Blood pressure response to exposure to moderate altitude in patients with COPD

Esther I Schwarz,1 Tsogyal D Latshang,1 Michael Furian,1 Deborah Flück,1 Sebastian Segitz,1 Severine Müller-Mottet,1 Silvia Ulrich,1 Konrad E Bloch,1,2 Malcolm Kohler1,2 1Department of Pulmonology and Sleep Disorders Centre, University Hospital of Zurich, Zurich, Switzerland; 2Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland Purpose: Patients with COPD might be particularly susceptible to hypoxia-induced autonomic dysregulation. Decreased baroreflex sensitivity (BRS) and increased blood pressure (BP) variability (BPV) are markers of impaired cardiovascular autonomic regulation and there is evidence for an association between decreased BRS/increased BPV and high cardiovascular risk. The aim of this study was to evaluate the effect of short-term exposure to moderate altitude on BP and measures of cardiovascular autonomic regulation in COPD patients. Materials and methods: Continuous morning beat-to-beat BP was noninvasively measured with a Finometer® device for 10 minutes at low altitude (490 m, Zurich, Switzerland) and for 2 days at moderate altitude (2,590 m, Davos Jakobshorn, Switzerland) – the order of altitude exposure was randomized. Outcomes of interest were mean SBP and DBP, BPV expressed as the coefficient of variation (CV), and spontaneous BRS. Changes between low altitude and day 1 and day 2 at moderate altitude were assessed by ANOVA for repeated measurements with Fisher’s exact test analysis. Results: Thirty-seven patients with moderate to severe COPD (mean±SD age 64±6 years, FEV1 60%±17%) were included. Morning SBP increased by +10.8 mmHg (95% CI: 4.7–17.0, P=0.001) and morning DBP by +5.0 mmHg (95% CI: 0.8–9.3, P=0.02) in response to altitude exposure. BRS significantly decreased (P=0.03), whereas BPV significantly and progressively increased (P<0.001) upon exposure to altitude. Conclusion: Exposure of COPD patients to moderate altitude is associated with a clinically relevant increase in BP, which seems to be related to autonomic dysregulation. Clinical trial registration: ClinicalTrials.gov (NCT01875133). Keywords: COPD, hypobaric hypoxia, baroreflex sensitivity, blood pressure variabilit

Effect of oxygen and acetazolamide on nocturnal cardiac conduction, repolarization, and arrhythmias in precapillary pulmonary hypertension and sleep-disturbed breathing

BACKGROUND: Sleep-disturbed breathing (SDB) is common in patients with precapillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB in patients with PH, 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, crossover trial, 23 patients with arterial (n = 16) or chronic thromboembolic PH (n = 7) and SDB defined as a mean nocturnal oxygen saturation 3%) > 10/h with daytime Pao2 ≥ 7.3 kPa were studied. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo each during 1 week separated by a 1-week washout period. Three-lead ECG 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 beats/min vs 72 ± 9 beats/min, P = .010) and early morning heart rate compared with placebo. At late evening, the heart rate-adjusted PQ time was increased under acetazolamide compared with placebo (mean difference, 10 milliseconds; 95% CI, 0-20 milliseconds; P = .042). In the morning under NOT, the heart rate-adjusted QT (QTc) interval was decreased compared with placebo (mean difference, -25 milliseconds; 95% CI, -45 to -6 milliseconds; P = .007), and the interval between the peak and the end of the T wave on the ECG was shorter compared with acetazolamide (mean difference, -11 milliseconds; 95% CI, -21 to -1 milliseconds; P = .028). Arrhythmias were rare and similar with all treatments. CONCLUSIONS: In patients with PH with SDB, NOT reduces nocturnal heart rate and QTc in the morning, thus, favorably modifying prognostic markers. TRIAL REGISTRY: ClinicalTrials.gov; No.: NTC-01427192; URL: www.clinicaltrials.gov

Lebensqualität bei pulmonal arterieller und chronisch thromboembolischer pulmonaler Hypertonie

Die Lebensqualität (Quality of life, QoL) im Allgemeinen und die gesundheitsbezogene Lebensqualität („Health-related QoL; HRQOL) im Besonderen rücken aktuell immer mehr in den Fokus des Interesse bei chronischen Krankheiten und somit auch für Patienten mit einer pulmonal-arteriellen Hypertonie (PAH) oder chronisch thromboembolischen pulmonalen Hypertonie (CTEPH). Es gibt Überlegungen, diese als primäre oder ko-primäre Outcome-Parameter in Studien einzusetzen. Die Erfassung der QoL/HRQOL und die Objektivierung klinisch relevanter Veränderungen dieser ist allerdings nicht trivial. Diese Übersichtsarbeit beleuchtet sowohl die allgemeinen Aspekte der Evaluation der HRQOL als auch die Vor- und Nachteile der hierbei aktuell verwendeten Instrumente. Assessments of general quality of life (QoL) and health-related quality of life (HRQOL) are increasingly important in the care of patients with chronic diseases including pulmonary arterial and chronic thromboembolic pulmonary hypertension and are under consideration as important endpoint of clinical trials and drug registration. The assessment of quality of life is not trivial. This review outlines the assets and pitfalls of general aspects of HRQOL and instruments used in PH

On the role of mechanical stress in the chemical ordering of nanoalloys

Metallic alloy clusters at equilibrium display an inhomogeneous stress field which may contribute to the chemical ordering and segregation properties. We use the example of cuboctahedral and icosahedral Au-Pd clusters with the same size to compare these properties in systems displaying moderately and highly inhomogeneous stress fields. Metropolis Monte Carlo simulations in the semi-grand canonical ensemble are used with an empirical potential to predict equilibrium configurations. Pressure maps are used to estimate stress on each atom. It is found that when the stress field is moderately inhomogeneous, ordering is dominantly driven by thermodynamic forces. In icosahedral clusters, ordering is found to be the consequence of a balance where thermodynamic forces and mechanical stress may conflict or reinforce each other. Order-disorder transitions are smoother in the systems with higher stress inhomogeneity and it is conjectured that, in icosahedral clusters, disorder may nucleate in the central core. © EDP Sciences, Società Italiana di Fisica, Springer-Verlag 2012.SCOPUS: ar.jinfo:eu-repo/semantics/inPres