Impact of Moderate Altitude on Pro-Inflammatory Cytokines in Healthy Volunteers.

BACKGROUND: The induction of microvascular inflammation and the effects on cytokine production in blood due to hypoxia has been shown in the past. We have previously reported a statistically significant increase of the pro-inflammatory cytokine interleukin-8 (IL-8) in normobaric hypoxia in the setting of a hypoxia-chamber. In the present study, we sought to analyze plasma levels of inflammatory cytokines in a real-life stetting in order to foster our knowledge on hypoxia induced microvascular inflammation at moderate altitude. METHODS: Pro-inflammatory cytokines (IL-8, IL-6, TNF-α) were measured in an experimental field study, exposing 18 healthy volunteers to moderate hypoxia while staying at a mountain lodge in Diavolezza, Switzerland (2978 meters above sea level). Plasma cytokine levels were measured by ELISA. RESULTS: In contradiction to our results in a normobaric hypoxia-chamber, exposure to moderate hypoxia led to a significant decrease of plasma IL-8 levels in a real-life setting (from 2.902 (1.046 - 4.984) pg/mL to 1.395 (0.698 - 3.712) pg/mL, p = 0.034). Concentrations of IL-6 and TNF-α did not show statistically significant changes in comparison to baseline measurements. CONCLUSIONS: The results of this study show a decrease of proinflammatory cytokine IL-8 in a real life setting of moderate altitude in healthy individuals. Initiation of angiogenesis or subliminal stimulus for an altitude-induced inflammatory reaction may be explanations for this unexpected finding.

Prognostic relevance of heart rate at rest for survival and the quality of life in patients with dilated cardiomyopathy.

OBJECTIVES: Reduction of resting heart rate (HR) has been suggested as a novel therapeutic approach in patients with chronic heart failure because it has been shown to prolong survival and also to improve health-related quality of life (Hr-QoL). The purpose of this analysis was to assess the prognostic impact of resting HR in patients with dilated cardiomyopathy (DCM). METHODS: 217 patients with DCM confirmed by endomyocardial biopsy were investigated (age 49 ± 11 years, 20.7 % were female). The study population was divided into two groups according to the median of the resting HR. After a median follow-up time of 7.4 years overall survival and health-related quality of life (Hr-QoL) were compared in both groups. Survival was compared using Kaplan-Meier method and Hr-QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: Elevated resting HR was associated with poor 1-year survival (p = 0.03). In contrast, long-term survival was not affected by HR (p = 0.20). Patients with lower HR at rest scored significantly lower on the MLHFQ (20 vs. 36, p = 0.03), indicating that higher resting HR is associated with an impairment of Hr-QoL. CONCLUSIONS: Increased HR might be used as a diagnostic tool to identify patients at risk. Reduction of resting HR in patients with DCM might be a therapeutic option to improve Hr-QoL and therefore merits further investigation in future studies.

Impact of short-term systemic hypoxia on phagocytosis, cytokine production, and transcription factor activation in peripheral blood cells.

Hypoxia frequently associated with certain physiologic and pathologic conditions influences numerous cellular functions. Because the effects of short-term hypoxia are incompletely understood, we examined phagocytosis and cytokine production as well as the activation of the transcription factors HIF-1 and NFκB in peripheral blood cells of healthy volunteers exposed to an oxygen concentration equivalent to that found at a height of 5500 m. Furthermore, we analysed plasma HIF-1 and serum concentrations of various HIF-1-dependent genes. Results showed that short-term hypoxia increased phagocytosis in neutrophils without affecting monocyte phagocytosis. Hypoxia decreased basal TNFα concentration in monocytes and basal interferon γ concentration in CD4(+) T lymphocytes. In contrast, plasma HIF and serum VEGF concentrations were not affected by hypoxia, although serum EPO concentration was raised. In PBMC, hypoxia increased cytosolic HIF-1 concentration without affecting nuclear HIF-1 concentration and led to a rise in the nuclear NFκB in PBMC. Our results show that short-term hypoxia affects immune functions in healthy individuals. Furthermore, we speculate that the effects of hypoxia are not due to HIF-1, but are caused by the activation of NFκB .

Endovascular treatment of superior vena cava syndrome by percutaneous venoplasty.

Thrombosis of the superior vena cava leads to obstruction of venous outflow of the head and upper extremities and causes severe clinical symptoms. The management of SVC syndrome depends on aetiology and acuity at clinical presentation and ranges from conservative medical treatment to bypass surgery. Endovascular treatment can provide rapid relief of symptoms and substantial clinical improvement independent of aetiology. We report a case of successful interventional treatment in a patient with catheter-induced SVC thrombosis and present a review of the literature.