Konrad E Bloch

University of Zurich, Zürich, Zurich, Switzerland

Are you Konrad E Bloch?

Claim your profile

Publications (176)887.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Arterial and thromboembolic pulmonary hypertension (PH) lead to arterial hypoxaemia. To investigate whether cerebral tissue oxygenation (CTO) in patients with PH is reduced and whether this is associated with reduced exercise tolerance. 16 patients with PH (mean pulmonary arterial pressure ≥25 mmHg, 14 arterial, 2 chronic thromboembolic) and 15 controls underwent right heart catheterisation with monitoring of CTO at rest, during maximal bicycle exercise and during inhalation of oxygen and NO. The 6 min walk distance (6MWD) was measured. Median CTO in PH-patients at rest was 62 % (quartiles 53; 71), during exercise 60 % (53; 65); corresponding values in controls were 65 % (73; 73) (P = NS) and 68 % (66; 70) (p = .013 vs. PH). Inhalation of NO and oxygen improved CTO in PH. In multivariate regression analysis CTO at maximal exercise predicted the work load achieved when controlled for age, pulmonary vascular resistance and mixed venous oxygen saturation (R (2) = .419, p < .000); in addition, the 6MWD was predicted by CTO (adjusted R (2) = .511, p < .000). In PH-patients but not in controls CTO decreased during exercise. Since CTO was an independent predictor of the work load achieved and the 6MWD cerebral hypoxia may contribute to exercise limitation in PH. Clinicaltrials.gov: NCT01463514.
    Beiträge zur Klinik der Tuberkulose 11/2014; 193(1). DOI:10.1007/s00408-014-9667-5 · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several studies showed beneficial effects of sleep on memory performance. Slow waves, the electroencephalographic characteristic of deep sleep, reflected on the neuronal level by synchronous slow oscillations, seem crucial for these benefits. Traveling to moderate altitudes decreases deep sleep. In a randomized cross-over design healthy male subjects performed a visuo-motor learning task in Zurich (490 m) and at Davos Jakobshorn (2590 m) in random order. Memory performance was assessed immediately after learning, before sleep, and in the morning after a night of sleep. Sleep EEG recordings were performed during the nights. Our findings show an altitude induced reduction of sleep dependent memory performance. Moreover, this impaired sleep dependent memory performance was associated with reduced slow wave derived measures of neuronal synchronization. Our results are consistent with a critical role of slow waves for the beneficial effects of sleep on memory that is susceptible to natural environmental influences.
    Physiology & Behavior 11/2014; DOI:10.1016/j.physbeh.2014.11.033 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary hypertension (PH) due to COPD has dismal prognosis. We reviewed the long-term effect of PH-target therapy in severe PH-COPD.
    Beiträge zur Klinik der Tuberkulose 10/2014; DOI:10.1007/s00408-014-9650-1 · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Obstructive sleep apnoea (OSA) is a risk factor for hypertension and associated with increased cardiovascular risk. Continuous positive airway pressure (CPAP) is presumed to be an everyday therapy and has been shown to reduce blood pressure and improve other measures of vascular risk. It is not known whether short-term CPAP withdrawal results in impaired myocardial perfusion and thus, might increase the risk for myocardial ischemia. Objective We assessed the effect of a short-term CPAP withdrawal on myocardial perfusion in patients with OSA. Methods 45 patients with moderate to severe OSA, currently on CPAP, were randomised to either continue or withdraw CPAP (subtherapeutic CPAP) for two weeks. Sleep studies and cardiac positron emission tomography to assess myocardial perfusion were performed at baseline and at two weeks. Results CPAP withdrawal led to a recurrence of OSA (mean difference in AHI between groups +39.7/h, 95%CI 32.7 to 46.7/h, p<0.001). In comparison to continuing CPAP, subtherapeutic CPAP led to a statistically significant increase in morning blood pressure; mean difference in systolic blood pressure +10.8mmHg (95%CI 5.2 to 16.4mmHg) and diastolic blood pressure +7.5mmHg (95%CI 3.5 to 11.5mmHg, both p<0.001), but was not associated with deterioration of myocardial perfusion (mean difference in hyperaemic myocardial blood flow -0.09ml/min/g, 95%CI -0.17 to -0.36ml/min/g, p=0.907). Conclusions Although short-term CPAP therapy withdrawal leads to a considerable increase in blood pressure, it is not associated with impaired myocardial perfusion. Thus, short-term discontinuation of CPAP does not seem to increase the risk of myocardial ischemia.
    Annual Congress of the European Respiratory Society (ERS), Munich, Germany; 09/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Based on meta-analyses, the blood pressure (BP) lowering effect of continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) is reported to be 2mmHg. This figure is derived from trials often limited by poor CPAP compliance, thus, underestimating the effect of CPAP treatment. We analysed BP data from randomised-controlled CPAP withdrawal trials which included only optimally CPAP compliant patients. Methods 145 OSA patients on CPAP were randomised to continue therapeutic (n=62) or to withdraw CPAP (n=83) for two weeks. Morning BP was measured at home before and in hospital after sleep studies. Results CPAP withdrawal was associated with a return of OSA (apnoea-hypopnoea index (AHI) at baseline 2.8/h, at follow-up 33.2/h). Systolic office BP increased in the CPAP withdrawal group compared to CPAP continuation by +6.5mmHg (95%CI 2.6-10.4mmHg, p=0.001) and systolic home BP by +9.7mmHg (95%-CI 6.3-13.0mmHg, p<0.001); diastolic office BP increased by +5.0mmHg (95%CI 2.4-7.6mmHg, p<0.001) and diastolic home BP by +7.9mmHg (95%CI 5.6-10.3mmHg, p<0.001). AHI, baseline systolic BP, statins, gender and number of antihypertensive drugs were independently associated with systolic BP change in multivariate analysis controlled for age, BMI, smoking, diabetes, and sleepiness. Change in diastolic BP was independently predicted by AHI, baseline diastolic BP, and statins. Conclusions Short-term CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials and may be underestimated if only office BP values are used. OSA severity and baseline BP seem to be predictors of BP response to CPAP.
    Annual Congress of the European Respiratory Society (ERS) 2014, Munich, Germany; 09/2014
  • European Respiratory Journal 09/2014; 44(3):578-84. DOI:10.1183/09031936.00109314 · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Sleep-disturbed breathing (SDB) is common in patients with pre-capillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in PH-patients and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization and arrhythmias in patients with PH and SDB. Methods:In a randomized, placebo-controlled, double-blind, cross-over trial 23 patients with arterial (n=16) or chronic thromboembolic PH (n=7) and SDB defined as a mean nocturnal oxygen saturation (SpO2)<90% or dips(>3%)>10/h with daytime PaO2≥7.3kPa were studied. Participants received NOT (3l/min), acetazolamide tablets (2x250mg), and sham-NOT/placebo each during one week separated by a one-week washout period. Three-lead electrocardiography was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and at early morning and nocturnal arrhythmias were counted. Results:NOT was associated with a lower overnight (68±10 vs. 72±9bpm, p=0.010) and early morning heart rate compared with placebo. At late evening, the PQc-time was increased under acetazolamide compared with placebo (mean difference 10ms, 95%CI 0 to 20ms, p=0.042). In the morning under NOT, the QTc-interval was decreased compared with placebo (mean difference -25ms, 95%CI -45 to -6ms, p=0.007) and the TpTec-interval shorter compared with acetazolamide (mean difference -11ms, 95%CI -21 to -1ms, p=0.028). Arrhythmias were rare and similar with all treatments. Conclusions:In PH-patients with SDB, NOT reduces nocturnal heart rate and QTc in the morning thus favorably modifying prognostic markers. Clinical Trial Registration:This trial is registered at clinicalTrials.gov: NTC-01427192.
    Chest 07/2014; DOI:10.1378/chest.14-0495 · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sleep disordered breathing may impair cerebral oxygenation in patients with obstructive sleep apnea syndrome (OSA), in particular during altitude travel. We studied cerebral tissue oxygenation (CTO) in OSA patients at low and moderate altitude, and evaluated whether acetazolamide improved CTO. 18 OSA patients living at <600m discontinued CPAP therapy during studies in Zurich (490m) and during 2 sojourns of 3 days in the Swiss Alps (2 days at 1860m, 1 day at 2590 m) separated by a 2-week washout period at <600m. Patients received acetazolamide (2x250mg/d) or placebo at altitude in a randomized, double-blind, cross-over design. Nocturnal polysomnography including CTO-monitoring by near-infrared spectroscopy(NIRS) was performed. At 490m, medians of CTO, pulse oximetry (SpO2), and apnea/hypopnea index were 65%, 93%, and 57.3/h. At 2590m, on placebo, corresponding values were 59%, 86%, 86.4/h (P<0.05, all corresponding comparisons). Acetazolamide increased CTO and SpO2 at 2590m by mean values (95% CI) of 2% (0-4) and 2% (1-3), and reduced the apnea/hypopnea index by 23.4/h (14.0-32.8) (P<0.05, all changes). Cerebral total hemoglobin concentration, a NIRS-derived surrogate reflecting regional cerebral blood volume, increased by a similar degree in response to apneas at 490m and 2590m, and during acetazolamide and placebo treatment. In OSA patients staying at altitude nocturnal cerebral and arterial oxygenation were reduced in association with exacerbated sleep apnea. Acetazolamide partially improved CTO, SpO2 and sleep apnea without impairing the cerebral blood flow response to apneas. www.clinicaltrials.gov: NCT00714740.
    Chest 05/2014; 146(2). DOI:10.1378/chest.13-2967 · 7.13 Impact Factor
  • Pneumologie 05/2014; 68(05). DOI:10.1055/s-0034-1375918
  • [Show abstract] [Hide abstract]
    ABSTRACT: Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential. © 2014 S. Karger AG, Basel.
    Respiration 04/2014; 87(6). DOI:10.1159/000358439 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy. Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed. Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m. Study 1: 39 OSAS patients. Study 2: 41 OSAS patients. Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500-750 mg) or placebo at moderate altitudes. An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5-10%) and increase in beta activity (approximately 25%). The higher evening dose of 500 mg acetazolamide showed the "spectral fingerprint" of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.
    PLoS ONE 04/2014; 9(4):e93931. DOI:10.1371/journal.pone.0093931 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Kriemler, Susi, Flavia Bürgi, Christian Wick, Birgit Wick, Melanie Keller, Urs Wiget, Christian Schindler, Beat A. Kaufmann, Malcolm Kohler, Konrad Bloch, and Hans-Peter Brunner-La Rocca. Prevalence of acute mountain sickness at 3500 m within and between families: A prospective cohort study. High Alt Biol Med 15:000-000, 2014.-Aim: To investigate symptoms, prevalence and associated factors of acute mountain sickness (AMS) in families upon a fast ascent to 3450 m. Methods: 87 children, 70 adolescents, and 155 parents (n=312) were assessed for AMS 8-10 and 20-24 hours after fast passive ascent by the Lake Louise Score (LLS). Pain sensitivity and oxygen saturation (SO2) were measured and familial clustering was assessed. Results: AMS prevalence was significantly lower in children (21%) compared to adolescents (34%) and adults (39%) on day 1 (p<0.05), but not on day 2 (18% vs. 19% and 25%). Cumulative prevalence of AMS was 30, 37, and 45% in children, adolescents, and adults, respectively (p<0.001). Familial clustering of AMS was consistent and explained 25%-50% of variability in AMS. Pain sensitivity significantly increased from low to high altitude and was higher at low altitude in those with compared to those without AMS. SO2 at high altitude was not related to the presence of AMS. Conclusions: After fast ascent to 3500 m, AMS prevalence was lower in children than in adolescents and adults on day 1, but not on day 2. Thus, children may travel at least as safely to an altitude of 3500 m as adolescents and adults, even if risk factors (pain sensitivity and heredity) are present.
    High altitude medicine & biology 02/2014; 15(1). DOI:10.1089/ham.2013.1073 · 1.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.
    Journal of Sleep Research 02/2014; DOI:10.1111/jsr.12131 · 2.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/μl 95 % CI -370.8/-119.0, lactadherin+ -202/μl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/μl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 μl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.
    Arbeitsphysiologie 02/2014; DOI:10.1007/s00421-014-2837-6 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are limited data on the evolution of obstructive sleep apnoea (OSA) during continuous positive airway pressure (CPAP) therapy and whether this treatment is required every night.125 OSA patients with an original oxygen desaturation index (ODI) >10 events per hour, established on CPAP, were asked to withdraw CPAP for four nights and performed ambulatory nocturnal pulse oximetry on the fourth night of CPAP withdrawal. An ODI >10 events per hour during pulse oximetry was considered to indicate persistent OSA. Patients not experiencing recurrence of OSA underwent repeat ambulatory pulse oximetry after a further 2-week period off CPAP.In 71% of the patients, OSA recurred after four nights of CPAP withdrawal (group 1); thus, OSA did not recur in 29% (group 2). 55% of group 2 had an ODI >10 events per hour after 2 weeks off CPAP; thus, 45% remained without a recurrence. In multivariate analysis, higher original ODI, longer duration of CPAP therapy, current smoking status and larger neck circumference were independently associated with a higher ODI after four nights of CPAP withdrawal (all p<0.05).Following CPAP withdrawal, a third of CPAP-treated patients do not experience significant recurrence of oxygen desaturations after 4 days and ∼10% do not after 2 weeks. Thus, a significant proportion of patients may be able to stop CPAP for short periods.
    European Respiratory Journal 01/2014; 43(5). DOI:10.1183/09031936.00180213 · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments, we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. This was a randomized, placebo-controlled, double-blind, three period cross-over trial. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients, 16 with pulmonary arterial PH, 7 with chronic thromboembolic PH, and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD), SF-36 quality of life, polysomnography, and echocardiography. Medians (quartiles) of the 6 MWD after NOT, acetazolamide, and placebo were 480 m (390;528), 440 m (368;468), and 454 m (367;510), respectively, mean differences: NOT vs. placebo +25 m (95% CI 3-46, P= 0.027), acetazolamide vs. placebo -9 m (-34-17, P = 0.223), and NOT vs. acetazolamide +33 (12-45, P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). In patients with pre-capillary PH and SDB on optimized pharmacological therapy, NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. NTC01427192.
    European Heart Journal 12/2013; DOI:10.1093/eurheartj/eht540 · 14.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep. Fourty-four healthy men (mean age 25.0±5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design. Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8-4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (∼4% at 1630 m and 15% at 2590 m), while theta activity (4.6-8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4-8 Hz and 13-14.4 Hz) and breathing variables (AHI, ODI; 0.8-4.6 Hz). The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.
    PLoS ONE 10/2013; 8(10):e76945. DOI:10.1371/journal.pone.0076945 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Pichler Hefti, Jacqueline, Denise Sonntag, Urs Hefti, Lorenz Risch, Otto D. Schoch, Alexander J. Turk, Thomas Hess, Konrad E Bloch, Marco Maggiorini, Tobias M. Merz, Klaus M. Weinberger, and Andreas R. Huber. Oxidative stress in hypobaric hypoxia and influence on vessel-tone modifying mediators. High Alt Med Biol. 14:273-279, 2013.-Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.
    High altitude medicine & biology 09/2013; 14(3):273-9. DOI:10.1089/ham.2012.1110 · 1.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference -0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. ClinicalTrials.gov NCT01130948.
    PLoS ONE 08/2013; 8(8):e70081. DOI:10.1371/journal.pone.0070081 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: The aim of this study was to test the effectiveness of Provent, an expiratory nasal resistance valve, to prevent the recurrence of OSA following CPAP withdrawal. DESIGN: Randomised, partially blinded, parallel, placebo-controlled trial. SETTING: Outpatient sleep clinics in the UK (Oxford) and Switzerland (Zurich). PARTICIPANTS: 67 patients with OSA receiving CPAP were randomised to one of three groups for 2 weeks: continuing CPAP, Provent or placebo Provent. MAIN OUTCOME MEASURES: Primary outcomes included for Provent versus placebo Provent, OSA severity (oxygen desaturation index (ODI), apnoea-hypopnoea index (AHI)) and Epworth Sleepiness Scale (ESS) score. Secondary outcomes for Provent versus placebo Provent included ODI from ambulatory pulse oximetry and blood pressure (BP). For CPAP versus Provent, or CPAP versus placebo Provent, secondary outcomes included ODI/AHI, ESS and BP. RESULTS: 63 patients were included in the per protocol analysis. OSA recurred in the Provent (ODI 35.8, SD 17.4) and placebo Provent (ODI 28.2, SD 18.3) groups, and there was no significant difference in ODI, AHI and ESS between Provent and placebo Provent at 2 weeks (mean difference ODI -1.0, 95% CI -10.0 to +12.0, p=0.85; AHI +3.2, 95% CI -7.7 to +14.1, p=0.52; and ESS -1.4, 95% CI -4.1 to +1.4, p=0.33). ODI from ambulatory pulse-oximetry and BP at 2 weeks were not different in the Provent versus placebo Provent groups. ODI, AHI and BP, but not ESS, were significantly higher in the Provent and placebo Provent groups compared with CPAP. CONCLUSIONS: Provent cannot be recommended as an alternative short-term therapy for patients with moderate to severe OSA already on CPAP. TRIALREGNO: NCT01332175.
    Thorax 05/2013; 68(9). DOI:10.1136/thoraxjnl-2013-203508 · 8.56 Impact Factor

Publication Stats

3k Citations
887.54 Total Impact Points


  • 1991–2014
    • University of Zurich
      • • Internal Medicine Unit
      • • Ophthalmology Unit
      • • Pneumologie
      Zürich, Zurich, Switzerland
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 1997–2009
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 1994
    • University of Miami
      كورال غيبلز، فلوريدا, Florida, United States