[Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome].

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

[Effect of antiviral therapy on the occurrence of hepatitis B-related hepatocellular carcinoma].

Clinically, hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. Hepatitis B virus infection is the main cause of hepatocellular carcinoma in China and it is a serious threat to people's health. Antiviral drugs such as nucleos(t)ide analogues and interferon can inhibit viral replication and liver fibrosis progression and reduce the occurrence of hepatitis B-related HCC. This article reviews the effects of different antiviral therapy on the occurrence of hepatitis B-related hepatocellular carcinoma in recent years.

[The intestinal microflora and cholestatic liver diseases].

Cholestatic liver diseases (CHD) refers to a kind of liver disease in which accumulation of excessive bile due to various causes from inside and outside of the liver blocks the formation, secretion and excretion of bile, and thereby induce the normal bile flow unable to enter the duodenum. During the occurrence and development of CHD, intestinal microflora plays an important role in regulating bile acid metabolism, and immune response. In addition, CHD affects the composition, abundance and function of intestinal microflora, which in turn affects the synthesis and metabolism of bile acids. Hence, bile acids being an important signaling molecule for the occurrence and development of CHD plays role in the pathophysiological processes through bile acid transporters and nuclear receptors, such as farnesoid receptors. This paper briefly introduces the relationship between intestinal microecology and cholestatic liver disease based on the interrelationship among bile acid, intestinal flora and cholestatic liver disease, with a view to provide assistance in the treatment of cholestatic liver disease.

[Host factors influencing the clinical outcome of chronic hepatitis B virus infection].

The clinical outcomes of chronic HBV infection are influenced by the interaction between virus, host and environmental factors. Several factors of host include age, sex, individual behavior, host genetic polymorphism and intestinal microflora, directly or indirectly affect the clinical outcome of chronic HBV infection. Therefore, in the management of chronic HBV infection, more attention need to be paid not only to antiviral therapy, but also to the impact of host factors in order to maximally improve the prognosis of patients.

Effect of TIEG1 on apoptosis and expression of Bcl-2/Bax and Pten in leukemic cell lines.

We examined the effect of transforming growth factor-b inducible early gene-1 (TIEG1) on the apoptosis of leukemic cell lines and expression of B-cell lymphoma 2 (Bcl-2) and phosphatase and tensin homolog (Pten). Four leukemic cell lines (HL-60, U937, Raji, and K562) were treated with 0, 1, 5, 10, and 20 ng/mL TIEG1, respectively. The cell growth inhibitory ratio was assessed using the MTT assay. An inhibitory curve was drawn, and half-maximal inhibitory concentration was calculated. Additionally, 1640 culture medium containing 10 ng/mL TIEG1 was used to culture leukemic cell lines for 0, 6, 12, 24, and 48 h. The apoptosis of each cell line at different time points was detected by flow cytometry. Total RNA was extracted before reverse transcription-polymerase chain reaction. The products of this reaction were analyzed by electrophoresis, and the expression of Bcl-2/Bcl-2-associated X protein (Bax) and Pten were detected. After treatment with TIEG1, proliferation of the 4 leukemic cell lines was inhibited both time- and dose-dependently. During apoptosis induction, the expression of Bcl-2 was decreased and the expressions of Bax and Pten were increased in the 4 leukemic cell lines induced by TIEG1 (P < 0.05). TIEG1 can inhibit the proliferation of leukemic cells and induce their apoptosis in a time- and dose-dependent manner. A close relationship exists between Bcl-2/Bax and Pten expression and cell apoptosis induced by TIEG1.

Dietary trans fatty acids combined with a marginal essential fatty acid status during the pre- and postnatal periods do not affect growth or brain fatty acids but may alter behavioral development in B6D2F(2) mice.

The objective of this study was to investigate whether dietary trans fatty acids (TFA) during the pre- and postnatal periods would exacerbate the effects of marginal essential fatty acid (EFA) status on growth, brain long-chain polyunsaturated fatty acids (LC-PUFA) and behavioral development in B6D2F(2) mice. Pregnant B6D2F(1) females were randomly assigned to one of the following three diets: marginal EFA plus 22% trans 18:1 (mEFA + TFA); marginal EFA (mEFA); and control (CON). The total 18:1 content in all diets was similar. The offspring were weaned and maintained on the same diets. Both the mEFA and mEFA + TFA groups had reduced growth and brain weight compared with CON, but did not differ from one another. As expected, the mEFA and mEFA + TFA groups had reduced docosahexaenoic acid [DHA; 22:6(n-3)]) and increased 22:5(n-6) concentrations in brain phosphatidylcholine (PC) and phosphatidylethanolamine (PE) compared with the CON group, but again did not differ from one another. Reversal learning in the T-water maze was significantly slower in the mEFA + TFA groups compared with the mEFA group and both were slower than the CON group. These findings illustrate that TFA combined with a marginal EFA status do not exacerbate the effects of marginal EFA status on growth or brain LC-PUFA. However, long-term effects of dietary TFA during the pre- and postnatal period on behavioral development and neural function should be investigated in future studies.

Early postnatal ethanol exposure has long-term effects on the performance of male rats in a delayed matching-to-place task in the Morris water maze.

BACKGROUND: There is concern that, in the absence of full-blown fetal alcohol syndrome, binge drinking during pregnancy might produce long-term cognitive deficits in offspring. Spatial working memory might be particularly vulnerable in this regard. This is the first study to address this issue in an animal model of binge exposure during the brain growth spurt using a delayed matching-to-place (DMTP) task in the Morris water maze. METHODS: Infant male rats were gastrostomized and reared artificially from postnatal days (PD) 5 to 18. From PD 6 to 9 they were fed either 6.5 g x kg(-1) x d (-1) ethanol (EtOH) in a binge exposure model (BAC 302 mg/dl) or an isocaloric maltose-dextrin solution (MD). The study included a third suckled control group (SC) that was reared normally. The rats were tested on a series of problems in the DMTP task, first as juveniles (PD 35) and then twice again as adults. Each problem included an initial search trial and a subsequent test trial. The first two phases of testing used delays of either 0 sec or 60 sec between these two trials. The third phase increased this delay to 60 sec and 2 hr. In addition, the rats were tested on a cued task in the water maze. RESULTS: EtOH rats were impaired relative to controls in their ability to relocate the hidden platform on the second trial, which followed the search trial. In Phases 1 and 2, there was no differential effect of ethanol on performance across the 0-sec and 60-sec delay conditions. However, EtOH rats were more affected by the longer 2-hr delay in Phase 3. There were no group differences on the search trial, in swimming speed, or cued-task performance. CONCLUSIONS: These findings establish that binge exposure to ethanol during the brain growth spurt results in a long-lasting impairment on the DMTP performance of rats in the water maze.

Effects of postnatal ethanol exposure on brain growth and lipid composition in n-3 fatty acid-deficient and -adequate rats.

The artificial rearing model was used to investigate the effects of short-term exposure to ethanol on growth and fatty acid composition of forebrain (FB) and cerebellum (CB) during the brain growth spurt in either n-3 fatty acid-adequate (AD) or n-3 deficient (DEF) rat pups. On postnatal day 5, offspring of female rats that had been fed AD or DEF diets from day 5 of life were assigned to three groups: members of two groups were gastrostomized and artificially fed formulas appropriate for their maternal history, and the third group (suckled control) was fostered to lactating dams of a similar dietary history. Half of the artificially reared pups in each dietary condition were fed ethanol in their formula (7% vol/vol) in one-quarter of their daily feedings, while the others received maltose-dextrin substituted isocalorically for ethanol. Blood alcohol concentrations did not differ between the dietary groups. FB weight on postnatal day 9 was lower in ethanol-exposed offspring in both dietary conditions. Brain fatty acid composition reflected dietary history in that, compared with AD pups, DEF pups had lower percentages of docosahexaenoic acid, higher percentages of 22:5n-6, and a higher n-6/n-3 fatty acid ratio. However, the effects of ethanol exposure were inconsistent, lowering the n-6/n-3 ratio in the phosphatidylethanolamine (PE) fraction in FB but not in CB, while increasing this ratio in the phosphatidylcholine (PC) fraction in FB of the DEF pups only. Thus, while ethanol had some effects on lipid composition, there was no difference between the dietary groups in their vulnerability to the effects of early short-term ethanol exposure on brain growth.

Effects of gamma-linolenic acid and docosahexaenoic acid in formulae on brain fatty acid composition in artificially reared rats.

This study evaluated the effects of dietary supplementation with gamma-linolenic acid (GLA, 18:3n-6) and docosahexaenoic acid (DHA, 22:6n-3) on the fatty acid composition of the neonatal brain in gastrostomized rat pups reared artificially from days 5-18. These pups were fed rat milk substitutes containing fats that provided 10% linoleic acid and 1% alpha-linolenic acid (% fatty acids) and, using a 2x3 factorial design, one of two levels of DHA (0.5 and 2.5%), and one of three levels of GLA (0.5, 1.0, and 3.0%). A seventh artificially reared group served as a reference group and was fed 0.5% DHA and 0.5% arachidonic acid (AA, 20:4n-6); these levels are within the range of those found in rat milk. The eighth group, the suckled control group, was reared by nursing dams fed a standard American Institute of Nutrition 93M chow. The fatty acid composition of the phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine/phosphatidylinositol membrane fractions of the forebrain on day 18 reflected the dietary composition in that high levels of dietary DHA resulted in increases in DHA but decreases in 22:4n-6 and 22:5n-6 in brain. High levels of GLA increased 22:4n-6 but, in contrast to previous findings with high levels of AA, did not decrease levels of DHA. These results suggest that dietary GLA, during development, differs from high dietary levels of AA in that it does not lead to reductions in brain DHA.

Neonatal dietary zinc deficiency in artificially reared rat pups retards behavioral development and interacts with essential fatty acid deficiency to alter liver and brain fatty acid composition.

The objective of this study was to investigate whether short-term zinc deficiency in the early neonatal period would exacerbate the effects of essential fatty acid (EFA) deficiency on liver and brain long-chain polyunsaturated fatty acid (LCPUFA) composition, as well as on behavioral development in artificially reared rat pups. Using a 2 x 2 factorial design, male Long-Evans rat pups were reared artificially from postnatal d 5 to 16; pups were fed through gastrostomy tubes with rat formula deficient in zinc and/or EFA. As expected, EFA deficiency significantly reduced levels of arachidonic acid [AA, 20:4(n-6)] and docosahexanoic acid [DHA, 22:6(n-3)] in liver phosphatidylcholine (PC) and brain phosphaditylethanolamine (PE), and increased 22:5(n-6) levels in liver and brain PC and PE. There were significant interactions between zinc and EFA in liver such that zinc deficiency reduced AA and DHA in the EFA-adequate groups, but significantly increased AA in the EFA-deficient groups. Contrary to the hypothesis, short-term zinc deficiency did not exacerbate the effects of EFA deficiency in liver phospholipids. In brain PE, a significant interaction between EFA and zinc was observed such that zinc deficiency increased 22:5(n-6) concentrations in EFA-adequate but not in EFA-deficient groups. Regardless of their EFA status, zinc-deficient rats were growth retarded and demonstrated deficits in locomotor skills. Possible effects of long-term zinc and EFA deficiency on brain function should be investigated in future studies.

Water maze performance is unaffected in artificially reared rats fed diets supplemented with arachidonic acid and docosahexaenoic acid.

Four groups of male Long-Evans rats were reared artificially from postnatal d 5 to 18 by being fed through a gastrostomy tube with rat milk substitutes containing oils providing 10% linoleic acid and 1% alpha-linolenic acid (g/100 g fat); with the use of a 2 x 2 design, they were fed one of two levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) (0.0 and 2.5 g/100 g of fatty acids). A fifth artificially reared group was fed a diet high in saturated fat, and a sixth group was reared by dams fed a standard AIN-93M diet. The pups were weaned onto modified AIN-93G diets, with a fat composition similar to that fed during the artificial rearing period. Behavioral testing was conducted between 6 and 9 wk of age; brain lipid composition was then assessed. Relative to the unsupplemented group (0.0 g/100 g AA and DHA), dietary supplementation resulted in a wide range of AA (84-103%) and particularly DHA (86-119%) levels in forebrain membrane phospholipids. AA supplementation increased AA levels and decreased DHA levels, and DHA supplementation increased DHA levels and decreased AA levels, with the magnitude of these effects dependent on the level of the other fatty acid. DHA levels were very low in the saturated fat group. The groups did not differ on the place or cued version of the Morris water-maze, but on a test of working memory, the saturated fat group was impaired relative to the suckled control group. Further correlational analyses in the artificially reared animals did not support a relationship between the wide range of DHA and AA levels in the forebrain and working-memory performance.

Long-chain polyunsaturated fatty acid levels in formulae influence deposition of docosahexaenoic acid and arachidonic acid in brain and red blood cells of artificially reared neonatal rats.

We studied the effects of dietary long-chain polyunsaturated fatty acids (PUFA) on the fatty acid composition of the brain and red blood cells in gastrostomized rat pups reared artificially from postnatal Days 5-18. These pups were fed rat milk substitutes in which the fat comprised 10% linoleic acid and 1% alpha-linolenic acid and, using a 3 x 3 factorial design, one of three levels of both arachidonic acid (AA) and docosahexaenoic acid (DHA) supplied as single cell microbial oils (0.0, 0.4 and 2.4% fatty acids). A tenth group was reared by nursing dams. The fatty acid composition of the phosphatidylethanolamine (PE) and phosphatidylserine/phosphatidylinositol (PS/PI) phospholipids in the brain and red blood cells on Day 18 reflected the dietary composition in that pups receiving long-chain supplementation of each had higher levels of the supplemented PUFA, but lower levels of the other, relative to unsupplemented groups. In contrast to these results, there were few changes in the brain in phosphatidylcholine (PC) phospholipids whereas, in the red blood cells, changes in PC were similar to those in PE and PS/PI. Regression analyses showed that DHA levels in the brain correlated more closely with those of the red blood cells than did AA levels. The results of this study indicate that, although supplementation of formula with AA or DHA during the period of rapid brain development in rats increases deposition of the long-chain PUFA in the developing tissues, each also affects the levels of the other.

Effects of Dietary n-3 Fatty Acid Deficiency on Morris Water-Maze Performance and Amphetamine-Induced Conditioned Place Preference in Rats.

In these studies we examined whether dietary n-3 fatty acid (FA) deficiency in adult male rats was associated with effects on performance in the Morris water-maze and with the development of a conditioned place preference to low (0.5 mg/kg) and high (2.0 mg/kg) doses of amphetamine. The male rats used in these studies had been raised for two generations on n-3 deficient diets, which produced an n-6: n-3 FA ratio in brain lipids three times that of animals fed an n-3 adequate diet. Although the two groups did not differ on learning the position of the hidden platform in the Morris water-maze, the n-3 deficient rats did show deficits on a subsequent working memory version of this task, and swam longer distances to reach a visible platform. There were no differences between the groups on the development of a conditioned place preference although, during the initial conditioning cycle, the increase in activity in response to the high dose of amphetamine was apparent only in the n-3 deficient group. These findings provide preliminary support for effects of n-3 FA deficiency on working memory, but not on motivational processes as measured by response to a drug reward.

Arachidonic acid offsets the effects on mouse brain and behavior of a diet with a low (n-6):(n-3) ratio and very high levels of docosahexaenoic acid.

This study investigated the effects of varying dietary levels of very long-chain polyunsaturated fatty acids on growth, brain fatty acid composition and behavior in mice. Five groups of pregnant and lactating B6D2F1 mice were fed diets with either a very high (n-6):(n-3) ratio of 49 [(n-3) deficient)], a normal ratio of 4.0 or a low ratio of 0.32. The (n-6) fatty acids (FA) were provided either entirely as linoleic acid (LA) or as LA in combination with arachidonic acid (ARA), and the (n-6):(n-3) ratios were adjusted by partial replacement of the (n-6) FA with docosahexaenoic acid (DHA). Offspring were maintained on these diets after weaning. The diets with the low (n-6): (n-3) ratio had no effect on the birth weights of the pups, but after 15 d resulted in a significant 12% reduction in body weights. This effect persisted to adulthood and was apparent in both brain and body weights unless ARA was substituted partially for LA as the source of (n-6) FA. There were significant effects of diet on brain fatty acid composition. Increasing levels of DHA in the diet increased brain DHA and decreased ARA, and there was also retroconversion of DHA in EPA in the mice fed high levels of DHA. Addition of ARA to the diet increased brain ARA, and, at high levels only, decreased DHA. There were no effects of this wide variation in dietary (n-6):(n-3) ratio on the ability of the mice to learn the place of the hidden platform in the Morris water maze. However, in both the cued and the place learning, the mice fed the low (n-6):(n-3) diet swam more slowly, unless ARA substituted partially for LA as the source of (n-6) FA. There were no effects of diet on activity in the spatial open field. These findings show that the effects of a diet with a low (n-6):(n-3) ratio and (n-3) FA provided as DHA, can be overcome if LA is partially replaced by ARA as the source of (n-6) FA.

Heart rate variability and fractal dimension during orthostatic challenges.

Heart rate variability (HRV) spectral analysis has been used as a tool for short-term assessment of parasympathetic (PNS) and sympathetic nervous system (SNS) control of heart rate. However, it has been suggested that the PNS and SNS indicators are superimposed on a broad-band noise spectrum in which the power spectral densities are inversely proportional to their frequency (1/f beta). In this study, we have used coarse-graining spectral analysis to extract the harmonic components for calculation of PNS and SNS indicators and to obtain the slope (beta) of the 1/f beta component to estimate fractal dimension (DF) of a trail of HRV. DF was regarded as an indicator of cardiovascular system complexity. Ten healthy young subjects (6 women and 4 men) were studied in supine rest and with sequential applications of four levels of lower body negative pressure (LBNP; -10, -20, -30, and -50 mmHg) and head-up tilt (HUT; 10, 20, 30, and 70 degrees). In the 20 tests, there were six occurrences of presyncopal symptoms that required the test to be terminated before the planned end point. At low levels of LBNP or HUT, arterial pulse pressure (PP) was not changed from rest, and calculated DF was very high (beta approximately 1.00). At the higher levels of LBNP and HUT, PP decreased. Coincident with this reduction in PP, PNS activity decreased, SNS activity increased, and DF was reduced, each with a significant linear relationship to the change in PP (PNS: r = 0.56; SNS: r = 0.57; DF: r = 0.70, P < 0.01). Each occurrence of presyncope was associated a low PNS indicator as well as DF < 2.50 (beta > or = 1.80). These data indicate that the cardiovascular system is operating at a reduced level of complexity and further suggest that reduced complexity might not be compatible with cardiovascular homeostasis.

Probing heart rate and blood pressure control mechanisms during graded levels of lower body negative pressure (LBNP).

Following space flight or head down tilt bed rest, cardiovascular deconditioning is often observed as a failure to maintain arterial blood pressure with symptoms of presyncope or syncope. LBNP can be used as a stressor of the cardiovascular system to observe the regulatory process. We have recently developed a new method to study cardiovascular control. Coarse graining spectral analysis (CGSA), allows simultaneous extraction of the harmonic components to evaluate sympathetic and parasympathetic nervous activities, and of the underlying complexity of the physiological response as given by the slope (beta) or fractal dimension (DF). The recognition that system complexity plays a major role in maintenance of cardiovascular stability is a relatively new concept. It was the purpose of the present study to examine the underlying complexity of heart rate and systolic blood pressure (SBP) variablities as indicated by the DF and power spectral analysis. Eight healthy men completed a test protocol of 20 min supine rest followed sequentially by 10 min at -5, -15, -25, -40, and -50 mmHg LBNP, and 10 min supine recovery. At rest, DF of R-R interval was 3.57 (beta = 1.56 +/- 0.12). There was a progressive decline in DF with LBNP, until at -50 mmHg, DF decreased to 1.2 (beta = 2.66 +/- 0.09). The DF for SBP was 1.3 (beta = 2.1 +/- 0.18) at rest, and was not significantly changed during LBNP. In the mid- and high-frequency ranges of the spectra, there was a moderately high degree of coherence between the variability in R-R interval and SBP. These findings indicate that short term SBP has a relatively low and unchanged complexity compared to heart rate. The changes in DF of heart rate variability were marked with increasing levels of LBNP. The results of this, and our previous study, indicate that a decline of DF to a critical level (near 1.4) is associated with orthostatic hypotension. These data show the utility of simple, non-invasive methods of data collection in conjunction with sophisticated data analysis techniques to point to possible mechanisms of orthostatic hypotension.

Frequency domain analysis of ventilation and gas exchange kinetics in hypoxic exercise.

The kinetics of O2 up-take (VO2), CO2 output (VCO2), ventilation (VE), and heart rate (HR) were studied during exercise in normoxia and hypoxia [inspired O2 fraction (FIO2) 0.14]. Eight male subjects each completed 6 on- and off-step transitions in work rate (WR) from low (25 W) to moderate (100-125 W) levels and a pseudorandom binary sequence (PRBS) exercise test in which WR was varied between the same WRs. Breath-by-breath data were linearly interpolated to yield 1-s values. After the first PRBS cycle had been omitted as a warm-up, five cycles were ensemble-averaged before frequency domain analysis by standard Fourier methods. The step data were fit by a two-component (three for HR) exponential model to estimate kinetic parameters. In the steady state of low and moderate WRs, each value of VO2, VCO2, VE, and HR was significantly greater during hypoxic than normoxic exercise (P less than 0.05) with the exception of VCO2 (low WR). Hypoxia slowed the kinetics of VO2 and HR in on- and off-step transitions and speeded up the kinetics of VCO2 and VE in the on-transition and of VE in the off-transition. Frequency domain analysis confined to the range of 0.003-0.019 Hz for the PRBS tests indicated reductions in amplitude and greater phase shifts in the hypoxic tests for VO2 and HR at specific frequencies, whereas amplitude tended to be greater with little change in phase shift for VCO2 and VE during hypoxic tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Time domain analysis of oxygen uptake during pseudorandom binary sequence exercise tests.

Pseudorandom binary sequence (PRBS) exercise tests involve repeated switching between two work rates (WR) according to a computer-generated pattern. This paper presents an approach to analysis of O2 uptake (VO2) in the time domain. First, the autocorrelation function (ACF) of the input WR was recognized to be a triangular-shaped pulse that can be taken to be equivalent to a ramp increase followed by a ramp decrease in WR. Then the cross-correlation function of the input (WR) and the output (VO2) was treated as if it were the response to a triangular-shaped pulse. The cross-correlation function was analyzed by fitting a linear summation of the ramp form of a two-component exponential function to this triangular pulse. VO2 responses of eight subjects were obtained from two different PRBS tests, as well as step changes in WR. The first PRBS test consisted of 15 units, each 30 s in duration. Its ACF had a base width of 60 s. The ramp increase-ramp decrease model fit the data throughout the range of response. The second PRBS test had 63 units, each 5 s in duration; thus its ACF base width was 10 s. Again, the ramp model fit adequately. The data from the second PRBS test could be fit by the impulse form of the two-component exponential equation, although the fit in the first 30 s tended to be poorer. The time constants of VO2 dynamics estimated from step and PRBS tests were not significantly different. PRBS tests can be analyzed in the time domain, and the indicators of system dynamics reflect physiological properties similar to those investigated during step changes in WR.

Alignment of ventilation and gas fraction for breath-by-breath respiratory gas exchange calculations in exercise.

The effects of correct alignment of the ventilation and fractional gas concentration during breath-by-breath calculation of oxygen uptake (VO2) have been examined during exercise in four subjects, at each of 50, 100, 150, and 200 W. Data were analyzed using lagtimes in the range of 200 to 400 msec to align ventilation with gas fraction. VO2 was markedly affected by lagtime. Calculated values of VO2 at 200 W ranged from 1953 +/- 55 (mean +/- SEM), to 2583 +/- 29, to 2843 +/- 28 ml.min-1 with lagtimes of 200, 310, and 400 msec, respectively. Mean values from a mixing box system did not differ significantly from the mean of the breath-by-breath data collection with a lagtime of 310 msec. Additional computations have shown that temperature correction can markedly affect calculated ventilatory volumes and N2 balance. VO2 was not changed because of the compensation from the calculated effects of changes in lung gas stores.