A dynamic nonlinear lumped parameter model for skeletal muscle circulation

A dynamic nonlinear lumped parameter model of the circulation of skeletal muscle for constant vasoactive state is presented. This model consists of four compartments that represent the large arteries, the arterioles, the capillaries and venules, and the veins, respectively. The first compartment consists of a linear compliance (C₁) and resistance (R₁). The third compartment possesses no compliance and is represented by a linear resistance (R₃). The second and fourth compartments each consist of a nonlinear pressure-volume relation, resulting in a pressure dependent compliance (C₂, C₄, respectively) and nonlinear resistance (R₂, R₄, respectively). The eleven model parameters were collected in a complementary way: they were partly obtained from a priori knowledge including, information at the microscopic level, and partly determined by means of an estimation algorithm. Estimated values of the compliances (in cm³·kPa⁻¹·100 g⁻¹, 1kPa=7.5 mmHg) and resistances (in kPa·s·cm⁻³·100 g) at an (arterial) inflow pressure of 10 kPa and a (venous) outflow pressure of 0 kPa were: C₁: 0.014; R₁: 6.6; C₂: 0.565; R₂: 84.6; R₃: 37.9; C₄: 1.044; R₄: 24.5. The model (with the nonlinear pressure-volume relations) is able to predict the static and dynamic instantaneous (i.e., for constant vasomotor tone) pressure-flow relation and the instantaneous zero flow pressure intercept. These phenomena are therefore not necessarily the result of the rheological properties of blood. The secondary or delayed dilatation upon a positive inflow pressure step (or negative step in venous pressure) is predicted by the model implying that delayed dilatation is not necessarily related to changes in vasomotor tone. Venous outflow delay, upon a positive inflow pressure step (starting from zero flow), is also predicted by the model.     

Effects of antidiuretic hormone,parathyroid hormone and glucagon on transepithelial voltage and resistance of the cortical and medullary thick ascending limb of Henle's loop of the mouse nephron

The effect of antidiuretic hormone (arginine vasopressin, AVP, 10⁻¹⁰mol.l⁻¹), parathyroid hormone (PTH, 10⁻⁸ mol.l⁻⁸) and glucagon (10⁻⁸ mol.l⁻¹) on the transepithelial potential difference (PD_te) and the transepithelial resistance (R_te) were tested in in vitro perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. When compared with mTAL segments (PD_te: 8.5±0.4 mV,n=16), cTAL segments displayed a high PD_te of 15.7±0.9 mV (n=11) at the beginning of perfusion experiments which reached a value of 9.4±0.6 mV (n =11) after 38±4 min perfusion. Simultaneously R_te increased significantly from 24±3 to 28±1 Ω cm² (n=11). When PTH, AVP or glucagon were added to the bath solution, PD_te increased with PTH from 10.3±0.8 to 15.2±0.8 mV (n=13), with AVP from 10.2±0.5 to 15.0±0.7 mV (n=24) and with glucagon from 11.3±1.9 to 15.3±2.1 mV (n=8). At the same time R_te decreased from 30±3 to 23±2 Ω cm², from 28±1 to 23±1 Ω cm² and from 23±2 to 18±2 Ω cm², respectively. In mTAL segments, AVP and glucagon increased PD_te from 8.4+0.5 to 13.5±0.9 mV (n=11) and from 8.8±0.6 to 12.8±0.6 mV (n=8) respectively, while R_te decreased significantly from 23±1 to 20±1 Ω cm² and from 27±3 to 21±3 Ω cm². PTH, on the other hand, had no effect on PD_te and R_te. Since the response to PTH appeared to be specific to cTAL segments, paired experiments were performed, in which AVP or glucagon were successively tested with PTH on cTAL and mTAL segments, to ascertain the specificity of the hormonal response. In cTAL segments, PTH and AVP increased the equivalent short-circuit current (I_sc=PD_te/R_te) by 82% and 86% respectively, while PTH and glucagon, in another series, increased I_sc by 95% and 81% respectively. In mTAL segments, I_sc was increased in the presence of AVP and glucagon by 88%, and 93% respectively, whereas PTH had no effect. These results indicate that Nacl reabsorption in cTAL segments is stimulated by AVP, PTH and glucagon and in mTAL segments by AVP and glucagon. The amplitude of the response to the hormones is similar in the two segments. The residual stimulation in cTAL segments, however, persists longer than in mTAL segments.     

Hydrogel basedin vivo reference electrode catheter

A hydrogel basedin vivo reference electrode catheter has been developed. A simple diffusion model of ion transport was applied to study chloride ion transport through polyhydroxyethylmethacrylate (pHEMA) membranes. Based on an experimentally derived effective diffusion coefficient of D_eff=4·04±0·5×10⁻⁸ cm²s⁻¹, a reference electrode catheter was fabricated featuring a dimensionally appropriate pHEMA porous liquid junction, a gelled Ringer's solution internal electrolyte compartment and a Ag/AgCl internal half cell. The reference electrode potential is not a function of pH from pH6 to pH9 and is linearly related to temperature by 0·33 m V^oC⁻¹. In animal trials, the intravascular catheter electrodes exhibit an average stability of ±0·92mV for 6–8h. Stability in blood can be attributed to the haemocompatibility and transport properties of pHEMA.     

Analysis of cardiac left-ventricular volume based on time warping averaging

The cardiac left-ventricular (LV) volume signal, obtained by acoustic quantification, is affected by noise and respiratory modulation, resulting in a large beat-to-beat variability that affects the computation of LV function indices. A new method is proposed to improve the evaluation of LV indices by applying a signal averaging technique based on dynamic time warping to consecutive LV volume waveforms. Volume signals obtained from ten normal young (NY) subjects (mean age±SD: 25±5 years) were used to evaluate the performance of this algorithm. To evaluate its clinical utility, the effects of ageing and pharmacologically induced changes on LV function were assessed by studying, respectively, ten normal (N) adult subjects (age 64±8 years) and ten patients with dilated cardiomyopathy during a control and low-dose dobutamine (10 μg kg⁻¹ min⁻¹) study. Indices of LV function were highly consistent, with a variability of less than 8%, even when only 16 beats were averaged, independently of their selection inside the whole recording. When compared with beat-to-beat measures, the averaging of 16 beats significantly reduced (by more than 50%) the interbeat variability of all indexes. Expected alterations in both diastolic and systolic function were evidenced both with ageing (peak filling atrial contraction and ejection rates: from 275±77 ml s⁻¹, 76±30 ml s⁻¹, 230±70 ml s⁻¹, respectively, in NY, to 160±33 ml s⁻¹, 125±39 ml s⁻¹, 163±54 ml s⁻¹ in N) and with dobutamine (peak filling and ejection rates from 160±72 ml s⁻¹ and 183±86 ml s⁻¹ respectively, in control, to 253±75 ml s⁻¹ and 251±105 ml s⁻¹ with dobutamine). Signal averaging with time warping allows fast and improved assessment of LV function.     

Low edge damage container insert that adjusts intestinal forceps biopsies into Ussing chamber systems

 Ussing chamber experiments with human intestinal tissue are impeded by the small size of forceps biopsy specimens. Therefore, a miniaturized container insert featuring low edge damage was designed with an exposure area of only 0.05 cm². It allows measurement of short-circuit current (I _SC) and transmural resistance (R _t) on endoscopically obtained biopsy specimens, as well as alternating current impedance analysis and conductance scanning. Comparison with larger specimens mounted in a conventional Ussing chamber without the insert (exposure area 0.54 cm²) was made using rat jejunum and rectum. No differences in I _SC, R _t, or secretory response were found, indicating proper sealing and prevention of edge damage, as well as tissue viability in the container system. If biopsy samples obtained from human rectum were mounted in the insert, the local resistance near the edge was almost the same as the overall resistance (52.3 Ω·cm²). Epithelial and subepithelial resistances of human rectum were 43±1 Ω·cm² and 10±1 Ω·cm², respectively. In conclusion, we present a tool that allows reliable Ussing-type, impedance, and conductance scanning measurements to be made from intestinal biopsy specimens. Received: 30 November 1998 / Received after revision: 18 January 1999 / Accepted: 18 February 1999     

A two-compartment model of systemic circulation: Influence of transmural pressure

To study the effect of changes in transmural pressure upon parameters of a two-compartment model of the systemic circulation, a right-heart bypass preparation in 7 dogs separated the venous return into splanchnic and non-splanchnic (termed peripheral, ) flows. Flows from these two channels drained by gravity into an external reservoir. Reservoir blood was returned by a pump to the pulmonary artery. Venous resistances (R_vs and R_vp), arterial resistances (R_as and R_ap), compliances (C_s and C_p) and upstream venous pressures (P_s and P_p) for the splanchnic and peripheral channels were calculated from the steady-state and transient volume shifts which occurred following rapid drops in venous pressure. These parameters were determined at cardiac outputs of 48, 64, 80, 96, and 112 ml·kg⁻¹·min⁻¹. Linear regressions were obtained for venous resistances and compliances against the upstream venous pressure for the associated channel and also for the arterial resistances, against mean arterial pressure (P_a). Over the range of upstream venous pressures and arterial pressure produced by the cardiac output variations, statistically significant dependencies were found for R_vs and C_s against P_s, C_p against P_p, and R_as against P_a The peripheral compartment resistances, R_vp and R_ap, did not display significant dependencies on transmural pressure. A computer simulation of the effects of cardiac output variations induced by volume loading substantiates the conclusions that the observed curvature of pressure—flow relationships is due to increasing splanchnic venous resistance with upstream splanchnic pressure while the observed linearity of volume—flow relationships is due to the offsetting effects of increasing venous resistances and decreasing compliances with increasing upstream venous pressure. Supported in part by NHLBI Grant HL20371.     

Critical power of knee extension exercises does not depend upon maximal strength

A possible dependence of critical power (CP) and the Y-intercept of the work/exhaustion time relationship (Y _intercept) on maximal muscular strength of the same muscle group has been studied in nine endurance-trained subjects, seven gymnasts, and seven weight-lifters. CP was calculated as being equal to the slope of the linear relationship between exhaustion time and the work performed at exhaustion on a knee extension ergometer. Y _intercept was equal to the intercept between this relationship and the work axis. The muscular strength of the knee was evaluated by measuring the torques exerted on a Biodex knee isokinetic dynamometer at four angular velocities: 0° · s⁻¹ (T₀), 90° · s⁻¹ (T₉₀), 180° · s⁻¹ (T₁₈₀) and 240° · s⁻¹ (T₂₄₀). The results of the present study do not support the hypothesis that CP depends upon maximal strength. Indeed, CP was not correlated with T₀, T₉₀, T₁₈₀ or T₂₄₀ (|r| < 0.01). Y _intercept was significantly and positively correlated only with T₉₀. Accepted: 1 November 1999     

Dynamics of the short-term regulation of arterial pressure: Frequency dependence and role of arterial compliance

The purpose of this study was to investigate the role of the interaction between peripheral resistance regulation and arterial compliance in the overall short-term regulation of mean arterial pressure. A nonlinear model previously proposed was linearised about control values of mean arterial pressure and cardiac output so that it could be reformulated in terms of transfer functions. The resulting pressure to pressure open-loop transfer function H(s) consists of a complex conjugate pair of poles (pertaining to the resistance regulating system) and a real pole (pertaining to the arterial system, 1/(R₀ C), R₀=control resistance). Such a structure suggests an interaction between the resistance regulation and the arterial compliance (C). Quantitative evaluation of this interaction was obtained by estimating the model parameters during partial vena cava occlusions in four cats. Using these parameters the time response of the open-loop control system to a pressure step was found to be underdamped and oscillatory in all four cats (damping factor ξ ranged from 0·20 to 0·66), the amplitude of oscillations depending on the value of ξ and on the relative amplitude of the arterial time constant (compliance and peripheral resistance) with respect to the time constant 1/(ξω_n). Bode diagrams of H(jω) showed that the resonance peak due to the resistance regulating system may not be detectable, either because of the relatively high value of ξ or because it is masked by the pole of the arterial system.     

Energy cost and mechanical efficiency of riding a four-wheeled, human-powered, recumbent vehicle

Oxygen consumption at steady state (V˙O ₂, l · min⁻¹) and mechanical power (W˙, W) were measured in five subjects riding a human-powered vehicle (HPV, the Karbyk, a four-wheeled recumbent cycle) on a flat concrete road at constant sub-maximal speeds. The external mechanical work spent per unit of distance (W, J · m⁻¹), as calculated from the ratio of W˙ to the speed (v, m · s⁻¹), was found to increase with the square of v: W˙=8.12+(0.262 ·v ²) (r=0.986, n=31), where the first term represents the mechanical energy wasted, over a unit of distance, against frictional forces (rolling resistance, R_r), and the second term (k · v ²) is the work performed, per unit distance, to overcome the air drag. The rolling coefficient (C_r, obtained dividing R_r by m · g, where m is the overall mass and g is the acceleration of gravity) amounted to [mean (SD)] 0.0084 (0.0008), that is about 60% higher than that of a racing bicycle. The drag coefficient was calculated from the measured values of k, air density (ρ) and frontal area (A) [C_x=k · (0.5 · A · ρ)⁻¹], and amounted to 1.067 (0.029), that is about 20% higher than that of a racing bicycle. The energy cost of riding the HPV (C_k, J · m⁻¹) was measured from the ratio of metabolic power above rest (net V˙O ₂, expressed in J · s⁻¹) to the speed (v, m · s⁻¹); the value of this parameter increased with the square of v, as described by: C_k=61.45 + (0.675 · v ²) (r=0.711, n=23). The net mechanical efficiency (η) was calculated from the ratio of W to C_k: over the investigated speed range this turned out to be 0.22 (0.021). Best performance times (BPTs) of a “typical”élite athlete riding the Karbyk were calculated over the distances of 1, 5 and 10 km: these were about 8% longer than the BPTs calculated, on the same subjects, when riding a conventional racing bicycle. Accepted: 7 August 2000     

Energy cost of front-crawl swimming at supra-maximal speeds and underwater torque in young swimmers

The energy cost of front-crawl swimming (C_s, kJ · m⁻¹) at maximal voluntary speeds over distances of 50, 100, 200 and 400 m, and the underwater torque (T′) were assessed in nine young swimmers (three males and six females; 12–17 years old). C_s was calculated from the ratio of the total metabolic energy (E _s, kJ) spent to the distance covered. E _s was estimated as the sum of the energy derived from alactic (AnAl), lactic (AnL) and aerobic (Aer) processes. In turn, AnL was obtained from the net increase of lactate concentration after exercise, AnAl was assumed to amount to 0.393 kJ · kg⁻¹ of body mass, and Aer was estimated from the maximal aerobic power of the subject. Maximal oxygen consumption was calculated by means of the back-extrapolation technique from the oxygen consumption kinetics recorded during recovery after a 400-m maximal trial. Underwater torque (T′, N · m), defined as the product of the force with which the feet of a subject lying horizontally in water tends to sink times the distance from the feet to the center of volume of the lungs, was determined by means of an underwater balance. C_s (kJ · m⁻¹) turned out to be a continuous function of the speed (v, m · s⁻¹) in both males (C_s=0.603 · 10^{0.228 v} , r ²=0.991; n=12) and females (C_s=0.360 · 10^{0.339 v} , r ²=0.919; n=24). A significant relationship was found between T′ and C_s at 1.2 m · s⁻¹; C_s=0.042T′ + 0.594, r=0.839, n=10, P < 0.05. On the contrary, no significant relationships were found between C_s and T′ at faster speeds (1.4 and 1.6 m · s⁻¹). This suggests that T′ is a determinant of C_s only at speeds comparable to that maintained by the subjects over the longest, 400-m distance [mean (SD) 1.20 (0.07) m · s⁻¹]. Accepted: 25 August 2000     

Rheology of rat basophilic leukemia cells

Rat basophilic leukemia (RBL) cells, decorated with IgE, have been shown to bind irreversibly to antigen-coated sub-strates. In this paper we measured RBL cell deformability and demonstrated that this irreversible binding is not due to a compliant cellular rheology of these cells. The rheological properties of RBL cells were assessed with single-cell micropipette aspiration. Small-sized (G₁/G₀ phase) cells were found to be more deformable than medium-sized (S phase) cells. No changes in cellular rheology were observed after binding of anti-dinitrophenol IgE to Fc_e receptors. Furthermore, cytoplasmic viscosity μ showed power-law dependence on mean shear rate , where μc is a characteristic viscosity at characteristic shear rate , andb is a material coefficient. All the cells exhibited similar dependence on shear rate (b≈0.5). When was set to 1 s⁻¹, μ_c, 560±40 and 490±10 Pa·s for G₁/G₀, S cells, and G₁/G₀ cells treated with the antibody, respectively. In general, RBL cells were much more rigid than normal neutrophils (μ_c = 130 ± 20 Pa · s,b ≈ 0.05). Thus the biochemistry of the adhesion molecules,not the cellular deformability of the cell, is the cause of the irreversibility of RBL cell adhesion under flow.     

Metabolic and cardiorespiratory responses to maximal intermittent knee isokinetic exercise in young healthy humans

There have been many studies on the effects of isokinetic exercise on muscle performance in training and rehabilitative programmes. On the other hand, the cardiovascular and metabolic responses elicited by this type of exercise have been poorly investigated. This study was specifically designed to describe the relationships, if any, between metabolic and cardiorespiratory responses and power output during maximal intermittent knee isokinetic exercise when a steady state is reached. A group of 18 healthy subjects (10 men and 8 women, age range 25–30 years) were requested to perform at maximal concentric isokinetic knee extensions/flexions 60° · s⁻¹ and 180° · s⁻¹ for 5 min, with a 5-s pause interposed between consecutive repetitions. The power output (W˙) was calculated; before and during the tasks heart rate (f _c) and arterial blood pressure (AP_a) were continuously monitored. Pulmonary ventilation (V˙ _E) and oxygen uptake (V˙O₂) were measured at the 4th and at the 5th min of exercise and blood lactate concentration at rest and at the 3rd min of recovery. From the 4th to the 5th min only a slight decrease in W˙ was observed, both at 60° · s⁻¹ and 180° · s⁻¹. The V˙O₂, V˙ _E, f _c and AP_a showed similar values in the last 2 min of exercise, suggesting that a steady state had been reached. The V˙O₂ increased linearly as a function of W˙, showing a significantly steeper slope at 60° · s⁻¹ than at 180° · s⁻¹. The f _c, in spite of a large interindividual variation, was linearly related to metabolic demand, and was not affected by angular velocity. Systolic and diastolic AP_a were not related either to V˙O₂ or to angular velocity. In conclusion it would appear that the metabolic response to maximal intermittent knee isokinetic exercise resembles that of dynamic exercise. Conversely, the cardiocirculatory responses would seem to reflect a relevant role of the isometric postural component, the importance of which should be carefully evaluated in each subject. Accepted: 21 September 1999     

Electrolyte transport across the rabbit caecum in vitro

Electrolyte transport across rabbit caecal epithelium was investigated in vitro using conventional shortcircuiting and radioisotope techniques. In standard saline the caecum exhibited a relatively high short-circuit current (I _sc=4.4 μEq · cm⁻² · h⁻¹) and conductance (6.43 mS · cm⁻²). Both sodium and chloride were absorbed (J _net ^Na =6.40 andJ _net ^Cl =3.40 μEq · cm⁻² · h⁻¹) and potassium was secreted (J _net ^K =−0.5 μEq · cm⁻² · h⁻¹). Removal of Na⁺ abolishedI _sc andJ _net ^Cl whereas removal of Cl⁻ reducedJ _net ^Na to 2.92 μEq · cm⁻² · h⁻¹ but did not alterI _sc. In HCO ₃ ⁻ free salines containing 10⁻⁴ M acetazolamideJ _net ^Cl was abolished andJ _net ^Na andI _sc were reduced to 2.3 and 2.5 μEq · cm⁻² · h⁻¹ respectively. A positive residual ion flux (∼ 1 μEq · cm⁻² · h⁻¹) was detected in standard and Cl⁻-free salines but not in Na⁺-free or HCO ₃ ⁻ buffers. Mucosal amiloride (10⁻³ M) decreased net Na⁺ and Cl⁻ absorption but did not decreaseI _sc. Mucosal DIDS (10⁻⁴ M) decreasedJ _net ^Cl while mucosal bumetanide (10⁻⁴ M) did not affect any of the measured parameters. Finally, addition of theophylline (8 mM) stimulated Cl⁻ secretion and increasedI _sc. It is concluded that net sodium absorption by caecal epithelia occurs by both electrogenic and electroneutral mechanisms whereas net chloride absorption occurs only by an electroneutral process. Coupling of the absorptive fluxes of Na⁺ and Cl⁻ may result from Na⁺/H⁺ and Cl⁻/HCO ₃ ⁻ antiport systems in this tissue. Finally, it is proposed that up to half of theI _sc is due to a Na⁺-dependent secretion of bicarbonate ion.     

Role of nitric oxide in regulation of systemic vascular resistance during and after cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is known to result in the abnormal production of vasoactive substances contributing to the changes in hemodynamics such as systemic vascular resistance (SVR) during and after CPB. Nitric oxide (NO) is an inflammation-mediated vasoactive substance that plays a role in the whole-body inflammatory response induced by CPB. We evaluated the role of NO in the regulation of SVR during and after CPB. Fifteen patients underwent open-heart surgery for valvular heart disease. The perfusate blood temperature of CPB was set to 34°C. The plasma levels of NO metabolites (NO ₂ ⁻ +NO ₃ ⁻ ), prostaglandin E₂ (PGE₂), bradykinin (BK), and systemic vascular resistance index (SVRI) were measured before CPB and 0, 12, and 24 h after CPB. The plasma level of NO metabolites increased gradually after CPB (pre-CPB, 26.3 ±4.4; 0h, 33.7±6.5; 12 h, 49.8±11.1; 24 h, 43.1±7.5 μM). SVRI decreased gradually after CPB (pre-CPB, 2361±364; 0h, 2048±216; 12 h, 1590±308; 24 h, 1727±435 dyne·s·cm⁻⁵·m²). There was a significant inverse correlation between SVRI and the plasma level of NO metabolites as a whole (r=−0.674,P<0.0001). No significant correlations were observed between SVRI and the other vasoactive substances PGE₂ and BK. These findings demonstrated that NO production increased gradually during and after CPB in association with the decrease in SVR. Part of this study was presented at the 2nd annual meeting of the Japan Society for Adaptation Medicine on February 27, 1998     

Effects of multiple stenoses and post-stenotic dilatation on non-Newtonian blood flow in small arteries

Fully-developed one-dimensional Casson flow through a single vessel of varying radius is proposed as a model of low Reynolds number blood flow in small stenosed coronary arteries. A formula for the resistance-to-flow ratio is derived, and results for yield stresses of τ₀=0, 0.005 and 0.01 Nm^-2, viscosities of μ=3.45×10⁻³, 4.00×10⁻³ and 4.55×10⁻³ Pa·s and fluxes of 2.73×10⁻⁶, ×10⁻⁵ and ×10⁻⁴ m³s⁻¹ are determined for a segment of 0.45 mm radius and 45 mm length, with 15 mm abnormalities at each end where the radius varies by up to ±0.225 mm. When τ₀=0.005 Nm^-2, μ=4×10⁻³ Pa·s and Q=1, the numerical values of the resistance-to-flow ratio vary from , when the maximum radii of the two abnormal segments are both 0.675 mm, to , when the minimum radii are both 0.225 mm. The resistance-to-flow ratio moves closer to unity as yield stress increases or as blood viscosity or flux decreases, and the magnitude of these alterations is greatest for yield stress and least for flux.     

Evidence of break-points in breathing pattern at the gas-exchange thresholds during incremental cycling in young, healthy subjects

The present study investigated whether ‘break-points’ in breathing pattern correspond to the first ( G_\textEX1 G_{{{\text{EX}}_{1} }} ) and second gas-exchange thresholds ( G_{\textEX 2} G_{{{\text{EX}}_{ 2} }} ) during incremental cycling. We used polynomial spline smoothing to detect accelerations and decelerations in pulmonary gas-exchange data, which provided an objective means of ‘break-point’ detection without assumption of the number and shape of said ‘break-points’. Twenty-eight recreational cyclists completed the study, with five individuals excluded from analyses due to low signal-to-noise ratios and/or high risk of ‘pseudo-threshold’ detection. In the remaining participants (n = 23), two separate and distinct accelerations in respiratory frequency (f _R) during incremental work were observed, both of which demonstrated trivial biases and reasonably small ±95% limits of agreement (LOA) for the G_\textEX1 G_{{{\text{EX}}_{1} }} (0.2 ± 3.0 ml O₂ kg⁻¹ min⁻¹) and G_{\textEX 2} G_{{{\text{EX}}_{ 2} }} (0.0 ± 2.4 ml O₂ kg⁻¹ min⁻¹), respectively. A plateau in tidal volume (V _T) data near the G_\textEX1 G_{{{\text{EX}}_{1} }} was identified in only 14 individuals, and yielded the most unsatisfactory mean bias ±LOA of all comparisons made (−0.4 ± 5.3 ml O₂ kg⁻¹ min⁻¹). Conversely, 18 individuals displayed V _T-plateau in close proximity to the G_{\textEX 2} G_{{{\text{EX}}_{ 2} }} evidenced by a mean bias ± LOA of 0.1 ± 3.1 ml O₂ kg⁻¹ min⁻¹. Our findings suggest that both accelerations in f _R correspond to the gas-exchange thresholds, and a plateau (or decline) in V _T at the G_{\textEX 2} G_{{{\text{EX}}_{ 2} }} is a common (but not universal) feature of the breathing pattern response to incremental cycling.     

The effect of acute aerobic exercise on pulse wave velocity and oxidative stress following postprandial hypertriglyceridemia in healthy men

Oxidative stress is postulated to be responsible for the postprandial impairments in vascular function. The purpose of this study was to measure pulse wave velocity (PWV) and markers of postprandial oxidative stress before and after an acute bout of moderate exercise. Ten trained male subjects (age 21.5 ± 2.5 years, VO₂ max 58.5 ± 7.1 ml kg⁻¹ min⁻¹) participated in a randomised crossover design: (1) high-fat meal alone (2) high-fat meal followed 2 h later by a bout of 1 h moderate (60% max HR) exercise. PWV was examined at baseline, 1, 2, 3, and 4 h postprandially. Blood Lipid hydroperoxides (LOOHs), Superoxide dismutase (SOD) and other biochemical markers were measured. PWV increased at 1 h (6.49 ± 2.1 m s⁻¹), 2 h (6.94 ± 2.4 m s⁻¹), 3 h (7.25 ± 2.1 m s⁻¹) and 4 h (7.41 ± 2.5 m s⁻¹) respectively, in the control trial (P < 0.05). There was no change in PWV at 3 h (5.36 ± 1.1 m s⁻¹) or 4 h (5.95 ± 2.3 m s⁻¹) post ingestion in the exercise trial (P > 0.05). LOOH levels decreased at 3 h post ingestion in the exercise trial compared to levels at 3 h (P < 0.05) in the control trial. SOD levels were lower at 3 h post ingestion in the control trial compared to 3 h in the exercise trial (0.52 ± 0.05 vs. 0.41 ± 0.1 units μl⁻¹; P < 0.05). These findings suggest that a single session of aerobic exercise can ameliorate the postprandial impairments in arterial function by possibly reducing oxidative stress levels.     

The effect of acute metabolic alkalosis on bicarbonate transport along the loop of Henle. The role of active transport processes and passive paracellular backflux

The loop of Henle (LOH) reabsorbs approximately 15% of filtered HCO ₃ ⁻ via a luminal Na⁺-H⁺ exchanger and H⁺ATPase. During acute metabolic alkalosis (AMA) induced by i.v. HCO ₃ ⁻ infusion, we have observed previously inhibition of LOH net HCO ₃ ⁻ reabsorption , which contributes to urinary elimination of the HCO ₃ ⁻ load and correction of the systemic alkalosis. To determine whether the activities of the Na⁺-H⁺ exchanger and/or H⁺-ATPase are reduced during AMA, two inhibitors believed to be sufficiently specific for each transporter were delivered by in vivo LOH microperfusion during AMA. AMA reduced LOH from 205.0±0.8 to 96.2±11.8 pmol · min⁻¹ (P<0.001). Luminal perfusion with bafilomycin A₁ (10⁻⁴ mol · l⁻¹) caused a further reduction in by 83% and ethylisopropylamiloride (EIPA; 5.10⁻⁴ mol · l⁻¹) completely abolished net HCO ₃ ⁻ reabsorption. The combination of bafilomycin A₁ and EIPA in the luminal perfusate was additive, resulting in net HCO ₃ ⁻ secretion (−66.6±20.8 pmol · min⁻¹;P<0.001) and abolished net fluid reabsorption (from 5.0±0.6 during AMA to 0.2±1.1 nl · min⁻¹;P<0.001). To establish whether HCO ₃ ⁻ secretion via luminal stilbenesensitive transport mechanism participates in LOH adaptation to AMA, we added diisothiocyanato-2,2′-stilbenedisulphonate (DIDS; 10⁻⁴ mol · l⁻¹) to the perfusate. No effect was found. However, when the same LOH were exposed to luminal DIDS for more than 10 min, the direction of net HCO ₃ ⁻ movement was reversed and net HCO ₃ ⁻ secretion occurred: changed from 90.6±8.8 to −91.9±34.1 pmol · min⁻¹;P<0.01, an effect that was not observed in the control state (undisturbed acid-base balance). Thus, during AMA, neither the luminal Na⁺-H⁺ exchanger nor the H⁺-ATPase are noticeably suppressed. However, pharmacological elimination of both transporters, as well as prolonged exposure of the tubular lumen to DIDS, induced net HCO ₃ ⁻ secretion. This secretory flux may reflect paracellular backflux due to the steeper blood to lumen HCO ₃ ⁻ concentration gradient that presumably prevails in AMA.     

Cycling on Earth, in space, on the Moon

The mechanical power for cycling (P_c) at constant ground speed (s), in the absence of wind on smooth hard terrain is the sum of the power dissipated against rolling resistance, gravity and air resistance: P_c=a · s + M · g · s · sin γ + b · s ³, where a and b are constants, M is the mass of the subject plus bike, g is the acceleration of gravity and γ is the angle of the terrain with the horizontal. The constant b depends upon the drag coefficient (C_d), the overall area projected on the frontal plane (A _f), and the air density (ρ_a): b=0.5 · C_d · A _f · ρa. In turn, ρ_a depends on air pressure (P _B) and temperature (T): ρ_a=ρ₀ · 0.359 · P _B · T ⁻¹, where ρ₀ is the air density at 760 mmHg (101.3 kPa) and 273 K. The metabolic power developed by the cyclist (Ė _c) is related to P_c:Ė _c=P_c·η⁻¹, where η is the mechanical efficiency of cycling. The experimental values of a, b and η are fairly well known so that, if the maximal metabolic power as a function of the performance time is known for a given cyclist, the following set of data can be individually calculated: (1) best performances over any given distance and for any given altitude above sea level, (2) the effects of posture and body size on maximal speeds, and (3) the maximal incline of the terrain that can be overcome at any given speed or coasting speed for any given downslope. The above set of information makes it possible also to calculate the characteristics of a “Twin Bikes System” (TBS) for preventing microgravity deconditioning during long-term space flight. The TBS consists of two bicycles that are mechanically coupled by a differential gearing, which move at the very same speed, but in the opposite sense, along the inner wall of a cylindrically shaped space module. The circular trajectories induce a centrifugal acceleration vector (a _c) oriented along the head-to-feet direction of each subject: a _c=v _t ² · r ⁻¹ where v _t is the tangential velocity and r the radius of gyration, which is equal to the inner radius of the space module. So, any desired value of a _c can be achieved by appropriately selecting v _t, wherefrom the mechanical and metabolic powers that the astronauts must generate can be readily calculated. Experiments performed in a ground-based human centrifuge have shown that the discomfort derived from the rotating environment is reasonably low and well tolerated. If the appropriate atmospheric pressure is provided, cycling on circular or elliptical tracks may be useful to reduce cardiovascular deconditioning that occurs due to the reduced gravity in permanently manned lunar bases. Indeed, on the curved parts of the path a cyclist will generate a horizontal outward acceleration: a _c=s ² · r ⁻¹, where s is the velocity along the track and r is the radius of curvature. To counterbalance a _c, the subject plus bike must lean inwards so that the vectorial sum of a _c plus the lunar gravity (g _L=1.62 m · s⁻²) is applied along a straight line that includes the centre of mass of the system and the point of wheel contact with the ground. For values of s from 10 to 20 m · s⁻¹ and r from 50 to 200 m, this vectorial sum ranges from 1.05 to 5.03 g _L (0.17–0.83 g). Accepted: 20 March 2000     

Plasma vasopressin,renin activity,and aldosterone responses to maximal exercise in active college females

Summary The effect of maximal treadmill exercise on plasma concentrations of vasopressin (AVP); renin activity (PRA); and aldosterone (ALDO) was studied in nine female college basketball players before and after a 5-month basketball season. Pre-season plasma AVP increased (p<0.05) from a pre-exercise concentration of 3.8±0.5 to 15.8±4.8 pg · ml⁻¹ following exercise. Post-season, the pre-exercise plasma AVP level averaged 1.5±0.5 pg · ml⁻¹ and increased to 16.7±5.9 pg · ml⁻¹ after the exercise test. PRA increased (p<0.05) from a pre-exercise value of 1.6±0.6 to 6.8±1.7 ngAI · ml⁻¹ · hr⁻¹ 5 min after the end of exercise during the pre-season test. In the post-season, the pre-exercise PRA was comparable (2.4±0.6 ngAI · ml⁻¹ · hr⁻¹), as was the elevation found after maximal exercise (8.3±1.9 ngAI · ml⁻¹ · hr⁻¹). Pre-season plasma ALDO increased (p<0.05) from 102.9±30.8 pg · ml⁻¹ in the pre-exercise period to 453.8±54.8 pg · ml⁻¹ after the exercise test. In the post-season the values were 108.9±19.4 and 365.9±64.4 pg · ml⁻¹, respectively. Thus, maximal exercise in females produced significant increases in plasma AVP, renin activity, and ALDO that are comparable to those reported previously for male subjects. Moreover, this response is remarkably reproducible as demonstrated by the results of the two tests performed 5 months apart.