Linear-lumped-parameter modeling of pulmonary impedance in monkeys

Pulmonary impedance, Z_L, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linearlumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, D_r, between the computed network impedance and measured Z_L at all frequencies. Measured resistance, R_L, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (D_r∼19%). Networks consisting of two series RIC pathways in parallel resulted in a lower D_r (∼14%), but parameter values were difficult to interpret. Despite not modeling the decrease in R_L with frequency below 8 Hz, an airway wall compliance, C _aw , network in which the airways were separated into central and peripheral components resulted in an even lower D_r (∼11%). In addition, parameter values were easy to interpret, consistent among our “normal” monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that (1) networks containing both parallel pathways and C _aw are necessary to model Z_L over the entire frequency range (2–32 Hz), (2) the effect of C _aw is an important determinant of Z_L above 8 Hz, and (3) a six-parameter C _aw network with the ratio of C _aw to parenchymal compliance, C_p, fixed may prove useful in interpreting changes in Z_L induced by alterations in lung mechanics in monkeys.     

Differential Genetic Etiology of Reading Difficulties as a Function of IQ: An Update

In order to test the hypothesis that the genetic etiology of reading disability differs as a function of IQ, composite reading performance data from 308 pairs of identical (monozygotic, MZ) twins and 440 pairs of fraternal (dizygotic, DZ) twins (254 same-sex and 186 opposite-sex) in which at least one member of each pair was classified as reading-disabled were subjected to multiple regression analysis (DeFries and Fulker, Behav Genet 15:467–473, 1985; Acta Genet Med Gemellol 37:205–216, 1988). In the total sample, heritability of the group deficit in reading performance (h_g²) was .61 (±.06). However, results of fitting an extended regression model to reading performance and IQ data suggested that the genetic etiology of reading disability differs as a linear function of IQ (p ≤ .04). When the basic regression model was fitted separately to data from twin pairs with Wechsler (Examiner's manual: Wechsler intelligence scale for children—revised, 1974; Examiner's manual: Wechsler adult intelligence scale—revised, 1981) Full Scale IQ scores in the upper and lower 25% of the sample, resulting estimates of h_g² were .75 (±.12) and .50 (±.10), respectively (p ≤ .045). These results suggest that reading difficulties in children with a higher IQ are due substantially to genetic influences and may require intensive remediation efforts.     

Are the parameters of VO2, heart rate and muscle deoxygenation kinetics affected by serial moderate-intensity exercise transitions in a single day?

This study compared the parameter estimates of pulmonary oxygen uptake (VO_2p), heart rate (HR) and muscle deoxygenation (Δ[HHb]) kinetics when several moderate-intensity exercise transitions (MODs) were performed during a single visit versus several MODs performed during separate visits. Nine subjects (24 ± 5 years, mean ± SD) each completed two successive cycling MODs on six occasions (1-6A and 1-6B) from 20 W to a work rate corresponding to 80% estimated lactate threshold with 6 min recovery at 20 W. During one visit, subjects completed two series of three MODs (6A-F), separated by 20 min rest. VO_2p time constants (τVO_2p; 27 ± 10 s, 25 ± 12 s, 25 ± 11 s) were similar (p > 0.05) for MODs 1-6A, 1-6B and 6A-F, respectively. τVO_2p had reproducibility 95% confidence intervals (CI₉₅) of 8.3, 8.2, 4.7, 4.9 and 4.7 s when comparing single (1A vs. 2A), the average of two (1-2A vs. 3-4A), three (1-3A vs. 4-6A), four (1-2AB vs. 3-4AB) and six (1-3AB vs. 4-6AB) MODs, respectively. The effective Δ[HHb] response time (τ′Δ[HHb]) was unaffected across conditions (1-6A: 19 ± 2 s, 1-6B: 19 ± 3 s, 6A-F: 17 ± 4 s) with reproducibility CI₉₅ of 5.3, 4.5, 3.1, 2.9 and 3.3 s when a single, two, three, four and six MODs were compared, respectively. τHR was reduced in MODs 6A-F compared to 1-6A and 1-6B (23 ± 5 s, 25 ± 5 s, 27 ± 6 s, respectively). This study showed that parameter estimates of VO_2p, HR and Δ[HHb] kinetics are largely unaffected by data collection sequence, and the day-to-day reproducibility of τVO_2p and τ′Δ[HHb] estimates, as determined by the CI₉₅, was appreciably improved by averaging of at least three MODs.     

Bronchodilator effect on ventilatory,pulmonary gas exchange,and heart rate kinetics during high-intensity exercise in COPD

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and convective oxygen delivery during exercise, resulting in slower ventilatory, pulmonary gas exchange (PGE), and heart rate (HR) kinetics compared with normal. We reasoned that bronchodilators and the attendant reduction of operating lung volumes should accelerate ventilatory, PGE, and HR kinetics in the transition from rest to high-intensity exercise. Twelve clinically stable COPD patients undertook constant-work rate cycle testing at 75% of each individual’s maximum work capacity after receiving either combined nebulized bronchodilators (BD) or placebo (PL), randomly. Mean response time (MRT) and amplitude of slow component for oxygen uptake (V′O₂), carbon dioxide production (V′CO₂), ventilation (V′_E), and HR together with operating dynamic end-expiratory lung volume (EELV) were measured. Resting and exercise EELV decreased significantly by 0.38 L after BD compared with PL. After BD, V′O₂, V′CO₂, V′_E, and HR MRT accelerated (p < 0.05) by an average of 12, 22, 27, and 22 s, respectively (i.e., 15, 18, 22 and 27%, respectively). The slow component for V′O₂ declined by an average of 55 ml/min compared with PL. Speeded MRT for V′O₂ correlated with indices of reduced lung hyperinflation, such as resting EELV (r = −0.64, p = 0.025) and EELV at isotime (r = −0.77, p = 0.0032). The results confirm an important interaction between abnormal dynamic respiratory mechanics and indices of cardio-circulatory function in the rest-to-exercise transition in COPD patients.     

Influence of respiratory pressure support on hemodynamics and exercise tolerance in patients with COPD

Inspiratory pressure support (IPS) plus positive end-expiratory pressure (PEEP) ventilation might potentially interfere with the “central” hemodynamic adjustments to exercise in patients with chronic obstructive pulmonary disease (COPD). Twenty-one non- or mildly-hypoxemic males (FEV₁ = 40.1 ± 10.7% predicted) were randomly assigned to IPS (16 cmH₂O) + PEEP (5 cmH₂O) or spontaneous ventilation during constant-work rate (70–80% peak) exercise tests to the limit of tolerance (T _lim). Heart rate (HR), stroke volume (SV), and cardiac output (CO) were monitored by transthoracic cardioimpedance (Physioflow™, Manatec, France). Oxyhemoglobin saturation was assessed by pulse oximetry (SpO₂). At similar SpO₂, IPS₁₆ + PEEP₅ was associated with heterogeneous cardiovascular effects compared with the control trial. Therefore, 11 patients (Group A) showed stable or increased Δ “isotime” – rest SV [5 (0–29) mL], lower ΔHR but similar ΔCO. On the other hand, ΔSV [−10 (−15 to −3) mL] and ΔHR were both lower with IPS₁₆ + PEEP₅ in Group B (N = 10), thereby reducing ΔCO (p < 0.05). Group B showed higher resting lung volumes, and T _lim improved with IPS₁₆ + PEEP₅ only in Group A [51 (−60 to 486) vs. 115 (−210 to 909) s, respectively; p < 0.05]. We conclude that IPS₁₆ + PEEP₅ may improve SV and exercise tolerance in selected patients with advanced COPD. Impaired SV and CO responses, associated with a lack of enhancement in exercise capacity, were found in a sub-group of patients who were particularly hyperinflated at rest.     

Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO₂ difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO_2peak), and cardiac variables (thoracic bioimpedance)—cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)—at rest and during cycling exercise at 65% of VO_2peak. Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO_2peak and VO_2peak relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min⁻¹, p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM⁻¹ min⁻¹, p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min⁻¹, p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min⁻¹, p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min⁻¹ m⁻², p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min⁻¹, p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min⁻¹, p < 0.001, respectively) and a lower a-vO₂ difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml⁻¹, p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.     

Alternative strategies for exercise critical power estimation in patients with COPD

Exercise critical power (CP) has been shown to represent the highest sustainable work rate (WR) in patients with chronic obstructive pulmonary disease (COPD). Parameter estimation, however, depends on 4 high-intensity tests performed, on different days, to the limit of tolerance (T _lim). In order to establish a milder protocol that would be more suitable for disabled patients, we contrasted CP derived from 4, 3 and 2 tests (CP₄, CP₃ and CP₂) in 8 males with moderate COPD. In addition, CP was calculated from 2 single-day tests performed on an inverse sequence (CP_2AB and CP_2BA): CP values within 5 W from CP₄ were assumed as “clinically-acceptable” estimates. We found that [CP₄–CP₃] and [CP₄–CP₂] differences were within 5 W in 8 and 6 patients, respectively (95% confidence interval of the differences=−1.3 to 3.5 W and −11.5 to 6.5 W). There was a systematic decline on T _lim when an exercise bout was performed after a previous test on the same day (P<0.05). Consequently, substantial differences were found between CP₄ and any of the CP estimates obtained from single-day tests. In conclusion, clinically-acceptable estimates of CP can be obtained by using 3 or, in most circumstances, 2 constant WR tests in patients with moderate COPD—provided that they are not performed on the same day.     

Effect of obesity and metabolic syndrome on hypoxic vasodilation

This study was designed to test whether obese adults and adults with metabolic syndrome (MetSyn) exhibit altered hyperemic responses to hypoxia at rest and during forearm exercise when compared with lean controls. We hypothesized blood flow responses due to hypoxia would be lower in young obese subjects (n = 11, 24 ± 2 years, BMI 36 ± 2 kg m⁻²) and subjects with MetSyn (n = 8, 29 ± 3 years BMI 39 ± 2 kg m⁻²) when compared with lean adults (n = 13, 29 ± 2 years, BMI 24 ± 1 kg m⁻²). We measured forearm blood flow (FBF, Doppler Ultrasound) and arterial oxygen saturation (pulse oximetry) during rest and steady-state dynamic forearm exercise (20 contractions/min at 8 and 12 kg) under two conditions: normoxia (0.21 F_iO₂, ~98% S_aO₂) and hypoxia (~0.10 F_iO₂, 80% S_aO₂). Forearm vascular conductance (FVC) was calculated as FBF/mean arterial blood pressure. At rest, the percent change in FVC with hypoxia was greater in adults with MetSyn when compared with lean controls (p = 0.02); obese and lean adult responses were not statistically different. Exercise increased FVC from resting levels in all groups (p < 0.05). Hypoxia caused an additional increase in FVC (p < 0.05) that was not different between groups; responses to hypoxia were heterogeneous within and between groups. Reporting FVC responses as absolute or percent changes led to similar conclusions. These results suggest adults with MetSyn exhibit enhanced hypoxic vasodilation at rest. However, hypoxic responses during exercise in obese adults and adults with MetSyn were not statistically different when compared with lean adults. Individual hypoxic vasodilatory responses were variable, suggesting diversity in vascular control.     

Muscle deoxygenation to VO₂ relationship differs in young subjects with varying τVO₂

The relationship between the adjustment of muscle deoxygenation (∆[HHb]) and phase II VO_2p was examined in subjects presenting with a range of slow to fast VO_2p kinetics. Moderate intensity VO_2p and ∆[HHb] kinetics were examined in 37 young males (24 ± 4 years). VO_2p was measured breath-by-breath. Changes in ∆[HHb] of the vastus lateralis muscle were measured by near-infrared spectroscopy. VO_2p and ∆[HHb] response profiles were fit using a mono-exponential model, and scaled to a relative % of the response (0–100%). The ∆[HHb]/∆VO_2p ratio for each individual (reflecting the matching of O₂ distribution to O₂ utilization) was calculated as the average ∆[HHb]/∆VO_2p response from 20 to 120 s during the exercise on-transient. Subjects were grouped based on individual phase II VO_2p time-constant (τVO_2p): <21 s [very fast (VF)]; 21–30 s [fast (F)]; 31–40 s [moderate (M)]; >41 s [slow (S)]. The corresponding ∆[HHb]/∆VO_2p were 0.98 (VF), 1.05 (F), 1.09 (M), and 1.22 (S). The larger ∆[HHb]/∆VO_2p in the groups with slower VO_2p kinetics resulted in the ∆[HHb]/∆VO_2p displaying a transient “overshoot” relative to the subsequent steady state level, which was progressively reduced as τVO₂ became smaller (r = 0.91). When τVO_2p > ~20 s, the rate of adjustment of phase II VO_2p appears to be mainly constrained by the matching of local O₂ distribution to muscle VO₂. These data suggest that in subjects with “slower” VO₂ kinetics, the rate of adjustment of VO₂ may be constrained by O₂ availability within the active tissues related to the matching of microvascular O₂ distribution to muscle O₂ utilization.     

Sensitivity of local dynamic stability of over-ground walking to balance impairment due to galvanic vestibular stimulation

Impaired balance control during gait can be detected by local dynamic stability measures. For clinical applications, the use of a treadmill may be limiting. Therefore, the aim of this study was to test sensitivity of these stability measures collected during short episodes of over-ground walking by comparing normal to impaired balance control. Galvanic vestibular stimulation (GVS) was used to impair balance control in 12 healthy adults, while walking up and down a 10 m hallway. Trunk kinematics, collected by an inertial sensor, were divided into episodes of one stroll along the hallway. Local dynamic stability was quantified using short-term Lyapunov exponents (λ_s), and subjected to a bootstrap analysis to determine the effects of number of episodes analysed on precision and sensitivity of the measure. λ_s increased from 0.50 ± 0.06 to 0.56 ± 0.08 (p = 0.0045) when walking with GVS. With increasing number of episodes, coefficients of variation decreased from 10 ± 1.3% to 5 ± 0.7% and the number of p values >0.05 from 42 to 3.5%, indicating that both precision of estimates of λ_s and sensitivity to the effect of GVS increased. λ_s calculated over multiple episodes of over-ground walking appears to be a suitable measure to calculate local dynamic stability on group level.     

Probable reason why small strongyle EPG counts are returning “early” after ivermectin treatment of horses on a farm in Central Kentucky

Critical tests were carried out in 2008 in four yearling horses (H-2, H-4, H-10, and H-11) born and raised together on a farm (MC) in Central Kentucky. These horses were treated intraorally with ivermectin paste at the dose rate of 200 μg/kg. The main interest was to try and determine more precisely, from posttreatment (PT) worm count data, the current activity of ivermectin against small strongyles in a horse herd. These horses had been treated repeatedly with this compound and counts of small strongyle eggs per gram of feces (EPGs) of these parasites have been returning sooner than previously in field tests (Lyons et al. Parasitol Res 103:209–215, 2008a). Data from the four horses revealed that a total of 3,237 (nonfactored number) specimens of small strongyles was recovered from aliquot samples of feces passed PT and in the large intestinal contents at necropsy; all specimens were examined and identified. Thirteen species of adult small strongyles were recorded. Cylicocyclus (Cyc.) insigne was the predominant species. Three of the yearlings (H-2, H-4, and H-11) were necropsied at 6 days PT with ivermectin, and removals of small strongyles were: 50%, 80%, and 36% of fourth stages (L₄), respectively, and 100%, 99%, and 100% of adults, respectively. As indicated, the only incomplete removal of adults from the three horses was for H-4. They consisted of two species: (1) young Cyc. insigne (those passed in the feces were fully developed); removal of this species was 89% and (2) fully developed Cylicostephanus longibursatus; 99% were removed. The fourth yearling (H-10), necropsied at 25 days PT, harbored 19,150 adult small strongyles in the large intestinal contents. Most of the species were Cyc. insigne; all were fifth stage but not sexually mature. Comparing the percentage of adult small strongyles found at necropsy relative to the total number present (those passed in the feces and at necropsy), only 0% to 1% were in the contents of the large intestines of the three horses at 6 days PT but in 26% for horse H-10 at 25 days PT. As mentioned earlier, only a few adults were found in one horse and several L₄ in the three horses at necropsy at 6 days PT. Therefore, in horse H-10, most adults found at 25 days PT presumably developed from “young” specimens not removed by ivermectin. Thus, data from the present critical tests indicate the probable cause of the “early” return of small strongyle EPG values after ivermectin treatment in the horses in field tests on Farm MC. It seems this was the result of incomplete removal of luminal specimens (L₄ and possibly young adults), some of which matured and began laying eggs by about 4 weeks PT (Lyons et al. Parasitol Res 103:209–215, 2008a). The research also showed that ivermectin was highly effective on adult small strongyles. At necropsy, the following other species of parasites (adult) were found, but none was recovered from the feces. These were (n = number of horses infected): (1) ascarids (Parascaris equorum—n = 1), (2) tapeworms (Anoplocephala perfoliata—n = 4), and (3) pinworms (Oxyuris equi—n = 3). Immature (L₄) O. equi were present in two horses and removals were 0% in one horse and 39% in the other. Eyeworms (Thelazia lacrymalis) were found in one horse at necropsy. Even though a small number of horses were used in the present research, the commonality of their background made them ideal candidates as a group for this study. This aspect helps strengthen the validity of the interpretation of the findings.     

Lactate response to short term exercise with elevated starting levels

A model that describes the blood lactate concentration (BLC) dynamics [BLC(t)] of a Wingate Anaerobic Test (WAnT) as a function of (a) BLC at the start of exercise (BLC₀), (b) extra-vascular increase in lactate (A), (c) two corresponding velocity constants of appearance (k ₁) and disappearance (k ₂) of lactate into and out of the blood requires that BLC₀ is equal to resting BLC (BLC_rest). We developed a model that considers an elevated BLC₀. 19 males performed WAnTs with warm-ups increasing (p < 0.001) BLC₀. The goodness of each individual fit improved (p < 0.05) if the difference between BLC_rest and BLC₀ (ΔBLC) was higher than 1.0 mmol l⁻¹. All differences between old and new model (p < 0.05) in A, k ₁ and k ₂ were interrelated with and increased with ΔBLC (p < 0.05). The new model well describes BLC(t) and prevents substantial errors concerning lactate generation and dynamics if BLC₀ is elevated by more than 1.0 mmol l⁻¹.     

Contributions of neural tone to in vivo passive muscle--tendon unit biomechanical properties in a rat rotator cuff animal model

Passive viscoelastic properties of muscle–tendon units are key determinants of intra- and post-operative success. Atrophied, retracted, and stiff muscle–tendon units are technically challenging to manipulate and perform poorly after surgical repair. This study employs botulinum neurotoxin A (BoNT-A)-mediated inhibition of presynaptic acetylcholine release to examine in vivo neural contributions to soft-tissue biomechanical properties. In vivo load-relaxation and active muscle contractile force testing protocols were performed in the rat rotator cuff model. The passive properties were assessed using linear regression analysis and Fung’s quasi-linear viscoelastic (QLV) model. BoNT-A injected muscle–tendon units had a significant reduction in force of contraction (p = 0.001). When compared to saline injected controls, the BoNT-A significantly decreased parameter ‘A’ of the QLV model, which represents the linear elastic response (p = 0.032). The viscous properties in the BoNT-A treatment group were not significantly different from saline injected controls, as determined by comparison of QLV model parameters ‘C,’ ‘τ₁,’ and ‘τ₂.’ In conclusion, neural tone contributes significantly to muscle–tendon unit passive biomechanical properties. Pre-surgical treatment with BoNT-A may improve the rehabilitation of muscle by altering its passive elastic properties. Accordingly, pharmacological modulation of skeletal muscle stiffness with BoNT-A increases flexibility, potentially improving function. Chemical denervation with BoNT-A may also improve the manipulation of stiff and difficult to mobilize muscles during surgical procedures.     

Relevance of lower airway bacterial colonization, airway inflammation, and pulmonary function in the stable stage of chronic obstructive pulmonary disease

The objective of this investigation was to verify the hypothesis that the presence of lower airway bacterial colonization (LABC) can be a stimulating factor of airway inflammation, more frequent exacerbation, and impact on pulmonary function, independent of current tobacco smoking in the stable phase of chronic obstructive pulmonary disease (COPD). A total of 46 ex-smokers with moderate to severe COPD, 19 healthy non-smokers, and 17 ex-smokers without COPD were included in this study. Their sputum specimens were collected at the first baseline visit and at the second visit after a follow-up of one year. The samples were analyzed for bacterial growth by culture, and the levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The frequencies of exacerbations and pulmonary function were compared at visit 2. At visit 1, 37.0% (17/46) were found to have LABC with bacterial loads ≥10⁶ CFU/ml in their sputum specimens. Haemophilus influenzae was the predominant pathogenic organism isolated. IL-8, IL-6, and TNF-α in these patients’ sputum were significantly higher than those without LABC (p < 0.05). It was the presence of LABC that contributed to the significantly elevated IL-8 and IL-6 at the 1-year period (p < 0.05). LABC was also associated with significantly increased frequencies of exacerbations and declined forced expiratory volume in 1 s (FEV₁) (p < 0.05). LABC was documented in a subpopulation of stable COPD patients; it may be responsible for the deterioration of pulmonary function of COPD patients by promoting airway inflammation and/or increased frequency of exacerbations independently of tobacco smoking.     

Fibrinogen Beta-Chain -C148T Polymorphism is Associated with Increased Fibrinogen, C-Reactive Protein, and Interleukin-6 in Patients Undergoing Coronary Artery Bypass Grafting

The fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- and early postoperative levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) in 243 consecutive patients undergoing coronary artery bypass grafting (CABG) surgery. Plasma inflammatory markers were measured prior to and 5–7 days after surgery. The -C148T polymorphism was analyzed with the restriction fragment-length polymorphism method. The genotype distribution was as follows: CC—142 (58%), CT—85 (35%), and TT—16 (7%). Carriers of the -148T allele had higher preoperative plasma fibrinogen (4.42 ± 0.14 vs. 4.07 ± 0.11 mg/L, p = 0.04) and CRP levels (7.49 ± 1.2 vs. 4.26 ± 1.0 mg/L, p = 0.04) compared with non-carriers; 5 to 7 days after CABG, patients carrying -148T allele had increased CRP (70.4 ± 5.0 vs. 51.6 ± 4.25 mg/L, p = 0.005) and IL-6 levels (22.34 ± 2.64 vs. 15.53 ± 2.28 pg/L, p = 0.05), but not fibrinogen, compared with the remaining subjects. In-hospital nonfatal stroke occurred more frequently in -148T allele carriers (4% vs. 0%, p = 0.02). No genotype-associated differences were found in the occurrence of postoperative myocardial infarction and death. Presence of the -148T allele has also been associated with longer intensive care stay and intubation time (p = 0.01). Multivariate analysis identified the CT+TT genotype as an independent predictor of pre- and postoperative CRP levels. The results indicate that the presence of the -148T FGB allele determines higher pre- and postoperative levels of inflammatory markers, which might be associated with in-hospital clinical outcomes.     

Kinetics of VO2 limb blood flow and regional muscle deoxygenation in young adults during moderate intensity, knee-extension exercise

The kinetics of pulmonary O₂ uptake ( [(V)\dot]\textO _2 \textp ), \left( {\dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} } \right), limb blood flow (LBF) and deoxygenation (ΔHHb) of the vastus lateralis (VL) and vastus medialis (VM) muscles during the transition to moderate-intensity knee-extension exercise (MOD) was examined. Seven males (27 ± 5 years; mean ± SD) performed repeated step transitions (n = 4) from passive exercise to MOD. Breath by breath [(V)\dot]\textO _2 \textp , \dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} , femoral artery LBF, and VL and VM muscle ∆HHb were measured, respectively, by mass spectrometer and volume turbine, Doppler ultrasound and near-infrared spectroscopy. Phase 2 [(V)\dot]\textO _2 \textp , \dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} , LBF, and ∆HHb data were fit with a mono-exponential model. The time constant (τ) of the [(V)\dot]\textO _2 \textp \dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} and LBF response were not different ( t[(V)\dot]\textO _2 \textp , \tau \dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} , 24 ± 6 s; τLBF, 23 ± 8 s). The ∆HHb response did not differ between VL and VM in amplitude (VL 6.97 ± 4.22 a.u.; VM 7.24 ± 3.99 a.u.), time delay (∆HHb_TD: VL 17 ± 2 s; VM 15 ± 1 s), time constant (τ∆HHb: VL 11 ± 6 s; VM 13 ± 4 s), or effective time constant [τ′∆HHb (= ∆HHb_TD + τ∆HHb): VL 28 ± 7 s; VM 28 ± 4 s]. Adjustments in ∆HHb in VL and VM depict a similar balance of regional O₂ delivery and utilization within the quadriceps muscle group. The τ′∆HHb and t[(V)\dot]\textO _2 \textp \tau \dot{V}{{{\text{O}}_{{ 2\,{\text{p}}}} }} were similar, however, the ∆HHb displayed an “overshoot” relative to the steady-state levels reflecting a slower alteration of microvascular blood flow (O₂ delivery) relative to O₂ utilization, necessitating a greater reliance on O₂ extraction.     

A comparison of modelling procedures used to estimate the power–exhaustion time relationship

This study aimed to test the consistency of using the power required to elicit maximal oxygen uptake during incremental test (P _t) to demarcate the range of power intensity in the modelling of the power–exhaustion time relationship. Different mathematical procedures were tested using data from ten subjects exercising on a cycle ergometer. After the determination of P _t and the power at the ventilatory threshold, the subjects did six tests at constant power to exhaustion within 2–15 min. Estimates were obtained from a segmented model using two distinct equations of the anaerobic contribution to power below and above P _t, respectively. This model fit the overall data with a better adequacy than the simple hyperbolic model (standard error of 29.2 ± 25.2 vs. 42.3 ± 25.2 s). The power asymptotes were 225.7 ± 27.3 W from the segmented model, 226.2 ± 27.3 and 283.3 ± 20.5 W from the simple model applied to data below and above P _t, respectively. The estimates from the segmented model were strongly correlated with their analogues from the simple model applied only to data below P _t (R = 1.00 for power asymptote and curvature coefficient). They were not correlated with their analogues from the simple model applied only to data above P _t. These discrepancies between modelling procedures could arise from the method used to determine P _t and the oversimplification of the oxygen uptake kinetics. These limitations could lead the segmented model to an overestimation of the anaerobic contribution which was around 15% of total energy expended at P _t.     

Caffeine improves supramaximal cycling but not the rate of anaerobic energy release

The purpose of this study was to determine if improved supramaximal exercise performance in trained cyclists following caffeine ingestion was associated with enhanced O₂ uptake ( [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics), increased anaerobic energy provision (accumulated O₂—AO₂—deficit), or a reduction in the accumulation of metabolites (for example, K⁺) associated with muscular fatigue. Six highly trained male cyclists ( [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} peak 68 ± 8 mL kg⁻¹ min⁻¹) performed supramaximal (120% [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} peak) exercise bouts to exhaustion on an electronically braked cycle ergometer, following double-blind and randomized ingestion of caffeine/placebo (5 mg kg⁻¹). Time to exhaustion (TE), [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics, AO₂ deficit, blood lactate (La⁻), plasma potassium (K⁺), caffeine and paraxanthine concentrations were measured. Caffeine ingestion elicited significant increases in TE (14.8%, p < 0.01) and AO₂ deficit (6.5%, p < 0.05). In contrast, no changes were observed in AO₂ deficit at isotime, [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics, blood [La⁻] at exhaustion or peak [K⁺] following caffeine ingestion. However, [K⁺] was significantly reduced (13.4%, p < 0.01) during warm-up cycling immediately prior to the onset of the supramaximal bout for the caffeine trials, compared with placebo. It appears that caffeine ingestion is beneficial to supramaximal cycling performance in highly trained men. The reduced plasma [K⁺] during submaximal warm-up cycling may prolong the time taken to reach critical [K⁺] at exhaustion, thus delaying fatigue. Considering caffeine ingestion did not change [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics or isotime AO₂ deficit, increases in absolute AO₂ deficit may be a consequence of prolonged TE, rather than causal.     

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

The β₂-adrenergic receptor (β₂AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the β ₂ AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for β ₂ AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 β₂AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.