Near‐infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing

To elevate effects of carbon dioxide (CO₂) retention by way of an increased respiratory load during submaximal exercise (150 W), the concentration changes of oxy‐ (ΔHbO₂) and deoxy‐haemoglobin (ΔHb) of active muscles and the brain were determined by near‐infrared spectroscopy (NIRS) in eight healthy males. During exercise, pulmonary ventilation increased to 33 (28–40) L min^–1 (median with range) with no effect of a moderate breathing resistance (reduction of the pneumotach diameter from 30 to 14 and 10 mm). The end‐tidal CO₂ pressure (P_ETCO ₂) increased from 45 (42–48) to 48 (46–58) mmHg with a reduction of only 1% in the arterial haemoglobin O₂ saturation (S_aO ₂). During control exercise (normal breathing resistance), muscle and brain ΔHbO₂ were not different from the resting levels, and only the leg muscle ΔHb increased (4 (–2–10) μM , P < 0.05). Moderate resistive breathing increased ΔHbO₂ of the intercostal and vastus lateralis muscles to 6 ± (–5–14) and 1 (–7–9) μM (P < 0.05), respectively, while muscle ΔHb was not affected. Cerebral ΔHbO₂ and ΔHb became elevated to 6 (1–15) and 1 (–1–6) μM by resistive breathing (P < 0.05). Resistive breathing caused an increased concentration of oxygenated haemoglobin in active muscles and in the brain. The results indicate that CO₂ influences blood flow to active skeletal muscle although its effect appears to be smaller than for the brain.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.     

Middle cerebral artery blood velocity,arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia

During exercise the transcranial Doppler determined mean blood velocity (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 ± 20 to 92 ± 21 beats min^?1 and mean arterial pressure (MAP) from 87 ± 7 to 105 ± 9 mmHg (mean ± SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 ± 9 mmHg). During handgrip contralateral MCA V_mean increased from 65 ± 10 to 75 ± 13 cm s^?1 and this was more than on the ipsilateral side (from 63 ± 10 to 68 ± 10 cm s^?1; P < 0.05). On both sides of the brain V_mean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 ± 24 to 116 ± 39 units) but the elevation became statistically significant during PEMI (135 ± 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, V_mean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.     

Blood oxygenation level-dependent (BOLD) total and extravascular signal changes and ΔR2* in human visual cortex at 1.5, 3.0 and 7.0 T

The characterisation of the extravascular (EV) contribution to the blood oxygenation level‐dependent (BOLD) effect is important for understanding the spatial specificity of BOLD contrast and for modelling approaches that aim to extract quantitative metabolic parameters from the BOLD signal. Using bipolar crusher gradients, total (b = 0 s/mm²) and predominantly EV (b = 100 s/mm²) gradient echo BOLD ΔR₂* and signal changes (ΔS/S) in response to visual stimulation (flashing checkerboard; f = 8 Hz) were investigated sequentially (within < 3 h) at 1.5, 3.0 and 7.0 T in the same subgroup of healthy volunteers (n = 7) and at identical spatial resolutions (3.5 × 3.5 × 3.5 mm³). Total ΔR₂* (z‐score analysis) values were ?0.61 ± 0.10 s^?1 (1.5 T), ?0.74 ± 0.05 s^?1 (3.0 T) and ?1.37 ± 0.12 s^?1 (7.0 T), whereas EV ΔR₂* values were ?0.28 ± 0.07 s^?1 (1.5 T), ?0.52 ± 0.07 s^?1 (3.0 T) and ?1.25 ± 0.11 s^?1 (7.0 T). Although EV ΔR₂* increased linearly with field, as expected, it was found that EV ΔS/S increased less than linearly with field in a manner that varied with TE choice. Furthermore, unlike ΔR₂*, total and EV ΔS/S did not converge at 7.0 T. These trends were similar whether a z‐score analysis or occipital lobe‐based region‐of‐interest approach was used for voxel selection. These findings suggest that calibrated BOLD approaches may benefit from an EV ΔR₂* measurement as opposed to a ΔS/S measurement at a single TE. Copyright © 2010 John Wiley & Sons, Ltd.     

Oxygen‐induced frequency shifts in hyperoxia: a significant component of BOLD signal

In comparison to the well‐documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood‐oxygen‐level‐dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r₁ and r₂ (relaxivities) of the oxygen‐treated serum were 0.22 mM^?1 · s^?1and 0.19 mM^?1 · s^?1_, respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18–42% of measured brain regions, voxels with accompanying significant decreases in both the T₂^* (?12.1% to ?19.4%) and T₁ (?5.8% to ?3.3%) relaxation times. In contrast, the T₂^* relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41–50% of the measured brain), which reflected a hyperoxygenation‐induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia‐driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen‐induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, ?9.8% to ?12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia. Copyright © 2014 John Wiley & Sons, Ltd.     

Hydrolysis kinetics of terephthalic and 5-sulfonatoisophthalic acid esters

The saponification reaction of bis(2-hydroxyethyl) terephthalate ( 3 ) and sodium 3,5-bis(2-hydroxyethoxycarbonyl)benzenesulfonate ( 6 ) was followed under pH-stat conditions in the alkaline pH range (pH 8 to 10 at 50 to 80°C) to determine the consecutive reaction rate constants for the hydrolysis of the diesters and the intermediate monoesters. The observed overall reaction rate constants were split into the individual rate constants for the hydrolysis catalyzed by the solvent, the OH^? ions, the SO groups and the COO^? groups (k₀, k_OH?, k_SO, kCOO?, respectively). No intermolecular catalysis by either the sulfonato or the carboxylato groups and no “autocatalysis” by the solvent was found. The activation parameters for the hydrolysis of the corresponding esters of both acids are equal; for the diesters 3 and 6 : ΔH^? = 73,7 (72,0) kJ mol^?1 [17,6 (17,2) kcal mol^?1], ΔG^? = 103,8 (104,7) kJ mol^?1 [24,8 (25,0) kcal mol^?1], ΔS^? = ?89,6 (?97,6) J mol^?1 K^?1 [?21,4 (?23,3) cal mol^?1 K^?1]; for the monoesters [terephthalic acid mono(2-hydroxyethyl) ester and 5-sodiumsulfonatoisophthalic acid mono(2-hydroxyethyl) ester]: ΔH^? = 80,4 (78,7) kJ mol^?1 [19,2 (18,8) kcal mol^?1], ΔG^? = 109,3 (109,7) kJ mol^?1 [26,1 (26,2) kcal mol^?1], ΔS^? = ?86,3 (?93,0) J mol^?1 K^?1 [?20,6 (?22,2) cal mol^?1 K^?1]. It is concluded that disorders in the fine structure of polyester fibers modified with sulfonato group containing comonomers may primarily be responsable for their lower hydrolytic stability and not any catalytic effects of these groups.     

An electrical admittance based index of thoracic intracellular water during head-up tilt in humans

During 50° head-up tilt (HUT), the number of erythrocytes within the thorax has been shown to be reduced by approximately 25% and this level is retained during a maintained tilt, whilst that in the thigh increases by approximately 70%. To evaluate whether the electrical admittance of intracellular water (ICW) may be used to monitor this redistribution of red cells in humans, we determined the regional difference in the reciprocal value of the impedance at 1.5 and 100 kHz for the thorax (thorax_ICW) and for the leg (leg_ICW). In ten subjects all variables remained unchanged during head-down tilt but during HUT, presyncopal symptoms were induced in eight subjects after a mean of 27 (SEM 7) min as mean heart rate dropped from 85 (SEM 4) to 66 (SEM 3) beats · min⁻¹, mean arterial blood pressure from 80 (SEM 3) to 60 (SEM 5) mmHg, and mean oxygen saturation of venous blood from 76 (SEM 2)% to 73 (SEM 3)% (P < 0.05). The mean haematocrit increased from 50 (SEM 5)% to 52.5 (SEM 3.5)% (P < 0.01) and mean central venous pressure decreased during tilting (from a mean of 1 (SEM 1) to a mean of −1 (SEM 1) mmHg; P < 0.05) and returned to value at rest during the maintained tilt. Mean thoracic impedances increased by 7.0 (SEM 1.0) Ω (1.5 kHz) and 5.4 (SEM 1.2) Ω (100 kHz), and mean leg impedances decreased by 9.3 (SEM 1.2) Ω (1.5 kHz) and 3.1 (SEM 1.0) Ω (100 kHz) (P < 0.01). Mean thorax_ICW decreased at 40° HUT and remained reduced by 11 (SEM 2) S · 10⁻⁴ (P < 0.05) until the presyncopal symptoms developed, at which time it was lower by 16 (SEM 2) S · 10⁻⁴ (P < 0.01). Mean leg_ICW increased from 97 (SEM 15) to 99 (SEM 15) S · 10⁻⁴ (P=0.08) during HUT but decreased during maintained tilt (to 94 (SEM 15) S · 10⁻⁴; P < 0.05). The results suggested that during HUT, the difference in electrical admittance at a high and a low frequency current reflects the reduced number of red cells within the thorax. Accepted: 10 July 2000     

Thoracic impedance and pulmonary atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in humans

Head up and down tilts were used for manipulating the central blood volume in eight volunteers. During head-up tilt thoracic electrical impedance (TI) increased from 36.7 (33.9–52.1) ohm (mean and range) to 41.9 (36.9–59.2) ohm, heart rate from 60 (49–72) to 80 (65–90) beats min^-1 (P < 0.05) and decreased again to 57 (48–67) beats min^-1 accompanying a fall in mean arterial pressure from 86 (76–97) to 54 (41–79) mmHg and in cardiac output from 9.2 (5.9–12.1) to 6.9 (3.4–8.8) 1 min-¹ (n= 7, P < 0.07). Central venous pressure did not change significantly. Pulmonary arterial mean, 6 (3–12) mmHg, and wedge pressures, 4 (1–9) mmHg, decreased to 4 (1–11) and 1 (0–7) mmHg, respectively, and mixed, 78 (77–79%), and central venous oxygen saturations, 72 (71–73)%, fell to 62 (46–75) and 54 (44–58)%, respectively (P < 0.05). Atrial natriuretic peptide (ANP) was determined from blood of the superior vena cava and pulmonary and brachial arteries. Pulmonary artery ANP, 18.4 (7.5–30.7) pmol l^-1, was higher than in vena cava, 13.3 (5.2–20.9) pmol 1^_1 (P < 0.05). At the time of presyncope, pulmonary artery ANP decreased from 20.8 (37.4–10.1) to 13.7 (19.7-5.7) pmol l^-1, in vena cava from 13.8 (23.1–7.1) to 10.2 (17.9-6.7) pmol l^-‘ and in the brachial artery from 16.9 (34.1–5.2) to 11.3 (18.5-5.1) pmol l“¹ (P < 0.05). Head-down tilt did not affect the recorded variables significantly. Thoracic electrical impedance, pulmonary artery pressure and venous oxygen saturations were sensitive indices of the central blood volume as reflected in the release of atrial natriuretic peptide from the right side of the heart.     

Influence of upper body position on middle cerebral artery blood velocity during continuous positive airway pressure breathing

Continuous positive airway pressure (CPAP) is a treatment modality for pulmonary oxygenation difficulties. CPAP impairs venous return to the heart and, in turn, affects cerebral blood flow (CBF) and augments cerebral blood volume (CBV). We considered that during CPAP, elevation of the upper body would prevent a rise in CBV, while orthostasis would challenge CBF. To determine the body position least affecting indices of CBF and CBV, the middle cerebral artery mean blood velocity (MCA V _mean) and the near-infrared spectroscopy determined frontal cerebral hemoglobin content (cHbT) were evaluated in 11 healthy subjects during CPAP at different body positions (15° head-down tilt, supine, 15°, 30° and 45° upper body elevation). In the supine position, 10 cmH₂O of CPAP reduced MCA V _mean by 9 ± 3% and increased cHbT by 4 ± 2 μmol/L (mean ± SEM); (P < 0.05). In the head-down position, CPAP increased cHbT to 13 ± 2 μmol/L but left MCA V _mean unchanged. Upper body elevation by 15° attenuated the CPAP associated reduction in MCA V _mean (−7 ± 2%), while cHbT returned to baseline (1 ± 2 μmol/L). With larger elevation of the upper body MCA V _mean decreased progressively to −17 ± 3%, while cHbT remained unchanged from baseline. These results suggest that upper body elevation by ∼15° during 10 cmH₂O CPAP prevents an increase in cerebral blood volume with minimal effect on cerebral blood flow.     

BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans

To understand and predict the blood‐oxygenation level‐dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (ΔCBF) and volume (ΔCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power‐law, derived from primate data, where the power coefficient (α) was found to be 0.38. The validity of this general formulation has been examined previously, and an α of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (ΔCMRo₂) using calibrated BOLD. However, the direct use of this relationship has been the subject of some debate, since it is well established that the BOLD signal is primarily modulated by changes in ‘venous’ CBV (ΔCBV_v, comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet ΔCBV_v measurements in humans have been extremely scarce. In this work, we demonstrate reproducible ΔCBV_v measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady‐state ΔCBV_v and ΔCBF measurements in human subjects undergoing graded visual and sensorimotor stimulation. We found that: (1) a BOLD‐specific flow‐volume power‐law relationship is described by α = 0.23 ± 0.05, significantly lower than Grubb's constant of 0.38 for total CBV; (2) this power‐law constant was not found to vary significantly between the visual and sensorimotor areas; and (3) the use of Grubb's value of 0.38 in gradient‐echo BOLD modeling results in an underestimation of ΔCMRo₂. Copyright © 2009 John Wiley & Sons, Ltd.     

Macroion-pairs and macroions in the kinetics of polymerization of hexamethylene oxide (oxepane)

Cationic polymerization of oxepane (hexamethylene oxide) ( 1 ) in CH₂Cl₂ and C₆H₅NO₂ as solvents was initiated with 1,3-dioxolan-2-ylium hexafluoroantimonate ( 2 ). Dissociation constants (K_D) of the ion-pairs of polyoxepane into ions were measured: K_D (in CH₂Cl₂, T = 25°C) = 2,8·10^?5 mol·l^?1 [ΔH_D = ?3,8 kJ·mol^?1 (?0,9 kcal·mol^?1), ΔS_D = ?98 J·mol^?1·K^?1 (?23,4 cal·mol^?1·K^?1)]; K_D (in C₆H₅NO₂, T = 25°C) = 1,6·10^?3 mol·l^?1 [ΔH_D = ?7,1 kJ·mol^?1 (?1,7 kcal·mol^?1), ΔS_D = ?78 J·mol^?1·K^?1 (?18,7 cal·mol^?1·K^?1)]; these values are close to those of the ion-pairs of polytetrahydrofuran. Rate constants k_p⁺ and k_p^±, determined from the kinetic measurements for degrees of dissociation of macroion-paris ranging from 0,02 to 0,21 (in CH₂Cl₂) and from 0,09 to 0,7 (in C₆H₅NO₂), were found to be identical within an experimental error of kinetic measurements. The activation parameters of propagation were measured and their dependences on the polarity of the polymerization mixtures are discussed.     

Enhanced cerebral CO2 reactivity during strenuous exercise in man

Light and moderate exercise elevates the regional cerebral blood flow by ~20% as determined by ultrasound Doppler sonography (middle cerebral artery mean flow velocity; MCA V _mean). However, strenuous exercise, especially in the heat, appears to reduce MCA V _mean more than can be accounted for by the reduction in the arterial CO₂ tension (P _aCO₂). This study evaluated whether the apparently large reduction in MCA V _mean at the end of exhaustive exercise relates to an enhanced cerebrovascular CO₂ reactivity. The CO₂ reactivity was evaluated in six young healthy male subjects by the administration of CO₂ as well as by voluntary hypo- and hyperventilation at rest and during exercise with and without hyperthermia. At rest, P _aCO₂ was 5.1±0.2 kPa (mean ± SEM) and MCA V _mean 50.7±3.8 cm s⁻¹ and the relationship between MCA V _mean and P _aCO₂ was linear (double-log slope 1.1±0.1). However, the relationship became curvilinear during exercise (slope 1.8±0.1; P<0.01 vs. rest) and during exercise with hyperthermia (slope 2.3±0.3; P<0.05 vs. control exercise). Accordingly, the cerebral CO₂ reactivity increased from 30.5±2.7% kPa⁻¹ at rest to 61.4±10.1% kPa⁻¹ during exercise with hyperthermia (P<0.05). At exhaustion P _aCO₂ decreased 1.1±0.2 kPa during exercise with hyperthermia, which, with the determined cerebral CO₂ reactivity, accounted for the 28±10% decrease in MCA V _mean. The results suggest that during exercise changes in cerebral blood flow are dominated by the arterial carbon dioxide tension.     

Cholinergic induced mesenteric vasorelaxation in response to head-up tilt

Central hypovolaemia induced by head-up tilt evokes a reduction in superior mesenteric artery resistance resulting in maintenance of regional blood flow. Mechanisms of importance for this response are not known, but a parasympathetic contribution could be expected. To evaluate this hypothesis, superior mesenteric artery blood flow and resistance were evaluated by duplex ultrasound in eight healthy volunteers during postprandial head-up tilt with and without cholinergic blockade. During supine rest, cholinergic blockade did not influence the postprandial reduction in peripheral mesenteric artery resistance as expressed by analogous elevations in the diastolic blood velocity (to 62 ± 9 vs. 56 ± 7 cm s^–1 with placebo). Throughout the normotensive and hypotensive phases of head-up tilt, cholinergic blockade reduced mesenteric artery mean blood velocity by 39 and 42%, respectively, corresponding to volume flow reductions by 35 and 41% (0.62 ± 0.10 vs. 0.96 ± 0.13 L min^–1 and 0.52 ± 0.07 vs. 0.88 ± 0.16 L min^–1; P < 0.05). Also, during both phases of head-up tilt, cholinergic blockade increased mesenteric artery resistance as reflected in a reduction in the diastolic blood velocity by 41 and 56%, respectively (44 ± 4 vs. 74 ± 13 cm s^–1 and 24 ± 6 vs. 54 ± 8 cm s^–1). These results support a cholinergic contribution to the mesenteric artery vasorelaxing response to central hypovolaemia induced by head-up tilt.     

The postural reduction in middle cerebral artery blood velocity is not explained by PaCO2

In the normocapnic range, middle cerebral artery mean velocity (MCA V _mean) changes ∼ 3.5% per mmHg carbon-dioxide tension in arterial blood (PaCO₂) and a decrease in PaCO₂ will reduce the cerebral blood flow by vasoconstriction (the CO₂ reactivity of the brain). When standing up MCA V _mean and the end-tidal carbon-dioxide tension (PETCO₂) decrease, suggesting that PaCO₂ contributes to the reduction in MCA V _mean. In a fixed body position, PETCO₂ tracks changes in the PaCO₂ but when assuming the upright position, cardiac output decreases and its distribution over the lung changes, while ventilation increases suggesting that PETCO₂ decreases more than PaCO₂. This study evaluated whether the postural reduction in PaCO₂ accounts for the postural decline in MCA V _mean. From the supine to the upright position, PETCO₂, PaCO₂, MCA V _mean, and the near-infrared spectrophotometry determined cerebral tissue oxygenation (CO₂Hb) were followed in seven subjects. When standing up, MCA V _mean (from 65.3±3.8 to 54.6±3.3 cm s⁻¹ ; mean ± SEM; P<0.05) and cO₂Hb (−7.2±2.2 μmol l⁻¹ ; P<0.05) decreased. At the same time, the ratio increased 49±14% (P<0.05) with the postural reduction in PETCO₂ overestimating the decline in PaCO₂ (−4.8±0.9 mmHg vs. −3.0±1.1 mmHg; P<0.05). When assuming the upright position, the postural decrease in MCA V _mean seems to be explained by the reduction in PETCO₂ but the small decrease in PaCO₂ makes it unlikely that the postural decrease in MCA V _mean can be accounted for by the cerebral CO₂ reactivity alone.     

Biphasic intra-thoracic pressure regulation augments cardiac index during porcine peritonitis: a feasibility study

Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital to maintaining tissue oxygenation in sepsis. This feasibility study tested the hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered with a novel device, was designed to non-invasively enhance venous return by creating sub-atmospheric intra-thoracic pressure during the expiratory phase of mechanical ventilation, improves CO without fluid resuscitation in a porcine E. coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and instrumented with a Swan-Ganz and femoral artery catheter. After a 30?min basal period, a fibrin clot containing 4–5?×?10⁹ cfu kg^?1 E. coli O111.B4 was implanted in the peritoneum. One hour after clot implantation, tIPR was utilized for 30?min and then removed from the ventilator circuit for 30?min. This tIPR cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by comparing pre-tIPR values to peak values during tIPR administration. Following peritonitis, tIPR significantly increased the peak cardiac index (mean?±?SEM) (14.8?±?2.6 vs 7.9?±?2.3?ml kg^?1) and mean arterial pressure (10.2?±?1.5 vs 4.9?±?1.1?mmHg) and simultaneously decreased PAP (?7.7?±?1.5 vs ?2.7?±?0.8?mmHg). These results support the feasibility of the concept that therapeutic application of negative expiratory pressure may provide a non-invasive and complementary approach to increase cardiac output and organ perfusion in the setting of septic shock.     

Heterogeneous oxygenation in nonexercising triceps surae muscle during contralateral isometric exercise

To test whether changes in oxygenation of a resting skeletal muscle, evoked by a static contraction in a contralateral muscle, is uniform within a given skeletal muscle, we used near-infrared spectroscopy (NIRS). Seven subjects performed 2 min static knee extension exercise at 30% of maximal voluntary contraction. Changes in oxygenated hemoglobin (HbO₂) were monitored using multiple-channel NIRS (40 channels, 13 sources and 12 detectors) attached on the contralateral nonexercising triceps surae muscle. Changes in HbO₂ were expressed as a percentage of total labile signals. To characterize the distribution of changes in HbO₂, channels were compared between their positions on the triceps surae muscle, and represented as ‘proximal versus distal’ and ‘lateral versus medial’ portions. During static muscle contraction, the averaged changes in HbO₂ of all channels were correlated with those in calf blood flow (plethysmography; R ²=0.188, P<0.05) and with calf vascular conductance (R ²=0.146, P<0.05). HbO₂ did not differ significantly between the lateral and medial portions of the triceps surae muscle. In contrast, the decrease of HbO₂ in the proximal portion of the muscle was greater than that of the distal portion (P<0.05). These results indicate that the changes in oxygenation of a resting muscle, evoked by static contraction of the contralateral muscle, are heterogeneous.     

Über die polymerisation von 1-chlor-2,3-epoxypropan

The kinetics and the thermodynamic features of the polymerization of 1-chloro-1,3-epoxypropane with the complex \documentclass{article}\pagestyle{empty}\begin{document}${\rm Cl}_{\rm 5} \mathop {{\rm Sb}}\limits^ \ominus \cdots \mathop {\rm S}\limits^ \oplus {\rm O}_2$\end{document} were studied. It was found that the process proceeds with a negative temperature coefficient, E_a=?51,29 kJ/mol ( ? 12,25 kcal/mol), ΔH_p=?18,8 kJ/mol (?4,5kcal/mol), ΔS_p=?74,5 J mol^?1 K^?1 (?17,8 cal mol^?1 K^?1), and with the ceiling temperature of 52,6°C. The molecular masses of the polymers were determined and a possible mechanism of the polymerization process was suggested.     

Middle cerebral artery blood velocity and plasma catecholamines during exercise

During dynamic exercise, mean blood velocity (V_mean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate V_mean at a given volume flow. To evaluate transcranial Doppler-determined V_mean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the V_mean was elevated by 21±3% (mean±SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer, V_mean increased by 31±3% and 48±4%, respectively, and this was significantly higher compared to handgrip (P<0.05). During maximal cycling, plasma adrenaline increased from 0.21±0.04 nmol L^-1 at rest to 4.18±1.46 nmol L^-1, and noradrenaline increased from 0.79±0.08 to 12.70±1.79 nmol L^-1. These levels were 12- to 16-fold higher than those during rhythmic handgrip (adrenaline: 0.34±0.03 nmol L^-1; noradrenaline: 0.78±0.05 nmol L^-1). The increase in V_mean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.     

Influence of Naloxone on the cellular immune response to head-up tilt in humans

To evaluate a possible role for β-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P?=?0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16⁺ and CD56⁺ NK cells in blood. In support, NK cell activity boosted with interferon-α and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105?min. The total lymphocyte count and the concentrations of CD3⁺, CD4⁺, CD8⁺, CD16⁺, and CD56⁺ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30?min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or β-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma β-endorphin was too small to influence the modulation of the cellular immune system.