Relation between the reaction cytochrome oxidase-oxygen and oxygen uptake in cells in vivo. The role of diffusion

Before reaching the oxidase located inside the cell on the mitochondrial membrane, oxygen may be slowed down by diffusion within the cytoplasm. Diffusion or enzymic activity may predominate and this is related to the size and morphology of the organism, the intracellular diffusion coefficient, and the K_m of the oxidizing terminal enzyme. This K_m may be apparently diminished by inhibitors. Different experimental situations can arise in some plants (where oxygen diffusion in bulk tissue is not important in comparison to that in cell): either oxygen diffusion is limiting, or diffusion and an enzymic reaction compete, or diffusion does not slow down the respiratory rate. A mathematical model relates the oxygen concentration in the external medium, to the rate of oxygen uptake at the oxygen cytochrome-oxidase reaction level.     

Relation between left ventricular cavity pressure and volume and systolic fiber stress and strain in the wall.

Pumping power as delivered by the heart is generated by the cells in the myocardial wall. In the present model study global left-ventricular pump function as expressed in terms of cavity pressure and volume is related to local wall tissue function as expressed in terms of myocardial fiber stress and strain. On the basis of earlier studies in our laboratory, it may be concluded that in the normal left ventricle muscle fiber stress and strain are homogeneously distributed. So, fiber stress and strain may be approximated by single values, being valid for the whole wall. When assuming rotational symmetry and homogeneity of mechanical load in the wall, the dimensionless ratio of muscle fiber stress (sigma f) to left-ventricular pressure (Plv) appears to depend mainly on the dimensionless ratio of cavity volume (Vlv) to wall volume (Vw) and is quite independent of other geometric parameters. A good (+/- 10%) and simple approximation of this relation is sigma f/Plv = 1 + 3 Vlv/Vw. Natural fiber strain is defined by ef = In (lf/lf,ref), where lf,ref indicates fiber length (lf) in a reference situation. Using the principle of conservation of energy for a change in ef, it holds delta ef = (1/3)delta In (1 + 3Vlv/Vw).     

Relationship between maximal oxygen uptake on different ergometers, lean arm volume and strength in paraplegic subjects

The present experiment was designed to study the importance of strength and muscle mass as factors limiting maximal oxygen uptake (V˙O_{2 max} ) in wheelchair subjects. Thirteen paraplegic subjects [mean age 29.8 (8.7) years] were studied during continuous incremental exercises until exhaustion on an arm-cranking ergometer (AC), a wheelchair ergometer (WE) and motor-driven treadmill (TM). Lean arm volume (LAV) was estimated using an anthropometric method based upon the measurement of various circumferences of the arm and forearm. Maximal strength (MVF) was measured while pushing on the rim of the wheelchair for three positions of the hand on the rim (−30°, 0° and +30°). The results indicate that paraplegic subjects reached a similar V˙O_{2 max} [1.23 (0.34) l · min⁻¹, 1.25 (0.38) l · min⁻¹, 1.22 (0.18) l · min⁻¹ for AC, TM and WE, respectively] and V˙O_{2 max} /body mass [19.7 (5.2) ml · min⁻¹ · kg⁻¹, 19.5 (6.14) ml · min⁻¹ · kg⁻¹, 19.18 (4.27) ml · min⁻¹ · kg⁻¹ for AC, TM and WE, respectively on the three ergometers. Maximal heart rate f _{c max} during the last minute of AC (173 (17) beats · min⁻¹], TM [168 (14) beats · min⁻¹], and WE [165 (16) beats · min⁻¹], were correlated, but f _{c max} was significantly higher for AC than for TM (P<0.03). There were significant correlations between MVF and LAV (P<0.001) and between the MVF data obtained at different angles of the hand on the rim [311.9 (90.1) N, 313.2 (81.2) N, 257.1 (71) N, at −30°, 0° and +30°, respectively]. There was no correlation between V˙O_{2 max} and LAV or MVF. The relatively low values of f _{c max} suggest that V˙O_{2 max} was, at least in part, limited by local aerobic factors instead of central cardiovascular factors. On the other hand, the lack of a significant correlation between V˙O_{2 max} and MVF or muscle mass was not in favour of muscle strength being the main factor limiting V˙O_{2 max} in our subjects. Accepted: 31 January 1997     

Relation between birth weight and blood pressure: longitudinal study of infants and children.

OBJECTIVE--To study the relation between birth weight and systolic blood pressure in infancy and early childhood. DESIGN--Longitudinal study of infants from birth to 4 years of age. SETTING--A middle class community in the Netherlands. PARTICIPANTS--476 Dutch infants born in 1980 to healthy women after uncomplicated pregnancies. MAIN OUTCOME MEASURES--Systolic blood pressure and body weight measured at birth and at 3 months and 4 years of age; the relation between systolic blood pressure and birth weight as estimated by multiple regression models that include current weight and previous blood pressure and control for gestational age, length at birth, and sex. RESULTS--Complete data were available on 392 infants. At 4 years of age the relation between blood pressure and birth weight appeared to be U shaped; low and high birthweight infants had raised blood pressure. Current weight and previous blood pressure were also positively associated with blood pressure at that age. Low birthweight infants (birth weight < 3100 g) had a greater gain in blood pressure and weight in early infancy. High birthweight infants (birth weight > or = 3700 g) had high blood pressure at birth, and weight and blood pressure tended to remain high thereafter. CONCLUSIONS--Even among normal infants there seem to be subgroups defined by birth weight in which blood pressure is regulated differently. Future investigations are needed to examine the physiological basis of these differences. Studies of correlates of adult disease related to birth weight should investigate mechanisms related to increased risk separately in infants of low and high birth weight.     

Scaling of maximal oxygen uptake by lower leg muscle volume in boys and men.

The aim of this study was to critically examine the influence of body size on maximal oxygen uptake (VO2 max) in boys and men using body mass (BM), estimated fat-free mass (FFM), and estimated lower leg muscle volume (Vol) as the separate scaling variables. VO2 max and an in vivo measurement of Vol were assessed in 15 boys and 14 men. The FFM was estimated after percentage body fat had been predicted from population-specific skinfold measurements. By using nonlinear allometric modeling, common body size exponents for BM, FFM, and Vol were calculated. The point estimates for the size exponent (95% confidence interval) from the separate allometric models were: BM 0.79 (0.53-1.06), FFM 1.00 (0.78-1.22), and Vol 0.64 (0.40-0.88). For the boys, substantial residual size correlations were observed for VO2 max/BM0.79 and VO2 max/FFM1.00, indicating that these variables did not correctly partition out the influence of body size. In contrast, scaling by Vol0.64 led to no residual size correlation in boys or men. Scaling by BM is confounded by heterogeneity of body composition and potentially substantial differences in the mass exponent between boys and men. The FFM is precluded as an index of involved musculature because Vol did not represent a constant proportion of FFM [Vol proportional, variantFFM1.45 (95% confidence interval, 1.13-1.77)] in the boys (unlike the men). We conclude that Vol, as an indicator of the involved muscle mass, is the most valid allometric denominator for the scaling of VO2 max in a sample of boys and men heterogeneous for body size and composition.     

Association between pulmonary function and peak oxygen uptake in elderly: the Generation 100 study

Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca2+ binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries. Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling. Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs. Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated. Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries. S100A4 immunohistochemistry was semi-quantitatively evaluated. Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter. Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors. These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining. Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries. Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay. Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells. Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients. As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.     

Relationship between resting ventilatory chemosensitivity and maximal oxygen uptake in moderate hypobaric hypoxia.

This study tested the hypothesis that the extent of the decrement in (.)Vo(2max) and the respiratory response seen during maximal exercise in moderate hypobaric hypoxia (H; simulated 2,500 m) is affected by the hypoxia ventilatory and hypercapnia ventilatory responses (HVR and HCVR, respectively). Twenty men (5 untrained subjects, 7 long distance runners, 8 middle distance runners) performed incremental exhaustive running tests in H and normobaric normoxia (N) condition. During the running test, (.)Vo(2), pulmonary ventilation (Ve) and arterial oxyhemoglobin saturation (Sa(O(2))) were measured, and in two ventilatory response tests performed during N, a rebreathing method was used to evaluate HVR and HCVR. Mean HVR and HCVR were 0.36 +/- 0.04 and 2.11 +/- 0.2 l.min(-1).mmHg(-1), respectively. HVR correlated significantly with the percent decrements in (.)Vo(2max) (%d(.)Vo(2max)), Sa(O(2)) [%dSa(O(2)) = (N-H).N(-1).100], and (.)Ve/(.)Vo(2) seen during H condition. By contrast, HCVR did not correlate with any of the variables tested. The increment in maximal Ve between H and N significantly correlated with %d(.)Vo(2max). Our findings suggest that O(2) chemosensitivity plays a significant role in determining the level of exercise hyperventilation during moderate hypoxia; thus, a higher O(2) chemosensitivity was associated with a smaller drop in (.)Vo(2max) and Sa(O(2)) under those conditions.     

Relation between birth weight at term and systolic blood pressure in adolescence.

OBJECTIVE--To examine whether birth weight is related to systolic blood pressure during adolescence. DESIGN--Retrospective (comparative) cohort study. The observers who traced and studied the subjects were unaware of their case-control status. SUBJECTS--330 subjects were born in Cardiff in 1975-7. Cases who were low birth weight at term (< 2500 g) were matched with controls of normal birth weight (3000-3800 g) at term. MAIN OUTCOME MEASURES--Systolic blood pressure measured by random zero sphygmomanometry in the subject''s right arm with the subject supine, corrected for size and age. RESULTS--The mean age at examination was 15.7 years. The mean systolic blood pressure of the cases was 105.8 mm Hg and of the controls 107.5 mm Hg. The corrected difference (95% confidence interval) in systolic blood pressure between the cases and controls was 1 mm Hg (-3 to +1 mm Hg; two tailed probability 0.33). CONCLUSION--Systolic blood pressure in adolescents of low birth weight is not significantly different from that of adolescents of normal birth weights.     

Gallbladder pressure, compliance, and hysteresis during cyclic volume change

The gallbladder has both storage and contractile properties, but is pressure-volume characteristics have not been fully described. We studied gallbladder pressure, compliance, stress relaxation, and the work performed during infusion-withdrawal of fixed volumes of bile at increments of base-line volume under halothane anesthesia in 13 dogs. Two cannulae were inserted in the gallbladder fundus: one for cyclic infusion-withdrawal of bile, and one for pressure monitoring. Following ligation of the cystic duct, the gallbladder was fully aspirated and then filled to successive predetermined base-line volumes (15, 20, 25, 30, or 35 mL). At each base-line volume, 5 mL of bile was infused and withdrawn at 2.47 mL/min. Studies were performed under basal conditions and with cholecystokinin octapeptide (CCK) infusion (10 or 30 ng.kg-1.h-1iv). Pressure was measured at base-line, after infusion, and after withdrawal. Compliance during infusion (delta V/delta P) was calculated for each cycle. Stress relaxation was defined as the difference between base-line pressure and any reduction in pressure after withdrawal. Hysteresis, the difference between work of infusion and work of withdrawal, was calculated. The results were such that base-line, end-infusion, and end-withdrawal pressures; work of infusion, work of withdrawal, and hysteresis; and stress relaxation all increased significantly with increases in the predetermined base-line volumes (p less than 0.001). Compliance decreased significantly (p less than 0.001) with increasing base-line volume. CCK at 10 ng.kg-1.h-1iv had no effect, but infusion of CCK at 30 ng.kg-1.h-1 significantly (p less than 0.05) increased pressure and work, decreased compliance, and increased stress relaxation compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure change in Africa: case study from Nigeria.

Studies of migrants and comparisons of rural versus urban communities are potentially informative study designs because they allow examination of genetically similar population subgroups exposed to diverse environmental conditions. These designs have been underused in Africa, where recent urbanization has created many situations in which nearby communities of common ethnicity and culture live under different social and economic circumstances. The International Study of Hypertension in Blacks (ICSHIB) conducted several overlapping surveys in Nigeria starting in 1993. These surveys were based primarily in the rural village of Idere and the urban community of Idikan, both inhabited by people defined ethnically as Oyo Yoruba and sharing a common language and culture. Survey teams collected standardized blood pressure and anthropometric measurements, and some study participants provided 24-hr urine samples and questionnaire data on psychosocial stress and social integration. Rural and urban groups differed substantially in blood pressure and related characteristics. Age-adjusted prevalence of hypertension (blood pressure > or = 140/90 mm Hg) for participants aged 25 years and older was 7-8% in Idere and 24-27% in Idikan. The distributions of overweight, sodium/potassium ratio, perceived stress, and social integration scores all contributed to lower hypertension risk in Idere. The effects and interactions of these identified risk factors remain poorly understood, even among people who share a common genetic background, similar diet, and many other lifestyle features. Nonetheless, the rural-urban distinction is sufficiently salient to engender a nearly threefold difference in hypertension prevalence. This disparity in disease prevalence demonstrates the sensitivity of human beings to the environmental determinants of disease and provides a sobering example of the difficulty in identifying subtle genetic effects, which can be easily overwhelmed by small differences in environmental exposures.     

Physiological background of the change point in VO2 and the slow component of oxygen uptake kinetics.

It is generally believed that oxygen uptake during incremental exercise--until VO2max, increases linearly with power output (see eg. Astrand & Rodahl, 1986). On the other hand, it is well established that the oxygen uptake reaches a steady state only during a low power output exercise, but during a high power output exercise, performed above the lactate threshold (LT), the oxygen uptake shows a continuous increase until the end of the exercise. This effect has been called the slow component of VO2 kinetics (Whipp & Wasserman, 1972). The presence of a slow component in VO2 kinetics implies that during an incremental exercise test, after the LT has been exceeded, the VO2 to power output relationship has to become curvilinear. Indeed, it has recently been shown that during the incremental exercise, the exceeding of the power output, at which blood lactate begins to accumulate (LT), causes a non-proportional increase in VO2 (Zoladz et al. 1995) which indicates a drop in muscle mechanical efficiency. The power output at which VO2 starts to rise non-proportionally to the power output has been called "the change point in VO2" (Zoladz et al. 1998). In this paper, the significance of the factors most likely involved in the physiological mechanism responsible for the change point in oxygen uptake (CP-VO2) and for the slow component of VO2 kinetics, including: increase of activation of additional muscle groups, intensification of the respiratory muscle activity, recruitment of type II muscle fibres, increase of muscle temperature, increase of the basal metabolic rate, lactate and hydrogen ion accumulation, proton leak through the inner mitochondrial membrane, slipping of the ATP synthase and a decrease in the cytosolic phosphorylation potential, are discussed. Finally, an original own model describing the sequence of events leading to the non-proportional increase of oxygen cost of work at a high exercise intensity is presented.     

Non-linear relationship between oxygen uptake and power output in the Astrand nomogram-old data revisited.

For the last decade there have been considerable discussion concerning the linearity / non-linearity of the oxygen uptake (V(O2)) - power output (W) relationship with strong experimental evidence of non-linearity provided mainly by breath-by-breath measurements. In this study, we attempted to answer the question whether the V(O2) - W relationship in the Astrand nomogram, as presented in the Textbook of Work Physiology, P.-O. Astrand et al. (2003), page 281, based on the Douglas bag method, is indeed linear, as stated by the authors before, or if a change point in V(O2), described by Zoladz et al. (1998) Eur J Appl Physiol 78: 369-377, can possibly be detected in those data. The V(O2) - W data were taken from the Astrand nomogram referenced above and from the Table 9.5 on page 282 in the same reference and tested for the presence of the change point in V(O2), using our two-phase model (see the reference above). In the first phase, a linear V(O2) - W relationship was assumed, whereas in the second one (above the so-called change point) an additional increase in V(O2) above the values expected from the linear model was allowed. It was found that in the data taken from the Astrand nomogram (data for men), as well as in the data taken from the Table 9.5, statistically significant change points in V(O2) were present at the power output of 150 W. The documentation of the presence of a change point in the V(O2) - W relationship in the Astrand data provides further evidence for the existence of a non-linearity in the V(O2) - W relationship in incremental exercise tests of humans, also in V(O2) data based upon the Douglas bag method.     

Polarographic measurement of oxygen uptake using lipoxygenase in reverse micelles

Lipoxygenase-catalyzed linoleic acid peroxidation was chosen as a model system to study the applicability of oxygraphy to monitor the oxygen uptake in organic solvents containing reverse micelles. Care was taken to control the oxygen back transfer from the atmosphere to the sample micellar solution, resulting in a significant improvement of electrode response. Under these conditions, lipoxygenase activity was linear up to 100 mug of enzyme. Given the quality of the calibration curve and the good correlation between lipoxygenase and ascorbate oxidase, the described technique is proposed as an alternative method for determining lipoxygenase activity in reverse micelles. The reliability of this technique was confirmed by the good agreement between polarography and classic spectrophotometry in kinetic studies. Preliminary experiments carried out on soybean cells solubilized in a Tween 85-isopropylpalmitate system demonstrated that a light-dependent oxygen uptake can be measured. The authors propose that the Clark-type electrode be employed to study both the activity of oxidasic enzymes in reverse micelles and cell viability and physiology in organic solvents.     

Relationship between muscle blood flow and oxygen uptake during exercise in endurance-trained and untrained men.

A recent study showed good correlation between regional blood flow (BF) and oxygen uptake (Vo(2)) 30 min after exhaustive exercise. The question that remains open is whether there is similar good correlation between BF and Vo(2) also during exercise. We reanalyzed our previous data from a study in which BF and Vo(2) was measured in different quadriceps femoris muscles in seven healthy endurance-trained and seven healthy untrained men at rest and during low-intensity intermittent static knee-extension exercise (Kalliokoski KK, Oikonen V, Takala TO, Sipila H, Knuuti J, and Nuutila P. Am J Physiol Endocrinol Metab 280: E1015-E1021, 2001). When the mean values of each muscle were considered, there was good correlation between BF and Vo(2) during exercise in both groups (r(2) = 0.82 in untrained and 0.97 in trained). However, when calculated individually, the correlations were poorer, and the mean correlation coefficient (r(2)) was significantly higher in the trained men (0.71 +/- 0.07 vs. 0.40 +/- 0.11, P = 0.03). These results suggest that there is large individual variation in matching BF to Vo(2) in human skeletal muscles during exercise, ranging from very poor to excellent. Furthermore, this matching seems to be better in the endurance-trained than in untrained men.