinetics utilizing our own data from toluene-exposed Long Evans (LE) rats, and (2) to evaluate the ability of the model to simulate data from the published literature and explain differing toluene kinetics. Compartments in the model were lung, slowly and rapidly perfused tissue groups, fat, liver, gut, and brain; tissue transport was blood-flow limited and metabolism occurred in the liver. Chemical-specific parameters and initial organ volumes and blood flow rates were obtained from the literature. Sensitivity analysis revealed that the single most influential parameter for our experimental conditions was alveolar ventilation; other moderately influential parameters (depending upon concentration) included cardiac output, rate of metabolism, and blood flow to fat. Based on both literature review and sensitivity analysis, other parameters (e.g., partition coefficients and metabolic rate parameters) were either well defined (multiple consistent experimental results with low variability) or relatively noninfluential (e.g. organ volumes). Rats that were weight-maintained compared to free-fed rats in our studies could be modeled with a single set of parameters because feeding status did not have a significant impact on toluene pharmacokinetics. Heart rate (HR) measurements in rats performing a lever-pressing task indicated that the HR increased in proportion to task intensity. For rats acclimated to eating in the lab during the day, both sedentary rats and rats performing the lever-pressing task required different alveolar ventilation rates to successfully predict the data. Model evaluation using data from diverse sources together with statistical evaluation of the resulting fits revealed that the model appropriately predicted blood and brain toluene concentrations with some minor exceptions. These results (1) emphasize the importance of experimental conditions and physiological status in explaining differing kinetic data, and (2) demonstrate the need to consider simulation conditions when estimating internal dose metrics for toxicity studies in which kinetic data were not collected.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 60%

Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Kenyon

Benignus

Eklund

et al. 2008

Journal of Toxicology and Environmental Health, Part A

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“…In health, this expansion of the alveolar–capillary layer results in a nearly linear rise in lung diffusing capacity for carbon monoxide (DLCO) with cardiac output (Q) as exercise intensity increases. 2 …”

Section: Introductionmentioning

confidence: 99%

Alveolar–capillary reserve during exercise in patients with chronic obstructive pulmonary disease

Behnia

Wheatley

Avolio

et al. 2017

COPD

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BackgroundFactors limiting exercise in patients with COPD are complex. With evidence for accelerated pulmonary vascular aging, destruction of alveolar–capillary bed, and hypoxic pulmonary vasoconstriction, the ability to functionally expand surface area during exercise may become a primary limitation.PurposeTo quantify measures of alveolar–capillary recruitment during exercise and the relationship to exercise capacity in a cohort of COPD patients.MethodsThirty-two subjects gave consent (53% male, with mean ± standard deviation age 66±9 years, smoking 35±29 pack-years, and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of 0–4: 2.3±0.8), filled out the St George’s Respiratory Questionnaire (SGRQ) to measure quality of life, had a complete blood count drawn, and underwent spirometry. The intrabreath (IB) technique for lung diffusing capacity for carbon monoxide (IBDLCO) and pulmonary blood flow (IBQc, at rest) was also performed. Subsequently, they completed a cycle ergometry test to exhaustion with measures of oxygen saturation and expired gases.ResultsBaseline average measures were 44±21 for SGRQ score and 58±11 for FEV1/FVC. Peak oxygen consumption (VO2) was 11.4±3.1 mL/kg/min (49% predicted). The mean resting IBDLCO was 9.7±5.4 mL/min/mmHg and IBQc was 4.7±0.9 L/min. At the first workload, heart rate (HR) increased to 92±11 bpm, VO2 was 8.3±1.4 mL/kg/min, and IBDLCO and IBQc increased by 46% and 43%, respectively, compared to resting values (p,0.01). The IBDLCO/Qc ratio averaged 2.0±1.1 at rest and remained constant during exercise with marked variation across subjects (range: 0.8–4.8). Ventilatory efficiency plateaued at 37±5 during exercise, partial pressure of mix expired CO2/partial pressure of end tidal CO2 ratio ranged from 0.63 to 0.67, while a noninvasive index of pulmonary capacitance, O2 pulse × PetCO2 (GxCap) rose to 138%. The exercise IBDLCO/Qc ratio was related to O2 pulse (VO2/HR, r=0.58, p<0.01), and subjects with the highest exercise IBDLCO/Qc ratio or the greatest rise from rest had the highest peak VO2 values (r=0.65 and 0.51, respectively, p<0.05). Of the noninvasive gas exchange measures of pulmonary vascular function, GxCap was most closely associated with DLCO, DLCO/Qc, and VO2 peak.ConclusionCOPD patients who can expand gas exchange surface area as assessed with DLCO during exercise relative to pulmonary blood flow have a more preserved exercise capacity.

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Gas Exchange in Exercise

Cerretelli

Prampero

1987

Comprehensive Physiology

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Correlations between Lung-Transfer Factor, Ventilation, and Cardiac Output during Exercise

Cited by 7 publications

References 3 publications

Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Alveolar–capillary reserve during exercise in patients with chronic obstructive pulmonary disease

Gas Exchange in Exercise

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Correlations between Lung-Transfer Factor, Ventilation, and Cardiac Output during Exercise

Cited by 7 publications

References 3 publications

Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Alveolar&shy;&ndash;capillary reserve during exercise in patients with chronic obstructive pulmonary disease

Gas Exchange in Exercise

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Product

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Alveolar–capillary reserve during exercise in patients with chronic obstructive pulmonary disease