Plasma volume expansion does not increase maximal cardiac output or VO2 max in lowlanders acclimatized to altitude

[EN] With altitude acclimatization, blood hemoglobin concentration increases while plasma volume (PV) and maximal cardiac output (Qmax) decrease. This investigation aimed to determine whether reduction of Qmax at altitude is due to low circulating blood volume (BV). Eight Danish lowlanders (3 females, 5 males: age 24.0 +/- 0.6 yr; mean +/- SE) performed submaximal and maximal exercise on a cycle ergometer after 9 wk at 5,260 m altitude (Mt. Chacaltaya, Bolivia). This was done first with BV resulting from acclimatization (BV = 5.40 +/- 0.39 liters) and again 2-4 days later, 1 h after PV expansion with 1 liter of 6% dextran 70 (BV = 6.32 +/- 0.34 liters). PV expansion had no effect on Qmax, maximal O2 consumption (VO2), and exercise capacity. Despite maximal systemic O2 transport being reduced 19% due to hemodilution after PV expansion, whole body VO2 was maintained by greater systemic O2 extraction (P < 0.05). Leg blood flow was elevated (P < 0.05) in hypervolemic conditions, which compensated for hemodilution resulting in similar leg O2 delivery and leg VO2 during exercise regardless of PV. Pulmonary ventilation, gas exchange, and acid-base balance were essentially unaffected by PV expansion. Sea level Qmax and exercise capacity were restored with hyperoxia at altitude independently of BV. Low BV is not a primary cause for reduction of Qmax at altitude when acclimatized. Furthermore, hemodilution caused by PV expansion at altitude is compensated for by increased systemic O2 extraction with similar peak muscular O2 delivery, such that maximal exercise capacity is unaffected.

Effect of blood haemoglobin concentration on V(O2,max) and cardiovascular function in lowlanders acclimatised to 5260 m

[EN] The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O(2) consumption (V(O(2),max)) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 +/- 0.6 years, mean +/- S.E.M.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O(2) in N(2)) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V(O(2),max), showing that breathing ambient air at 5260 m, V(O(2),max) is limited by the availability of O(2) rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 +/- 5 to 185 +/- 5 g l(-1) (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 +/- 6 g l(-1) (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V(O(2),max), or power output. Despite higher LBF, leg O(2) delivery was reduced and maximal V(O(2)) was thus maintained by higher O(2) extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (F(I,O(2))), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K(+) concentrations, independently of [Hb] and F(I,O(2)). In summary, under conditions where O(2) supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V(O(2),max), and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V(O(2),max) may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?

[EN] Acute hypoxia (AH) reduces maximal O2 consumption (VO2 max), but after acclimatization, and despite increases in both hemoglobin concentration and arterial O2 saturation that can normalize arterial O2 concentration ([O2]), VO2 max remains low. To determine why, seven lowlanders were studied at VO2 max (cycle ergometry) at sea level (SL), after 9-10 wk at 5,260 m [chronic hypoxia (CH)], and 6 mo later at SL in AH (FiO2 = 0.105) equivalent to 5,260 m. Pulmonary and leg indexes of O2 transport were measured in each condition. Both cardiac output and leg blood flow were reduced by approximately 15% in both AH and CH (P < 0.05). At maximal exercise, arterial [O2] in AH was 31% lower than at SL (P < 0.05), whereas in CH it was the same as at SL due to both polycythemia and hyperventilation. O2 extraction by the legs, however, remained at SL values in both AH and CH. Although at both SL and in AH, 76% of the cardiac output perfused the legs, in CH the legs received only 67%. Pulmonary VO2 max (4.1 +/- 0.3 l/min at SL) fell to 2.2 +/- 0.1 l/min in AH (P < 0.05) and was only 2.4 +/- 0.2 l/min in CH (P < 0.05). These data suggest that the failure to recover VO2 max after acclimatization despite normalization of arterial [O2] is explained by two circulatory effects of altitude: 1) failure of cardiac output to normalize and 2) preferential redistribution of cardiac output to nonexercising tissues. Oxygen transport from blood to muscle mitochondria, on the other hand, appears unaffected by CH.

Timing per l'inserimento in lista dei pazienti affetti da fibrosi cistica che necessitano di trapianto polmonare: casistica di un centro regionale di riferimento

Timing of waiting list entrance for patients with cystic fibrosis in need of pulmonary transplant: the experience of a regional referral centre Objective: Evaluation of parameters that can predict a rapid decay of general conditions of patients affected by Cystic Fibrosis (CF) with no specific criteria to be candidate to pulmonary transplant. Material and methods: Fifteen patients with CF who died for complications and 8 who underwent lung transplantation in the 2000-2010 decade, were enrolled. Clinical data 2 years before the event (body max index, FEV1%, number of EV antibiotic treatments per year, colonization with Methicillin-resistant Staphylococcus aureus (MRSA), pseudomonas aeruginosa mucosus, burkholderia cepacia, pulmonary allergic aspergilosis) were compared among the 2 groups. Results: Mean FEV1% was significantly higher and mean number of antibiotic treatment was lower in deceased than in the transplanted patients (p<0.002 and p<0.001 respectively). Although in patients who died there were no including criteria to enter the transplant list 2 years before the exitus, suggestive findings such as low BMI (17.3), high incidence of hepatic pathology (33.3%), diabetes (50%), and infections with MRSA infection (25%), Pseudomonas aeruginosa (83.3%) and burkholderia cepacia (8.3%) were found with no statistical difference with transplanted patients, suggesting those patients were at risk of severe prognosis. In patients who died, females were double than males. Conclusion: While evaluating patients with CF, negative prognostic factors such as the ones investigated in this study, should be considered to select individuals with high mortality risk who need stricter therapeutical approach and follow up. Inclusion of those patients in the transplant waiting list should be taken into account.

Sguardo sulla società tedesca contemporanea attraverso la proposta di traduzione di alcuni capitoli di Im Sparadies der Friseure: Eine kleine Sprachkritik di Wiglaf Droste e di Ein Buch namens Zimbo: Sie werden kaum ertragen was Ihnen mitgeteilt wird di Max Goldt.

Con il mio elaborato voglio descrivere brevemente la società tedesca e l'evoluzione della sua lingua attraverso la traduzione di alcuni graffianti testi degli scrittori Wiglaf Droste e Max Goldt.

Transport model of the human Na+-coupled L-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-ascorbic acid transport was saturable (K(0.5) approximately 70 microM), temperature dependent (Q(10) approximately 5), and energized by the Na(+) electrochemical potential gradient. We obtained a Na(+)-L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-ascorbic acid and Na(+) saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na(+), L-ascorbic acid, Na(+). In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na(+), maximal charge translocation (Q(max)) was approximately 25 nC, around a midpoint (V(0.5)) at -9 mV, and with apparent valence approximately -1. Q(max) was conserved upon progressive removal of Na(+), whereas V(0.5) shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na(+) partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease.

Le peuple judéo-espagnol : première base mondiale de L'Espagne

par Angel Pulido. Trad. de L'Espagnol, rev. par Max Nordau

Neginot Yiśraẻl (Neginot Israel) : Synagogen-Gesänge für Solo, Soli und Chor ; mit und ohne Orgelbegleitung

componirt von Max Goldstein

Bekanntmachung, die Wahl der Landtags-Abgeordneten betr.: Maximilian II., von Gottes Gnaden König von Bayern, Pfalzgraf bei Rhein, Herzog von Bayern, Franken und in Schwaben etc. etc.: Wir haben mit Rücksicht auf Unsere Erklärung vom Juni l. J. beschlossen und verordnen ...

Welsch (Projektbearbeiter): Festsetzung der Wahlen zum bayerischen Landtag auf den 17. (Urwahlen) und den 24. Juli 1849. Nebst Ãœbersicht der Wahlorte und Wahlbezirke im Regierungsbezirk Pfalz

Charles L. Hallgarten

Ludwig Max Goldberger

L. Levy-Bruhl, Die Seele der Primitiven [Rezension]

Max Prager

Weinberg Max, Ewige Weisheit [Rezension]

L. Baerwald