Blood shifts between body compartments during submaximal exercise with induced expiratory flow limitation in healthy humans.

External expiratory flow limitation (EFLe) can be applied in healthy subjects to mimic the effects of chronic obstructive pulmonary disease during exercise. At maximal exercise intensity, EFLe leads to exercise intolerance owing to respiratory pump dysfunction limiting venous return. We quantified blood shifts between body compartments to determine whether such effects can be observed during submaximal exercise, when the load on the respiratory system is milder. Ten healthy men (25.2 ± 3.2 years of age, 177.3 ± 5.4 cm in height and weighing 67.4 ± 5.8 kg) exercised at 100 W (∼40% of maximal oxygen uptake) while breathing spontaneously (CTRL) or with EFLe. We measured respiratory dynamics with optoelectronic plethysmography, oesophageal (Pes ) and gastric (Pga ) pressures with balloon catheters, and blood shifting between body compartments with double body plethysmography. During exercise, EFLe resulted in the following changes: (i) greater intrabreath blood shifts between the trunk and the extremities [518 ± 221 (EFLe) vs. 224 ± 60 ml (CTRL); P < 0.001] associated with lower Pes during inspiration (r = 0.53, P < 0.001) and higher Pga during expiration (r = 0.29, P < 0.024); and (ii) a progressive pooling of blood in the trunk over time (∼700 ml after 3 min of exercise; P < 0.05), explained by a predominant effect of lower inspiratory Pes (r = 0.54, P < 0.001) over that of increased Pga . It follows that during submaximal exercise, EFLe amplifies the respiratory pump mechanism, with a prevailing contribution from lower inspiratory Pes over increased expiratory Pga , drawing blood into the trunk. Whether these results can be replicated in chronic obstructive pulmonary disease patients remains to be determined. KEY POINTS: External expiratory flow limitation (EFLe) can be applied in healthy subjects to mimic the effects of chronic obstructive pulmonary disease and safely study the mechanisms of exercise intolerance associated with the disease. At maximal exercise intensity with EFLe, exercise intolerance results from high expiratory pressures altering the respiratory pump mechanism and limiting venous return. We used double body plethysmography to quantify blood shifting between the trunk and the extremities and to examine whether the same effects occur with EFLe at submaximal exercise intensity, where the increase in expiratory pressures is milder. Our data show that during submaximal exercise, EFLe amplifies the respiratory pump mechanism, each breath producing greater blood displacements between the trunk and the extremities, with a prevailing effect from lower inspiratory intrathoracic pressure progressively drawing blood into the trunk. These results help us to understand the haemodynamic effects of respiratory pressures during submaximal exercise with expiratory flow restriction.

Priming the cardiodynamic phase of pulmonary oxygen uptake through voluntary modulations of the respiratory pump at the onset of exercise.

NEW FINDINGS: What is the central question of this study? The initial increase in oxygen uptake ( V̇O2 ) at exercise onset results from pulmonary perfusion changes secondary to an increased venous return. Breathing mechanics contribute to venous return through abdominal and intrathoracic pressures variation. Can voluntary breathing techniques (abdominal or rib cage breathing) increase venous return and improve V̇O2 at exercise onset? What is the main finding and its importance? Abdominal and rib cage breathing increase venous return and V̇O2 at exercise onset. This mechanism could be clinically relevant in patients with impaired cardiac function limiting oxygen transport. ABSTRACT: We examined how different breathing patterns can modulate venous return and alveolar gas transfer during exercise transients in humans. Ten healthy men transitioned from rest to moderate cycling while breathing spontaneously (SP) or with voluntary increases in abdominal (AB) or intrathoracic (RC) pressure swings. We used double body plethysmography to determine blood displacements between the trunk and the extremities (Vbs ). From continuous signals of airflow and O2 fraction, we calculated breath-by-breath oxygen uptake at the mouth and used optoelectronic plethysmography to correct for lung O2 store changes and calculate alveolar O2 transfer ( V̇O2A ). Oesophageal (Poes ) and gastric (Pga ) pressures were monitored using balloon-tipped catheters. Cardiac stroke volume was measured using impedance cardiography. During the cardiodynamic phase (Φ1) of V̇O2A -on kinetics (20 s following exercise onset), AB and RC increased total alveolar oxygen transfer compared to SP (227 ± 32, P = 0.019 vs. 235 ± 27, P = 0.001 vs. 206 ± 20 ml, mean ± SD). Pga and Poes swings increased with AB (by 24.4 ± 9.6 cmH2 O, P < 0.001) and RC (by 14.5 ± 5.7 cmH2 O, P < 0.001), respectively. AB yielded a greater increase in intra-breath Vbs swings compared with RC and SP (+0.30 ± 0.14 vs. +0.16 ± 0.11, P < 0.001 vs. +0.10 ± 0.05 ml, P = 0.006) and increased the sum of stroke volumes compared to SP (4.47 ± 1.28 vs. 3.89 ± 0.96 litres, P = 0.053), while RC produced significant central blood translocation from the extremities compared with SP (by 493 ± 311 ml, P < 0.001). Our findings indicate that combining exercise onset with AB or RC increases venous return, thus increasing mass oxygen transport above metabolic consumption during Φ1 and limiting the oxygen deficit incurred.

Automating the correction of flow integration drift during whole-body plethysmography.

Prolonged measurement of total body volume variations (deltaVb) with whole-body, flow-based plethysmography (WBP) results in a drift of the signal due to changes in temperature and humidity inside the plethysmograph and to numerical integration of the flow to obtain deltaVb. This drift has been previously corrected with the application of a wavelet- based filter using visual inspection of the signal to select the optimal filter level (Uva et al. Front. Physiol. 6:411, 2016), thus introducing potential operator bias. To exclude the latter we compared this approach with a newly developed automatic method based on (1) correction for actual changes in temperature and humidity inside the plethysmograph (algorithm TH) and (2) automatic selection of the wavelet filter level based on comparison between deltaVb and intra-thoracic and abdominal pressure variations measured simultaneously (algorithm WAV). The Pearson's correlation coefficient between deltaVb and the changes in volume of the chest wall (deltaVcw) simultaneously obtained by optoelectronic plethysmography (OEP) was calculated after correction of deltaVb with TH and WAV applied separately, TH and WAV applied consecutively (TH+WAV), manual selection of a wavelet filter based on visual inspection (MAN) or no correction (CTRL). The correlation between deltaVb and deltaVcw increased marginally with WAV, TH+WAV and MAN compared to CTRL (P <; 0.01). Conversely, TH alone yielded a lower correlation (P <; 0.01). It follows that while the automated wavelet filter level selection method (WAV) represents an effective, operator-independent method for the correction of deltaVb, whether or not it is combined with specific correction for changes in thermodynamic conditions inside the plethysmograph, the manual method (MAN) yields satisfactory results without the constraints of intra-thoracic and abdominal pressure measurement.

Mass-normalized internal mechanical work in walking is not impaired in adults with class III obesity.

This study aimed to investigate the effects of obesity on the internal mechanical work, and its influence on the total mechanical work, energy cost, and mechanical efficiency in obese and nonobese adults while walking at different speeds. Body composition and anthropometrical characteristics were obtained for eleven obese [O; 39.9 ± 7.9 yr; body mass index (BMI): 43.0 ± 4.2 kg/m2] and thirteen lean adults (L; 29.6 ± 5.7 yr; BMI: 22.0 ± 1.5 kg/m2). Participants walked at five speeds (0.56, 0.83, 1.11, 1.39, 1.67 m/s) while oxygen consumption was measured to obtain net energy cost of walking (NCw). A motion analysis system and instrumented treadmill were combined to obtain external (Wext), internal (Wint), and total (Wtot) mechanical work, and pendular energy recovery. Mechanical efficiency was calculated as the ratio of Wtot to NCw. Relative NCw (per unit body mass) was significantly higher in O than L (P ≤ 0.001). Relative Wext was significantly lower in O compared with L (P = 0.002), whereas no significant difference was found in relative Wint (P = 0.16) and Wtot (P = 0.6). Recovery was significantly higher (P ≤ 0.001), while mechanical efficiency was significantly lower in O than in L (P ≤ 0.001). These results suggest that individuals with obesity class III have similar mass-normalized Wint and Wtot compared with their lean counterparts, along with a higher relative NCw. Consequently, the efficiency of walking was reduced in this population. These results suggest that mass-normalized Wint is unaffected by obesity and is not responsible for the higher relative NCw and lower efficiency of walking in these individuals.NEW & NOTEWORTHY It has been suggested that internal mechanical work (i.e., the work required to move the limbs with respect to the center of mass, Wint) may be responsible for the higher net cost of walking in obese adults, but this variable has not yet been studied in individuals with obesity. The main finding of the present study is that individuals with class III obesity exhibit a similar amount of mass-normalized Wint to that of adults with a normal body weight, suggesting that body mass-relative Wint is not affected by obesity and is not responsible for the higher energy cost and the lower efficiency of walking in this population.

The Effect of Lower-Body Positive Pressure on the Cardiorespiratory Response at Rest and during Submaximal Running Exercise.

Anti-gravity treadmills facilitate locomotion by lower-body positive pressure (LBPP). Effects on cardiorespiratory regulation are unknown. Healthy men (30 ± 8 y, 178.3 ± 5.7 cm, 70.3 ± 8.0 kg; mean ± SD) stood upright (n = 10) or ran (n = 9) at 9, 11, 13, and 15 km.h-1 (5 min stages) with LBPP (0, 15, 40 mmHg). Cardiac output (CO), stroke volume (SV), heart rate (HR), blood pressure (BP), peripheral resistance (PR), and oxygen uptake (VO2) were monitored continuously. During standing, LBPP increased SV [by +29 ± 13 (+41%) and +42 ± 15 (+60%) ml, at 15 and 40 mmHg, respectively (p < 0.05)] and decreased HR [by -15 ± 6 (-20%) and -22 ± 9 (-29%) bpm (p < 0.05)] resulting in a transitory increase in CO [by +1.6 ± 1.0 (+32%) and +2.0 ± 1.0 (+39%) l.min-1 (p < 0.05)] within the first seconds of LBPP. This was accompanied by a transitory decrease in end-tidal PO2 [by -5 ± 3 (-5%) and -10 ± 4 (-10%) mmHg (p < 0.05)] and increase in VO2 [by +66 ± 53 (+26%) and +116 ± 64 (+46%) ml.min-1 (p < 0.05)], suggesting increased venous return and pulmonary blood flow. The application of LBPP increased baroreflex sensitivity (BRS) [by +1.8 ± 1.6 (+18%) and +4.6 ± 3.7 (+47%) at 15 and 40 mmHg LBPP, respectively P < 0.05]. After reaching steady-state exercise CO vs. VO2 relationships remained linear with similar slope and intercept for each participant (mean R2 = 0.84 ± 0.13) while MAP remained unchanged. It follows that (1) LBPP affects cardiorespiratory integration at the onset of exercise; (2) at a given LBPP, once reaching steady-state exercise, the cardiorespiratory load is reduced proportionally to the lower metabolic demand resulting from the body weight support; (3) the balance between cardiovascular response, oxygen delivery to the exercising muscles and blood pressure regulation is maintained at exercise steady-state; and (4) changes in baroreflex sensitivity may be involved in the regulation of cardiovascular parameters during LBPP.

Meningitis de etiología mixta: tuberculosa y bacteriana por germen no identificado / Meningitis of mixed ethiology (tuberculous and unindentified bacteria)

Se presenta un caso de paciente masculino de 54 años de edad, sin inmunosupresión ni evidencia de la misma durante su hospitalización, que consulta por cefalea y signos meníngeos. Se realiza Punción Lumbar (PL) compatible con meningitis bacteriana por lo que se indica tratamiento empírico con mejoría franca de la sintomatología con excepción de la esorientación. Una vez en mejores condiciones se reciben los valores de la ADA los cuales están elevados compatibles con Tuberculosis Meníngea (TBM). Se realiza nueva PL para confirmar dicho valor, lo que se logra y además se demuestra un aumento leve. A los 20 días de la hospitalización, y luego de la mejoría franca, el paciente presenta nuevamente cefalea, fiebre y bradilalia por lo que se inicia tratamiento anti TB con mejoría progresiva de los síntomas. Se presenta el caso y se revisa la literatura(AU)

We present a 54-year-old male patient, with no immunosuppression who consulted for headache and meningeal signs. Lumbar tap (LT) was compatible with bacterial meningitis and empirical treatment was startes with a clear improvement in symptomatology, except for disorientation. Then ADA values were received and its values were francly compatible with Meningeal Tuberculosis (TBM). A new LT was performed to confirm this value, also showeds a slight increase. Twenty days after the hospitalization, and after the frank improvement, the patient again presented again with headache, fever and bradylalia, thus initiating anti-TB treatment with progressive improvement of symptoms. The case is presented and the literature is reviewed(AU)

Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial.

BACKGROUND: Hypoxia-induced pulmonary vasoconstriction increases pulmonary arterial pressure (PAP) and may impede right heart function and exercise performance. This study examined the effects of oral nitrate supplementation on right heart function and performance during exercise in normoxia and hypoxia. We tested the hypothesis that nitrate supplementation would attenuate the increase in PAP at rest and during exercise in hypoxia, thereby improving exercise performance. METHODS: Twelve trained male cyclists [age: 31 ± 7 year (mean ± SD)] performed 15 km time-trial cycling (TT) and steady-state submaximal cycling (50, 100, and 150 W) in normoxia and hypoxia (11% inspired O2) following 3-day oral supplementation with either placebo or sodium nitrate (0.1 mmol/kg/day). We measured TT time-to-completion, muscle tissue oxygenation during TT and systolic right ventricle to right atrium pressure gradient (RV-RA gradient: index of PAP) during steady state cycling. RESULTS: During steady state exercise, hypoxia elevated RV-RA gradient (p > 0.05), while oral nitrate supplementation did not alter RV-RA gradient (p > 0.05). During 15 km TT, hypoxia lowered muscle tissue oxygenation (p < 0.05). Nitrate supplementation further decreased muscle tissue oxygenation during 15 km TT in hypoxia (p < 0.05). Hypoxia impaired time-to-completion during TT (p < 0.05), while no improvements were observed with nitrate supplementation in normoxia or hypoxia (p > 0.05). CONCLUSION: Our findings indicate that oral nitrate supplementation does not attenuate acute hypoxic pulmonary vasoconstriction nor improve performance during time trial cycling in normoxia and hypoxia.

The "Abdominal Circulatory Pump": An Auxiliary Heart during Exercise?

Apart from its role as a flow generator for ventilation the diaphragm has a circulatory role. The cyclical abdominal pressure variations from its contractions cause swings in venous return from the splanchnic venous circulation. During exercise the action of the abdominal muscles may enhance this circulatory function of the diaphragm. Eleven healthy subjects (25 ± 7 year, 70 ± 11 kg, 1.78 ± 0.1 m, 3 F) performed plantar flexion exercise at ~4 METs. Changes in body volume (ΔVb) and trunk volume (ΔVtr) were measured simultaneously by double body plethysmography. Volume of blood shifts between trunk and extremities (Vbs) was determined non-invasively as ΔVtr-ΔVb. Three types of breathing were studied: spontaneous (SE), rib cage (RCE, voluntary emphasized inspiratory rib cage breathing), and abdominal (ABE, voluntary active abdominal expiration breathing). During SE and RCE blood was displaced from the extremities into the trunk (on average 0.16 ± 0.33 L and 0.48 ± 0.55 L, p < 0.05 SE vs. RCE), while during ABE it was displaced from the trunk to the extremities (0.22 ± 0.20 L p < 0.001, p < 0.05 RCE and SE vs. ABE respectively). At baseline, Vbs swings (maximum to minimum amplitude) were bimodal and averaged 0.13 ± 0.08 L. During exercise, Vbs swings consistently increased (0.42 ± 0.34 L, 0.40 ± 0.26 L, 0.46 ± 0.21 L, for SE, RCE and ABE respectively, all p < 0.01 vs. baseline). It follows that during leg exercise significant bi-directional blood shifting occurs between the trunk and the extremities. The dynamics and partitioning of these blood shifts strongly depend on the relative predominance of the action of the diaphragm, the rib cage and the abdominal muscles. Depending on the partitioning between respiratory muscles for the act of breathing, the distribution of blood between trunk and extremities can vary by up to 1 L. We conclude that during exercise the abdominal muscles and the diaphragm might play a role of an "auxiliary heart."

Concomitant ventilatory and circulatory functions of the diaphragm and abdominal muscles.

Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and abdominal muscles shift substantial quantities of blood from the splanchnic circulation to the extremities. This suggests that the diaphragm assisted by abdominal muscles might accomplish ventilation and circulation simultaneously by repeated EMs. We tested this hypothesis in normal subjects by measuring changes (Δ) in body volume (Vb) by whole body plethysmography simultaneously with changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures the same parameters as whole body plethysmography plus the volume of blood shifts (Vbs) between trunk and extremities: Vbs = ΔVtr-ΔVb. We also measured abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac output (Qc). EMs with abdominal pressure ~100 cmH(2)O for 1 s, followed by 2-s relaxations, repeated over 90 s, produced a "stroke volume" from the splanchnic bed of 0.35 ± 0.07 (SD) liter, an output of 6.84 ± 0.75 l/min compared with a resting Qc of 5.59 ± 1.14 l/min. Refilling during relaxation was complete, and the splanchnic bed did not progressively empty. Diastolic pressure increased by 25 mmHg during each EM. Between EMs, Qc increased to 7.09 ± 1.14 l/min due to increased stroke volume and heart rate. The circulatory function of the diaphragm assisted by simultaneous contractions of abdominal muscles with appropriate pressure and duration at 20 min(-1) can produce a circulatory output as great as resting Qc, as well as ventilation. These combined functions of the diaphragm have potential for cardiopulmonary resuscitation. The abdominal circulatory pump can act as an auxiliary heart.