Rise In VO2 Research Articles

Dynamics of PO2 and VO2 in resting and contracting rat spinotrapezius muscle.

This study examined changes in interstitial PO2, which allowed calculation of VO2 during periods of rest, muscle contraction and recovery using an in situ rat spinotrapezius muscle preparation. The PO2 was measured using phosphorescence quenching microscopy and the muscle VO2 was calculated as the rate of O2 disappearance during brief periods of muscle compression to stop blood flow with a supra-systolic pressure. The PO2 and VO2 measurements were made during "5s compression and 15s recovery" (CR) cycles. With all three stimulation frequencies, 1, 2 and 4Hz, the fall in interstitial PO2 and rise in VO2 from resting values occurred within the first 20s of contraction. The PO2 during contraction became lower as stimulation frequency increased from 1 to 4Hz. VO2 was higher at 2Hz than at 1Hz contraction. With cessation of stimulation, PO2 began increasing exponentially towards baseline values. After 1 and 2Hz contraction, the fall in muscle VO2 was delayed by one CR cycle and then exponentially decreased towards resting values. After 4Hz stimulation, VO2 increased for 2 cycles and then decreased. The post-contraction transients of PO2 and VO2 were not synchronous and had different time constants. With further analysis two distinct functional responses were identified across all stimulation frequencies having PO2 during contraction above or below 30mmHg. The corresponding VO2 responses were different - for "high" PO2, muscle VO2 reached high levels, while for the "low" PO2 data set muscle VO2 remained low. Recovery patterns were similar to those described above. In summary, local microscopic PO2 and VO2 were measured in resting and contracting muscle in situ and the post-contraction transients of PO2 and VO2 were all much slower than the onset transients.

Cardiac Response During Exercise in Adolescents with Chronic Fatigue

PURPOSE: To describe the cardiac response to exercise in order to elucidate pathophysiology of adolescent chronic fatigue. METHODS: We reviewed records of adolescents with minimum 6-month history (in accordance with 2015 Institute of Medicine diagnostic criteria for Systemic Exertion Intolerance Disease) of chronic fatigue who underwent maximal cardiopulmonary exercise between June 2012 and December 2014. Patients in whom fatigue was not the primary problem or those with another medical diagnosis were excluded. All patients performed an incremental exercise (1-minute steps) test on a cycle ergometer to voluntary exhaustion with breath-breath measurement of gas exchange to determine peak oxygen uptake (VO2). Cardiac output (Q) was measured by acetylene rebreathing at rest plus at 1-3 levels of light-moderate exercise, and regressed against VO2. Stroke volume was normalized for body surface area to give stroke volume index (SVI). Patients were classified as unfit if their predicted peak VO2 was <90% (Cooper et al., 1984), which cutoff eliminated height/weight differences between groups. RESULTS: Our study population comprised 312 subjects with mean (±SD) age 15.6±1.7 years (77% female); Hgb level 13.5±1.2, with lowest 10 g/dL; unfit 75% of males and 80% of females. Overall Q rose normally with a mean slope 6.06±2.29 L-min-1 per L-min-1 VO2. SVI of fit males (59 mL) was significantly higher than unfit males (47 mL) at 30-60 W (p= 0.018, t-test). There were no differences in Q–VO2 relationship or HR between fit and unfit males. In contrast, Q of an unfit female rose an average of 5.96 L-min-1, significantly higher than 5.26 L-min-1 in a fit female, per L-min-1 VO2 (p= 0.012). For a 1L-min-1 rise in VO2, HR of an unfit female rose an average of 70 bpm vs 61 bpm for a fit female (p= 0.002, RM-ANOVA). There were no significant differences in SVI between fit and unfit females. CONCLUSION: Most males and females with chronic fatigue are deconditioned and show the classical cardiovascular features thereof. However, a subset of adolescent males achieves SVI in light exercise similar to that reported in healthy subjects. Findings suggest there may be muscle alterations or perceptual differences in chronic fatigue. Sex differences also exist in the cardiovascular response to exercise, perhaps related to Hgb levels or O2 extraction.

Use of electromyogram telemetry to assess the behavioural and energetic responses of rainbow trout, Oncorhynchus mykiss (Walbaum) to transportation stress

Behavioural and energetic responses of domesticated rainbow trout Oncorhynchus mykiss (Walbaum) (mean fork length=440±45 mm) to a brief transportation episode were investigated. Fish implanted with radio transmitters measuring muscle activity (electromyogram; EMGi) were transported in a standard commercial shipping tank for 50 min by truck, and then allowed to recuperate for 48 h in stationary culture tanks. The EMGi telemetry data indicated that vigorous swimming activity occurred during transportation. Telemetry recordings also indicated that the fish's swimming activity returned to baseline levels within the 48 h period after transport. However, even beyond the 48 h resting period, the swimming performance (measured as critical speed and endurance) of transported fish was still impaired relative to non-transported controls (P<0.05). Respirometry measurements of fish taken after transportation indicated that oxygen consumption (Vo2) was significantly elevated. The rise in Vo2 of post-transport fish could be attributed to handling procedures, as well as the intense swimming behaviour observed during transportation. Therefore, the behavioural responses of fish during transportation produced physiological consequences that persisted long after the transportation event. This study demonstrates the potential for utilizing behavioural measures, in concert with biotelemetry technologies, as tools to assess the impacts of routine aquacultural procedures on the health and welfare of captive fish.

Effect of Acute Creatine Kinase Inhibition on Intracellular PO2 Kinetics in Isolated Single Myocytes

0596 PURPOSE: The purpose of this investigation was to study the effects of acute creatine kinase (CK) inhibition (CKi) on intracellular PO2 (PiO2) in Xenopus laevis isolated single myocytes during a bout of moderate intensity contractions. METHODS: 15 min after an initial control (CON) contraction trial (2-min, isometric tetanic contractions, 0.33 Hz frequency), CK was inhibited with 2 mM iodoacetamide (n = 7) and the cells were subjected to the identical contraction protocol. PiO2 was measured continuously via phosphorescence quenching techniques. In accordance with Fick's Law, the fall in PiO2 is proportional to the rise in VO2. RESULTS: There was a significantly greater (P <0.05) fall in PiO2 from resting values in CON (26.0 ± 2.2 mmHg) compared to CKi (17.8 ± 1.8 mmHg) which was proportional to the loss in peak tension seen with CKi suggestive of an unaltered aerobic cost of contractions between trials. The speed of the fall in PiO2 at contractions onset, assessed via the time to 63% of the overall PiO2 fall (i.e., mean response time [MRT]) was significantly faster (P <0.05) in the CKi compared to CON trial (CKi = 31.8 ± 5.5 s; CON = 49.3 ± 5.7). Similarly, the speed of the PiO2 recovery following contraction cessation was significantly faster (CKi MRT = 21.2 ± 4.1 s; CON MRT = 68.0 ± 3.2; P <0.001) in the CKi compared to the CON trial. CONCLUSIONS: As PiO2 fell more rapidly at contractions onset in the CKi trial compared to CON, these data suggest CK activity buffers temporally the initial [ATP]/[ADP] at the transition to an augmented energetic demand, thereby slowing the initial mitochondrial activation by mitigating the energetic control signal (i.e., [ADP], phosphorylation potential, etc.) between sites of ATP supply and demand. Support: NIH AR-40155, NIH 1 F32 AR-48461, Parker B. Francis foundation.

Altered Contraction Frequency Yet Unchanged Duty Cycle Does Not Affect Single Myocyte Intracellular PO2 Kinetics

0097 Single myocyte intracellular PO2 (PiO2) onset kinetics become more rapid as contraction frequency increases, whereas off-kinetics remain invariant. PURPOSE: This study examined whether cells subjected to electrical stimulation protocols consisting of altered contraction frequency but identical duty cycle would show differing kinetics for changes in PiO2, whether at the onset or cessation of contractions. METHODS: Single intact skeletal muscle cells (n = 11) were isolated from Xenopus lumbrical muscle, injected with an O2 sensitive porphyrin dye and stimulated electrically (200 ms trains, 70 Hz, 1 ms duration) to contract isometrically in a perfusion chamber with an initial PiO2 of ∼ 30 Torr. Cells were stimulated for 2 min at both a high frequency (HF) of 1 contraction every 2 s and a low frequency (LF) of 1 contraction every 4s in a randomized order with 15 min rest between trials. Contraction durations of 250 ms (HF) and 500 ms (LF) were utilized to maintain identical duty cycles. PiO2 was measured continuously throughout the protocol via phosphorescence quenching. The fall in PiO2 is proportional to the rise in VO2 in accordance with Fick's Law. RESULTS: Force production at the end of the stimulation protocol was significantly lower in HF compared to LF (56 ± 8.0 vs. 73 ± 7.0 % of initial). Initial resting PiO2 (HF: 33.7 ± 1.9 vs. LF: 31.4 ± 1.2 Torr), steady-state PiO2 following isometric contractions (HF: 8.8 ± 1.7 vs. LF: 11.1 ± 2.0 Torr) and PiO2 following recovery (HF: 30.3 ± 0.6 vs. LF: 29.3 ± 0.8 Torr) were all not significantly different (p>0.05) between trials. Mean response time (MRT), calculated as time to 63% of the difference between initial and final PiO2, was not different between treatments for either the on-response (HF: 48.7 ± 4.4 vs. LF: 52.5 ± 4.9 s) or off-response (HF: 107.9 ± 10.8 vs. LF: 116.9 ± 11.7 s). CONCLUSIONS: These data suggest that altered contraction frequency yet unchanged duty cycle does not affect either the speed or magnitude of the fall in PiO2 at contraction onset. Supported by NIH AR40155 and 1F32 AR48461. RAH and CAK are Parker B. Francis Fellows.

Thermogenic effects of sibutramine and its metabolites.

1. The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. 2. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg(-1) of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5-1.0 degrees C) in body temperature. 3. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). 4. Combined high, non-selective doses (20 mg kg(-1)) of the beta-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, beta1-adrenoceptor-selective (atenolol) or beta2-adrenoceptor-selective (ICI 118551) doses (1 mg kg(-1)). 5. The ganglionic blocking agent, chlorisondamine (15 mg kg(-1)), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the beta3-adrenoceptor-selective agonist BRL 35135. 6. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg(-1)) that had no effect on VO2 when injected individually. 7. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via beta3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent.

MUSCLE USE AND THE SLOW COMPONENT RISE IN OXYGEN UPTAKE

386 The ˙VO2 slow component represents an additional oxygen cost that is superimposed on the rapid initial phase of oxygen uptake during constant-load exercise. It has been suggested that a progressive increase in muscle recruitment during heavy exercise may be responsible for the˙VO2 slow component. The purpose of this study was to determine if muscle use increased from 3-15 minutes of cycling that elicited a slow component rise in ˙VO2. ˙VO2 and lactate responses to constant-load cycle rides above and below lactate threshold were obtained for four subjects. In addition, exercise-induced contrast shifts in magnetic resonance images were obtained following 3 and 15 minutes of cycling at both intensities to determine the percent of muscle volume activated. The low-intensity bout produced a small rise in ˙VO2 (136±77.43 ml) from minute 3 (1329.8±308.8 ml) to minute 15 (1465.8±306.6 ml). This was accompanied by a small increase (23.8±3.9% to 28.9±6.2%) in muscle use and lactate (.95±.40 mmol/l to 1.21±43 mmol/l). The high-intensity bout produced a larger rise in VO2(418.73±189.81 ml) from minute 3 (2488.67±379.5 ml) to minute 15(2907.40±430.70 ml). Accordingly, there was a larger increase in muscle use (42.3±6.5% to 52.0±6.4%) and lactate (1.46+21 mmol/l to 4.47+.73 mmol/l) during the same period. This evidence supports the notion that increased muscle recruitment during constant-load exercise may be responsible for the ˙VO2 slow component.

Effects of hypoxic hypoxia on O2 uptake and heart rate kinetics during heavy exercise.

It is unclear whether hypoxia alters the kinetics of O2 uptake (VO2) during heavy exercise [above the lactic acidosis threshold (LAT)] and how these alterations might be linked to the rise in blood lactate. Eight healthy volunteers performed transitions from unloaded cycling to the same absolute heavy work rate for 8 min while breathing one of three inspired O2 concentrations: 21% (room air), 15% (mild hypoxia), and 12% (moderate hypoxia). Breathing 12% O2 slowed the time constant but did not affect the amplitude of the primary rise in VO2 (period of first 2-3 min of exercise) and had no significant effect on either the time constant or the amplitude of the slow VO2 component (beginning 2-3 min into exercise). Baseline heart rate was elevated in proportion to the severity of the hypoxia, but the amplitude and kinetics of increase during exercise and in recovery were unaffected by level of inspired O2. We conclude that the predominant effect of hypoxia during heavy exercise is on the early energetics as a slowed time constant for VO2 and an additional anaerobic contribution. However, the sum total of the processes representing the slow component of VO2 is unaffected.

Effect of the slow-component rise in oxygen uptake on VO2max.

During constant-rate high-intensity (CRHI) exercise lasting longer than 3 min, VO2 has been reported to exceed VO2max measured with a traditional graded exercise test (GXT). This could be because VO2max was not achieved on the GXT or because the factors responsible for the slow-component rise in VO2 alter VO2max. The objective of this study was to test the hypothesis that the slow-component rise in VO2 measured during CRHI running leads to a total VO2 that exceeds VO2max measured during a running GXT. VO2max was determined in eight highly trained individuals using data collected from five grade-incremented, treadmill-running GXT. Each subject demonstrated a definitive plateau of VO2 as a function of exercise intensity. Three VO2max values based on different approaches for representing the VO2max plateau were obtained. Subjects also completed two exhaustive CRHI bouts of treadmill running lasting 7-13 min at speeds estimated from the ACSM equation to elicit an average of 99 +/- 5% VO2max. The mean (+/- SD) VO2peak determined during the CRHI runs (4.17 +/- 0.9 l.min-1) was not different form or less than the three VO2max values (4.19-4.32 +/- 0.09 l.min-1). We conclude that in highly trained individuals, the slow-component rise in VO2 during CRHI treadmill running does not lead to a total VO2 that exceeds the VO2max measured during a running graded exercise test.

Pressure Support Ventilation Attenuates the Cardiopulmonary Response to an Acute Increase in Oxygen Demand

Critically ill patients undergo interventions, such as chest physical therapy, that acutely increase metabolic rate. Previous observations revealed that chest physical therapy is accompanied by increases of 40 to 50% in oxygen consumption (Vo2) and 40% in minute ventilation contributes to the rise in Vo2 and its associated hemodynamic responses. This was done by increasing mandatory ventilatory support during the chest physical therapy session: In phase 1 the mandatory ventilation rate was increased by 35% and in phase 2 pressure support ventilation 15 cm h2O was added. In phase 1 (n = 12), the increase in mandatory rate did not attenuate the chest physical therapy induced rises in heart rate, arterial blood pressure and Vo2. The increase in minute ventilation when the mandatory rate was increased prevented a rise in PaCO2. In phase 2 (n = 15), no change in the increase in Vo2 with chest physical therapy was observed with the addition of pressure support. Yet the rises in heart rate and systemic and pulmonary artery pressures were attenuated, as was the increase in PaCO2. Respiratory rate did not increase as much with pressure support. There appears to be a role for pressure support ventilation in attenuating the pulmonary and hemodynamic responses to interventions that increase oxygen demand.

Skeletal muscle oxygenation during constant work rate exercise

We compared the slow rise in VO2 during heavy exercise (i.e., greater than lactic acidosis threshold (LAT)) with changes in muscle oxyhemoglobin+oxymyoglobin (O2Hb/O2Mb) saturation by reflectance near infrared spectroscopy. Ten subjects performed four 6-min cycle ergometer tests with two constant work rates less than and two greater than the LAT, equivalent to 20, 40, 65 and 75% peak VO2. During less than LAT exercise, O2Hb/O2Mb saturation decreased to a minimum by 2 min and then remained constant or rose slightly. For greater than LAT work rates, the initial fall in O2Hb/O2Mb saturation was greater the higher the work rate and continued to decrease with time after 3 min. Between minutes 3 and 6, the rate of decrease in O2Hb/O2Mb saturation correlated with the increase in VO2 (r = -0.69, P < 0.0001). These studies support the hypothesis that the slow rise in VO2 during heavy constant work rate exercise is associated with a progressive decline in O2Hb/O2Mb saturation in the contracting muscles themselves that may be facilitated by capillary oxyhemoglobin dissociation owing to tissue lactic acidosis (Bohr effect).

O2 uptake kinetics and the O2 deficit as related to exercise intensity and blood lactate

The dynamic responses of O2 uptake (VO2) to a range of constant power output levels were related to exercise intensity [as percent maximal VO2 and as below vs. above lactic acid threshold (LAT)] and to the associated end-exercise lactate in three groups of subjects: group I, untrained subjects performing leg cycle ergometer exercise; group II, the same subjects performing arm cycle exercise; and group III, trained cyclists performing leg cycle ergometer exercise. Responses were described by a double-exponential equation, with each component having an independent time delay, which reduced to a monoexponential description for moderate (below-LAT) exercise. When a second exponential component to the VO2 response was present, it did not become evident until approximately 80-100 s into exercise. An overall time constant (tau T, determined as O2 deficit for the total response divided by net end-exercise VO2) and a primary time constant (tau P, determined from the O2 deficit and the amplitude for the early primary VO2 response) were compared. The tau T rose with power output and end-exercise lactate levels, but tau P was virtually invariant, even at high end-exercise lactate levels. Moreover the gain of the primary exponential component (as delta VO2/delta W) was constant across power outputs and blood lactate levels, suggesting that the primary VO2 response reflects a linear system, even at higher power outputs. These results suggest that elevated end-exercise lactate is not associated with any discernible slowing of the primary rise in VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

O2 Uptake Kinetics in Response to Exercise: A Measure of Tissue Anaerobiosis in Heart Failure

Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.

Age-related changes in endotoxin sensitivity and the febrile response of newborn rabbits.

Thermoregulatory responses to pyrogens in the immediate newborn period have been reported suppressed or undeveloped. In this study we investigated these responses in the newborn rabbit. Endotoxin (Escherichia coli LPS) was injected intraperitoneally in rabbits at different doses on day 0 (day of delivery), 1 or 3 of life, each animal being used only once. Oxygen consumption (VO2) and colonic temperature (Tc) were measured continuously for up to 5 h following endotoxin administration. On all days, a thermogenic response of a similar pattern was seen. At a low dose of endotoxin, there was a monophasic rise in VO2 that reached a peak at 2 h, followed by a plateau phase lasting a further 2-3 h. At an intermediate dose the response was biphasic with an initial smaller peak after 45-60 min and a second more sustained peak developing by about 2 h. At a higher dose the depression between the two peaks became deeper and longer with the second peak becoming more delayed and weaker. As animals got older, the doses needed to produce this sequence increased. On day 0 the increased VO2 caused by endotoxin was not accompanied by an increase in Tc. By day 3, Tc rose with the increase in VO2. We conclude that rabbits on the day of delivery respond to endotoxin with an increase in VO2 and by day 3 this is accompanied by an increase in Tc. The pattern of VO2, changes from monophasic to biphasic with increasing doses of endotoxin and the sensitivity to endotoxin decreases over the first 3 days of life.

Effect of pedal rate on cardiorespiratory responses during continuous exercise

The role of cycle ergometer pedal rate on the gradual increase in ventilation (VE), heart rate (HR), and oxygen uptake (VO2) accompanying continuous submaximal exercise is unknown. To examine this problem, five trained males (VO2peak = 4.00 +/- 0.27 l.min-1) performed 45 min of moderate intensity (MI, 127 W) and high-moderate intensity (HMI, 166 W) cycle ergometry both at pedal rates of 60 rpm and 90 rpm. Power output and pedal rate had an additive effect on the overall mean responses for VE, HR, and VO2, producing significantly higher values as power output and pedal rate increased. During continuous exercise, VE, HR, and VO2 increased progressively from the 10th to the 45th minute for all tests. However, the rates of increase and factors modifying the VE, HR, and VO2 responses were different. HR increased during all exercise tests an average of 10.8% independent of power output and pedal rate. VE increased 7.4% during MI exercise and 10% during HMI exercise independent of pedal rate. Similar power output dependent responses were observed for rectal temperature (Tr) and blood lactate. VO2 increased 4.4% for MI and HMI exercise at 60 rpm, and 8.2% for the same power outputs at 90 rpm, respectively. Increases in Tr, the oxygen cost of pulmonary ventilation and fat oxidation, and lactate removal were estimated to account for only 31-36% of the slow rise in VO2 for any single test. This suggests that 64-69% of the rise in VO2 was due to factors related to muscle use.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory and metabolic responses to acute hyperoxia in newborns.

Hyperoxia has previously been found to increase metabolic rate (oxygen consumption [VO2] and CO2 production [VCO2]) in newborn mammals. We asked whether the same occurs in the newborn infant. Breathing pattern was measured in 25 full-term infants, 1 to 2 days of age, from the spirometric record obtained with a pneumotachograph attached to a face mask. Concentrations of O2 and CO2 were continuously measured at the mouth; VO2 and VCO2 were computed as the product of VE and the difference between inspired and expired concentration of the respective gases, 5 min of air (FIO2 = 0.21) and 5 min of O2 (FIO2 = 1). A bias flow through the mask and pneumotachograph delivered the inspired gas and eliminated the effects of the instrumental dead space. In neither case did measurements at 1 min significantly differ from those taken at 5 min. In hyperoxia VE increased in 22 of the 25 infants, in average +18% (p less than 0.001, paired two-tailed t test). Because of a rise in tidal volume (+35%, p less than 0.001) and a decrease in breathing rate (-11%, p less than 0.005) alveolar ventilation (VA) increased by about 58% (p less than 0.001). VO2 and VCO2 increased by 25% and 17%, respectively (p less than 0.001). The rise in VO2 was too large to be explained by the greater respiratory work of the hyperventilation, whereas that of VCO2 was not large enough to fully explain the increase in VA. We conclude that in newborn humans, as in other newborn species, the normoxic metabolic rate seems to be limited by the availability of O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory and metabolic changes during high efficiency hemodialysis

Ventilatory and metabolic changes were measured in seven patients undergoing high efficiency hemodialysis using a cuprophane dialyzer and bicarbonate-containing dialysate. At an HCO3 concentration of 35 mEq/liter and a mean in vivo urea clearance of 3.6 ml/kg/min, hypoxemia was not detected during dialysis (PaO2 was 14.00 and 13.60 kPa before and during dialysis). The new findings, related to high efficiency bicarbonate dialysis, include a sustained rise in minute ventilation (VE, 6.1 to 6.8 liter/min, P less than 0.01), an increase in CO2 excretion (VCO2, 194 to 214 ml/min, P less than 0.05), and O2 consumption (VO2, 215 to 246 ml/min, P less than 0.05). The increment in VE and VCO2 was attributed to the high flux rate of bicarbonate while the rise in VO2 is likely the result of metabolic alkalosis. Arterial pH rose from 7.40 to 7.49 mm Hg and serum HCO3 increased from 23.8 to 29.2 mEq/liter, while pCO2 remained normal at 5.07 kPa throughout the study. The acid-base status of the blood changed from that of a metabolic acidosis to that of a respiratory acidosis across the dialyzer where the pH decreased from 7.47 to 7.41 and pCO2 rose from 5.31 to 7.72 kPa. These data indicate that a healthy ventilatory response is needed to excrete the excess CO2 generated during high efficiency bicarbonate hemodialysis. The significance and etiology of the elevated O2 consumption is undetermined.

The role of fitness on VO2 and VCO2 kinetics in response to proportional step increases in work rate

The purpose of this study was to determine the effect of fitness and work level on the O2 uptake and CO2 output kinetics when the increase in work rate step is adjusted to the subject's maximum work capacity. Nine normal male subjects performed progressive incremental cycle ergometer exercise tests in 3-min steps to their maximum tolerance. The work rate step size was selected so that the symptom-limited maximum work rate would be reached in four steps at 12 min in all subjects. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated breath by breath. For the group, the time (mean, SEM) to reach 75% of the 3-min response (T0.75) for VO2 increased significantly (P less than 0.01) at progressively higher work rate steps, being 53.3 (5.5) s, 63.5 (4.6) s, 79.5 (5.0) s, and 94.5 (5.8) s, respectively. In contrast, T0.75 for VCO2 did not change significantly [74.9 (7.4) s, 75.6 (5.0) s, 85.1 (5.3) s, and 89.4 (6.3) s, respectively]. VCO2 kinetics were slower than VO2 kinetics at the low fractions of the subjects' work capacities but were the same or faster at the high fractions because of the slowing of VO2 kinetics. The first step showed the fastest rise in VO2. While VO2 kinetics slowed at each step, they were faster at each fraction of the work capacity in the fitter subjects. The step pattern in VO2 disappeared at high work rates for the less fit subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermogenic effects of the antiglucocorticoid RU-486 in the rat: involvement of corticotropin-releasing factor and sympathetic activation of brown adipose tissue.

Acute injection (sc) of the antiglucocorticoid RU-486 (5-10 mg/kg) stimulated oxygen consumption (VO2) and brown adipose tissue (BAT) activity (mitochondrial GDP binding) in the rat. A peak effect was seen 60-80 min after injection. The rise in VO2 was prevented by prior injection of the beta-adrenergic antagonist propranolol, and the effect on BAT was abolished by surgical denervation of the sympathetic supply to the tissue. Central injection (cerebroventricular) of a much lower dose (3-8 micrograms/kg) of RU-486 also stimulated VO2, and this effect was inhibited by a CRF receptor antagonist [alpha-helical CRF-(9-41)]. Peripheral injection of RU-486 also elicited acute thermogenic responses in older (greater than 12 months) rats and in genetically obese (Zucker) rats. In lean animals, daily injection of RU-486 inhibited weight gain and stimulated BAT without affecting food intake. The thermogenic effects of RU-486 appear to be due to central stimulation of sympathetic outflow and may involve CRF release. The data support previous studies on the effects of adrenalectomy and CRF on thermogenesis in the rat.

Effects of Infection on Oxygen Consumption and Core Temperature in Experimental Thermal Injury

Oxygen consumption (VO2) and colonic temperature (Tc) were measured in groups of rats before and after 30% total body surface, full thickness burns. Some wounds were seeded with Pseudomonas aeruginosa or Staphylococcus epidermidis, and some seeded wounds were treated with Sulfamylon or Silvadene. Three groups became bacteremic (B) during the 2-3 week period of observation. At an ambient temperature (Ta) of 32 C, VO2 of the B group rose from 0.83 +/- 0.01 to 1.20 +/- 0.01 ml/hr/g (mean +/- S.E., p less than 0.001) versus 0.81 +/- 0.01 to 0.99 +/- 0.02 for nine nonbacteremic (NB) groups (p less than 0.001). Tc increased only in the B groups--from 36.8 +/- 0.1 to 37.7 +/- 0.1 C (p less than 0.001). In the second or third week postinjury, VO2 of the NB rats was reduced when Ta was increased to 34 C; Tc followed changes in Ta. Sulfamylon lowered VO2 of P. aeruginosa seeded, NB rats. The metabolic cost of wound contamination appeared to vary with bacterial strain. The metabolic effects of infection appear to be a continuum, beginning with a modest rise in VO2 and progressing to greater increases in VO2 and Tc with wound invasion and systemic infection.