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Biomedical subjects

W C Stanley

Publications and source records attributed to W C Stanley.

At least 55 records · Page 3Linked to original sources
PubMed1990

Tracer mixing: sites of tracer infusion and sampling.

Controversy exists in the literature concerning the correct infusion and sampling sites in studies measuring substrate turnover rates. To investigate this problem, we examined the results obtained with various infusion and sampling sites in 7 anesthetized dogs. [1-14C]lactate was infused by a primed continuous infusion method in three different sites (the left ventricle, ascending aorta, and the aortic arch) in a sequential fashion; samples were obtained simultaneously from five sites (femoral artery, carotid artery, pulmonary artery, superior vena cava and inferior vena cava) for each of the three different infusion sites. [U-13C]lactate was also infused in a femoral vein and simultaneous samples were obtained in the carotid artery and femoral artery for analysis of the stable isotope. [14C]lactate analysis demonstrated that infusion of the tracer into the left ventricular chamber resulted in a uniform distribution in the systemic circulation. Infusion into the ascending aorta near the aortic valve resulted in uniform distribution of tracer in four out of five experiments. Tracer infusion into the aortic arch resulted in nonuniform systemic distribution of tracer. The [U-13C]lactate results showed that infusion into the femoral vein gives uniform systemic distribution, similar to that observed with left ventricular infusion. The pulmonary artery lactate specific activities varied from those in the superior vena cava. Thus, this study shows that the tracer must be infused in the left ventricle or upstream from this chamber to obtain optimal systemic distribution. Vena caval sampling, especially superior vena caval sampling, will not give a consistent mixed venous concentration of the lactate tracer. Therefore, aortic tracer infusion with vena caval sampling may lead to errors in determining substrate turnover values.

Animals↗
PubMed1990

Increased lactate appearance and reduced clearance during hypoxia in dogs.

In order to assess the effects of severe hypoxia on whole body glucose and lactate kinetics, nine experiments were performed on anesthetized, ventilated mongrel dogs. [U-13C]glucose and [1-14C]lactate (n = 5), or [6-14C]glucose and [U-13C]lactate (n = 4) were infused using the primed-continuous infusion method. Cardiac output was measured by thermodilution. After a control period with 21% O2, inspired O2 was reduced for 90 minutes. Three of the experiments resulted in unstable hemodynamics and lactate levels, and are excluded from the mean data. Arterial PO2 fell from a control level of 106.8 +/- 11.9 to 24.2 +/- 3.5 mmHg during the last 45 minutes of hypoxia, and O2 transport fell to 52% of normoxic values. Arterial lactate concentration and the rate of appearance increased by 428% and 182%, respectively, from control to hypoxia. The metabolic clearance rate for lactate fell by 34%. Arterial glucose levels did not change significantly with hypoxia, but the rate of glucose disappearance rose by 70%, and the rate of glucose conversion to lactate increased 3-fold. It is concluded that acute severe hypoxia in anesthetized dogs causes 1) a large increase in arterial lactate levels, but no significant change in glycemia, 2) a large increase in the rate of lactate disappearance and only a small increase in the rate of glucose disappearance and 3) a fall in the metabolic clearance rate of lactate.

Animals↗
PubMed1990

Effects of acute hyperglycemia on myocardial glycolytic activity in humans.

The effects of hyperglycemia on myocardial glucose metabolism were investigated in seven healthy male subjects (age 24 +/- 4 yr). [6-14C]Glucose and [U-13C]lactate were infused as tracers. Circulating glucose was elevated to two hyperglycemic levels using a clamp technique for 1 h at each level. The mean arterial glucose concentration was 4.95 +/- 0.29 (control), 8.33 +/- 0.31 and 10.84 +/- 0.60 mumols/ml, respectively. Glucose extraction increased significantly from control (0.15 +/- 0.13 mumols/ml) during each level of the glucose clamp (0.28 +/- 0.12, P less than 0.02, and 0.54 +/- 0.14 mumols/ml, P less than 0.005, respectively). Myocardial production of 14CO2 showed that during control 9 +/- 10% of exogenous glucose was oxidized immediately upon extraction. Despite a significant increase in the amount of exogenous glucose oxidized with level II hyperglycemia, it represented only 32 +/- 10% of the glucose extracted. [13C]Lactate analysis showed that the myocardium was releasing lactate; during control 40 +/- 30% of this lactate was derived from exogenous glucose and during hyperglycemia this value increased to 97 +/- 37% (P less than 0.005). Thus, these data show that during short-term hyperglycemia, myocardial glucose extraction is enhanced. However, despite increases in exogenous glucose oxidation and the contribution of exogenous glucose to lactate release, the majority of the extracted glucose (i.e., 57%) is probably stored as glycogen.

Acetates↗
PubMed1989

Inhibition of endogenous lactate turnover with lactate infusion in humans.

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-14C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

Carbon Radioisotopes↗
PubMed1988

A model for measurement of lactate disappearance with isotopic tracers in the steady state.

1. The irreversible disappearance of lactate carbon from the body (RdL) is commonly calculated from data obtained with a continuous infusion of isotopically labelled lactate tracer. The tracer infusion rate divided by the steady-state lactate specific radioactivity in blood is taken to give the rate of lactate disappearance. 2. Measurement of lactate disappearance is complicated by the fact that it is reversibly converted into pyruvate as well as being irreversibly removed from the system. 3. We analysed a four-compartment model of lactate metabolism, representing blood lactate, tissue lactate and pyruvate carbon pools. 4. The standard method of calculating RdL from the lactate tracer infusion rate divided by the specific radioactivity of lactate was not validated. 5. We found that RdL can be calculated from the infusion rate and the pyruvate specific radioactivity, multiplied by the fraction of the total carbon flow out of pyruvate that goes to lactate. 6. Therefore, if almost all of the pyruvate carbon flows back to lactate, then RdL approaches the tracer infusion rate divided by the pyruvate specific radioactivity. On the other hand, if the rate of oxidation is large in relation to the rate of pyruvate conversion into lactate, than RdL is overestimated when calculated from the pyruvate specific radioactivity. 7. Calculation of RdL with the arterial lactate specific radioactivity results in an underestimate of the true RdL.

Animals↗
PubMed1988

Glucose and lactate interrelations during moderate-intensity exercise in humans.

To evaluate circulating lactate and glucose kinetics during moderate-intensity exercise, we studied ten healthy endurance-trained men (aged 25 +/- 6 years) during 30 to 50 minutes of supine cycle ergometer exercise at 43% +/- 5% of maximal oxygen consumption (VO2 max) using isotopic tracer techniques. Seven subjects received [U-13C]-lactate and [6-14C]-glucose, and three received [1-14C]-lactate and [U-13C]-glucose. Arterial glucose and lactate concentrations were 94.0 +/- 4.1 and 5.66 +/- 0.87 mg/dL at rest, and 95.7 +/- 3.4 and 8.38 +/- 3.87 mg/dL, respectively, after 25 minutes of exercise. The rate of glucose disappearance (RdG) increased from 2.41 +/- 0.40 at rest to 3.38 +/- 0.77 mg x kg-1 x min-1 during exercise, compared with the much larger rise in the rate of lactate appearance (RaL), which increased from 1.25 +/- 0.20 to 3.47 +/- 0.79 mg x kg-1 x min-1. During exercise RaL was 103% of RdG, compared with only 52% at rest. The rate at which the blood was cleared of lactate increased from 22.7 +/- 2.2 at rest to 44.2 +/- 11.2 ml x kg-1 x min-1 after 25 minutes of exercise. From secondary labeling of lactate with glucose carbons, the rate of glucose conversion to lactate was estimated to be 0.65 +/- 0.16 mg x kg-1 x min-1 during exercise. Twenty percent of the glucose utilization went to lactate formation during exercise, and 20% of the blood lactate appearance came from blood glucose, with the balance presumably coming from muscle glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Measuring tracee turnover from tracer specific activity in the steady state.

When a substrate appears in and disappears from an unmeasured (tissue) compartment, the proper sites for tracer infusion and sampling to measure tracee turnover become controversial. We analyze a three-compartment model representing arterial blood, tissue, and venous blood. The desired quantity, tracee turnover, is the ratio of the steady-state infusion rate to tissue specific activity. However, specific activity in the tissue compartment is unknown. We assume infusion of tracer into the arterial pool at a constant rate and consider sampling of specific activity of either blood compartment in the steady state. We obtain estimates of tissue specific activity from measurement of concentrations of tracer and tracee in blood samples in two extreme cases. In case I, tracee is assumed to appear in the venous compartment but to disappear from the tissue pool. Then tissue specific activity is equal to arterial specific activity. In case II, both appearance and disappearance are from the tissue pool. Tissue specific activity is then less than arterial or venous specific activity. We give formulas for the difference in each case. We discuss the relationship of our models to actual tracer experiments and define physiological locations for our three compartments. Appearance of substrates is probably intermediate between our extreme cases. A numerical estimate of turnover for the substrate lactate in resting humans reveals an error bound of approximately 30%. We discuss sites of infusion and sampling consistent with our model, the effects of relaxing some of our modeling constraints, and experimental necessities for getting beyond the steady state.

Algorithms↗
PubMed1988

Blood glutathione oxidation during human exercise.

To examine the effects of increased O2 utilization on the glutathione antioxidant system in blood, eight moderately trained male volunteers were exercised to peak O2 consumption (VO2peak) and for 90 min at 65% of VO2peak on a cycle ergometer. Blood samples were taken during exercise, and for up to 4 days of recovery from submaximal exercise. During exercise to VO2peak, blood reduced glutathione (GSH) and total glutathione [GSH + oxidized glutathione (GSSG)] did not change significantly. Lactate (L), pyruvate (P), and L/P increased significantly from rest values (P less than 0.01). During prolonged submaximal exercise, GSH decreased 60% from control, and GSSG increased 100%. Total glutathione, glucose, pyruvate, and lactate concentrations and L/P did not change significantly during sustained exercise. During recovery, GSH and GSH/GSSG increased from exercise levels and significantly overshot preexercise levels, reaching maximum values after 3 days. Oxidation of GSH during submaximal exercise and its reduction in recovery suggest increased formation of active O2-. species in blood during physical exercise in moderately trained males.

Adult↗
PubMed1988

Induced lactacidemia does not affect postexercise O2 consumption.

To study the effects of circulatory occlusion on the time course and magnitude of postexercise O2 consumption (VO2) and blood lactate responses, nine male subjects were studied twice for 50 min on a cycle ergometer. On one occasion, leg blood flow was occluded with surgical thigh cuffs placed below the buttocks and inflated to 200 mmHg. The protocol consisted of a 10-min rest, 12 min of exercise at 40% peak O2 consumption (VO2 peak), and a 28-min resting recovery while respiratory gas exchange was determined breath by breath. Occlusion (OCC) spanned min 6-8 during the 12-min work bout and elicited mean blood lactate of 5.2 +/- 0.8 mM, which was 380% greater than control (CON). During 18 min of recovery, blood lactate after OCC remained significantly above CON values. VO2 was significantly lower during exercise with OCC compared with CON but was significantly higher during the 4 min of exercise after cuff release. VO2 was higher after OCC during the first 4 min of recovery but was not significantly different thereafter. Neither total recovery VO2 (gross recovery VO2 with no base-line subtraction) nor excess postexercise VO2 (net recovery VO2 above an asymptotic base line) was significantly different for OCC and CON conditions (13.71 +/- 0.45 vs. 13.44 +/- 0.61 liters and 4.93 +/- 0.26 vs. 4.17 +/- 0.35 liters, respectively). Manipulation of exercise blood lactate levels had no significant effect on the slow ("lactacid") component of the recovery VO2.

Energy Metabolism↗
PubMed1988

Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments.

The purpose of this study was to investigate myocardial substrate utilization during moderate intensity exercise in humans. Coronary sinus and arterial catheters were inserted in nine healthy trained male subjects (mean age, 25 +/- 6 (SD) years). Dual carbon-labeled isotopes were infused, and substrate oxidation was quantitated by measuring myocardial production of 14CO2. Supine cycle ergometer exercise was performed at 40% of the subject's maximal O2 uptake. With exercise there was a significant increase in the arterial lactate level (P less than 0.05). A highly significant positive correlation was observed between the lactate level and the isotopic lactate extraction (r = 0.93; P less than 0.001). The myocardial isotopic lactate uptake increased from 34.9 +/- 6.5 mumol/min at rest to 120.4 +/- 36.5 mumol/min at 5 min of exercise (P less than 0.005). The 14CO2 data demonstrated that 100.4 +/- 3.5% of the lactate extracted as determined by isotopic analysis underwent oxidative decarboxylation. Myocardial glucose uptake also increased significantly with exercise (P less than 0.04). The [14C]glucose data showed that only 26.0 +/- 8.5% of the glucose extracted underwent immediate oxidation at rest, and during exercise the percentage being oxidized increased to 52.6 +/- 7.3% (P less than 0.01). This study demonstrates for the first time in humans an increase in myocardial oxidation of exogenous glucose and lactate during moderate intensity exercise.

Adult↗
PubMed1987

Ventilatory control studied with circulatory occlusion during exercise recovery.

Mechanisms involved in the control of pulmonary ventilation were studied in seven male subjects following 6 min of exercise on a cycle ergometer at 98w. Circulation to the legs was occluded by thigh cuffs (27 kPa) during the last 15 s of exercise and the subsequent 4 min of recovery. Respiratory gas exchange and the tidal partial pressures of O2 and CO2 were measured breath-by-breath. The results were compared to control studies without occlusion. There was a significant increase in both systolic and diastolic blood pressures during occluded recovery. Following occlusion systolic pressure remained elevated while diastolic pressure returned to control values. Occlusion during recovery caused hyperventilation during the first 1.5 min after exercise as evidenced by significantly higher VE/VCO2, VE/VO2, PETO2, and lower PETCO2. Following the release of the cuffs PETCO2, VE, VCO2, VO2, and heart rate all increased significantly above control values, while PETO2 decreased. PETCO2 rose abruptly 14.5 +/- 0.9 s after the release of the cuffs. Marked increases in VE and heart rate were seen, and occurred 30.8 +/- 1.5 s and 12.8 +/- 1.3 s, respectively, after cuff release. The 16.3 +/- 1.4 s lag between the increase in PETCO2 and VE after occlusion suggests that the ventilatory response to a sudden load of hypercapnic blood is not mediated by a pulmonary chemoreceptor. Other receptors, probably the peripheral chemoreceptors, appear to be responsible for hypercapnic hyperventilation.

Blood Circulation↗
PubMed1986

Lactate extraction during net lactate release in legs of humans during exercise.

Lactate metabolism was studied in six normal males using a primed continuous infusion of lactate tracer during continuous graded supine cycle ergometer exercise. Subjects exercised at 49, 98, 147, and 196 W for 6 min at each work load. Blood was sampled from the brachial artery, the iliac vein, and the brachial vein. Arteriovenous differences were determined for chemical lactate concentration and L-[1-14C]-lactate. Tracer-measured lactate extraction was determined from the decrease in lactate radioactivity per volume of blood perfusing the tissue bed. Net lactate release was determined from the change in lactate concentration across the tissue bed. Total lactate release was taken as the sum of tracer-measured lactate extraction and net (chemical) release. At rest the arms and legs showed tracer-measured lactate extraction, as determined from the isotope extraction, despite net chemical release. Exercise elicited an increase in both net lactate release and tracer-measured lactate extraction by the legs. For the legs the total lactate release (net lactate release + tracer-measured lactate extraction) was roughly equal to twice the net lactate release under all conditions. The tracer-measured lactate extraction by the exercising legs was positively correlated to arterial lactate concentration (r = 0.81, P less than 0.001) at the lower two power outputs. The arms showed net lactate extraction during exercise, which was correlated to the arterial concentration (r = 0.86). The results demonstrate that exercising skeletal muscle extracts a significant amount of lactate during net lactate release and that the working skeletal muscle appears to be a major site of blood lactate removal during exercise.

Adult↗
PubMed1985

Ventilation studied with circulatory occlusion during two intensities of exercise.

Our purpose was to study the possible role of a pulmonary chemoreceptor in the control of ventilation during exercise. Respiratory gas exchange was measured breath-by-breath at two intensities of exercise with circulatory occlusion of the legs. Eight male subjects exercised on a cycle ergometer at 49 and 98 W for 12 min; circulation to the legs was occluded by thigh cuffs (26.7 kPa) for two min after six min of unoccluded exercise. PETCO2 and VO2 decreased and PETO2 increased significantly during occlusion at both workloads. Occlusion elicited marked hyperventilation, as evidenced by sharp increases in VE, VE/VCO2, and VE/VO2. A sudden sharp increase in PETCO2 was seen 12.3 +/- 0.5 and 6.5 +/- 1.2s after cuff release in all subjects during exercise at 49 and 98 W, respectively. At 49 W a post-occlusion inflection in VE was seen in 7 subjects 21.1 +/- 5.8s after the PETCO2 inflection. Three subjects showed an inflection in VE at 98 W 23.3 +/- 7.5 s after the PETCO2 inflection. There were significant increases in PETCO2, VO2, VCO2 and VE after cuff release. VE mirrored VCO2 better than VO2, post occlusion. On the basis of a significant lag time between inflections in PETCO2 and VE following cuff release, it is concluded that the influences of a pulmonary CO2 receptor were not seen.

Adult↗
PubMed1985

Systemic lactate kinetics during graded exercise in man.

To investigate the relationships between oxygen consumption (VO2) and the rates of systemic lactate appearance (Ra) and disappearance (Rd), six healthy males were studied at rest and during continuous graded exercise using a primed continuous infusion of lactate tracer. Subjects exercised for 6 min at 300, 600, 900, and 1,200 kg . m . min-1. L-(+)-[1-14C]lactate was infused intravenously, and arterial samples were drawn at rest and every 2 min throughout the exercise period. Ra and Rd were calculated using nonsteady-state equations. At rest Ra and Rd were 14.4 +/- 1.8 and 15.1 +/- 2.2 mumol . kg-1 . min-1, respectively. Near steady-state values were observed toward the end of the first two work loads. Ra and Rd values were 32.8 +/- 2.3 and 37.4 +/- 1.3 mumol . kg-1 . min-1 during min 5 and 6 at 300 kg . m . min-1 and were 59.1 +/- 2.6 and 55.4 +/- 2.3 mumol . kg-1 . min-1 during min 5 and 6 at 600 kg . m . min-1. Ra was significantly greater than Rd at both 900 and 1,200 kg . m . min-1. Ra and Rd averaged 145.4 +/- 10.5 and 110.2 +/- 5.6 mumol . kg-1 . min-1, respectively, during the last 2 min at 900 kg . m . min-1, and 309.4 +/- 20.8 and 169.7 +/- 10.6 mumol . kg-1 . min-1, respectively, at 1,200 kg . m . min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗