Assessment of the impact of 10-day intermittent hypoxia on the autonomic control measured by heart rate variability.

PURPOSE: The purpose of this study is to establish the alterations in the activity of the autonomic nervous system (ANS) via heart rate variability (HRV) in subjects exposed to 1 h of exogenous hypoxia for 10 consecutive days. METHODS: Twelve healthy non-smoker males at mean age of 29.8 ± 7.4 (mean ± SD) breathed hypoxic air delivered through hypoxicator (FiО2 = 12.3% ± 1.5%) for 1 h in 10 consecutive days. Pulse oximetry and electrocardiography were monitored during the visit and HRV was calculated for the entire 1-h hypoxic period. RESULTS: Comparing the last hypoxic visit to the first, subjects had higher standard deviation of normal-to-normal interbeat intervals (SDNNs) (65.7 ± 32.5 vs. 81.1 ± 32.0 ms, p = 0.013) and root mean square of successive R-R interval difference (RMSSD) (58.1 ± 30.9 vs. 76.5 ± 34.6 ms, p = 0.029) as well as higher lnTotal power (8.1 ± 1.1 vs. 8.5 ± 0.9 ms2, p = 0.015) and high frequency (lnHF) (6.8 ± 1.3 vs. 7.5 ± 1.2 ms2, p = 0.05) and lower LF/HF (2.4 ± 1.4 vs. 1.5 ± 1.0, p = 0.026). Changes in saturation (87.0 ± 7.1 vs. 90.8 ± 5.0%, p = 0.039) and heart rate (67.1 ± 8.9 vs. 62.5 ± 6.0 beats/min, p = 0.040) were also observed. CONCLUSIONS: Intermittent hypoxic training consisting of 1-h hypoxic exposure for 10 consecutive days could diminish the effects of acute exogenous hypoxia on the ANS characterized by an increased autonomic control (SDNN and total power) with augmentation of the parasympathetic nervous system activity (increased RMSSD and HF and decreased LF/HF). Therefore, it could be applied as a pre-acclimatization technique aiming at an increase in the autonomic control and oxygen saturation in subjects with upcoming sojourn to high altitude.

Central Sleep Apnea with Cheyne-Stokes Breathing in Heart Failure - From Research to Clinical Practice and Beyond.

Characterized by periodic crescendo-decrescendo pattern of breathing alternating with central apneas, Central sleep apnea (CSA) with Cheyne-Stokes Breathing represents a highly prevalent, yet underdiagnosed comorbidity in chronic heart failure (CHF). A diverse body of evidence demonstrates increased morbidity and mortality in the presence of CSB. CSB has been described in both CHF patients with preserved and reduced ejection fraction, regardless of drug treatment. Risk factors for CSB are older age, male gender, high BMI, atrial fibrillation and hypocapnia.The pathophysiology of CSB has been explained by the loop gain theory, where a controller (the respiratory center) and a plant (the lungs) are operating in a reciprocal relationship (negative feedback) to regulate a key parameter (partial pressure of carbon dioxide (pCO2)). The temporal interaction between these elements is dependent on the circulatory delay. Increased chemosensitivity/chemoresponsiveness of the respiratory center and/or augmented ascending non- CO2 stimuli from the C-fibers in the lungs (interstitial pulmonary edema), overly efficient ventilation when breathing at low volumes and prolonged circulation time are involved. An alternative hypothesis of CSB being an adaptive response of the failing heart has its merits as well. The clinical manifestation of CSB is usually poor, lacking striking symptoms and complaints. Witnessed apneas and snoring are infrequently reported by the sleep partner. Sometimes patients may report poor sleep quality with frequent awakenings, paroxysmal nocturnal dyspnea and frequent urination at night. Standard instrumental and laboratory studies, performed in CHF patients, may present clues to the presence of CSB. Concentric remodeling of the left ventricle and dilated left atrium (echocardiography), high BNP and C-reactive protein levels, increased ventilation-carbon dioxide output (VEVCO2) and lower end-tidal CO2 (cardiopulmonary exercise testing), reduced diffusion capacity (pulmonary function testing) and hypocapnia (blood-gas analysis) may indicate the presence of CSB.CSB and cardiovascular disease are probably linked through bidirectional causality. Cyclic variations in heart rate, blood pressure, respiratory volume, partial pressure of arterial oxygen (pO2) and pCO2 lead to sympathetic-adrenal activation. The latter worsens ventricular energetism and survival of cardiomyocytes and exerts antiarhythmogenic effects. It causes cardiac remodeling, potentiating the progression and the lethal outcome in CHF patients. Several treatment modalities have been proposed in CSB. The most commonly used are continuous positive airway pressure (CPAP), adaptive servoventilation (ASV) and nocturnal home oxygen therapy (HOT). Novel therapies like nocturnal supplemental CO2 and phrenic nerve stimulation are being tested recently. The current treatment recommendations (by the American Academy of Sleep Medicine) are for CPAP and HOT as standard therapies, while ASV is an option only in patients with EF > 45%. BPAP (bilevel device) remains an option only when there is no adequate response to previous modes of treatment. Acetazolamide and theophylline are options only after failing the above modalities and if accompanied by a close follow-up.

Exercise performance and ventilatory efficiency in patients with mild and moderate liver cirrhosis.

1. The impact of ventilatory efficiency on reduced exercise capacity and recovery oxygen kinetics has not been addressed in cirrhotic patients. The aim of the present study was to investigate exercise performance and ventilatory efficiency in patients with mild and moderate liver cirrhosis (LC). 2. Nineteen male non-hypoxic patients with LC (age 51.3 +/- 9.1 years; body mass index (BMI) 25.6 +/- 3.6 kg/m(2)) classified by the Child-Pugh score as class A (n = 7) and class B (n = 12) and 19 age- and BMI-matched controls participated in the study. Subjects undertook maximal incremental exercise testing on a treadmill using the Bruce protocol. 3. Patients with LC showed a reduced diffusion capacity (D(L,CO)%) compared with controls (74.6 +/- 15.2 vs 95.6 +/- 12.9%, respectively; P < 0.001), but a comparable volume standardized diffusion coefficient (1.33 +/- 0.22 vs 1.45 +/- 0.18 mmol/min per kPa per L, respectively; P = 0.74). Patients with LC had a significantly lower exercise capacity compared with controls (VO(2 max) 23.8 +/- 3.8 vs 30.6 +/- 4.4 mL/min per kg, respectively; P < 0.001). Recovery oxygen kinetics were also impaired in LC patients compared with controls (104.6 +/- 19.3 vs 84.4 +/- 22.7 s, respectively; P = 0.012). The chronotropic index was significantly lower in the LC group compared with controls (0.67 +/- 0.19 vs 0.82 +/- 0.17, respectively; P = 0.030) and LC patients showed higher ventilatory equivalents (30.4 +/- 3.8 vs 26.3 +/- 2.3, respectively; P < 0.001) and lower oxygen uptake efficiency slope values (2187 +/- 445 vs 2745 +/- 473 mL/min per log(10)L, respectively; P < 0.001) compared with controls, which is indicative of decreased ventilatory efficiency. Patients with LC also had a higher standardized maximal exercise perception score (SMEPS) compared with controls (0.62 +/- 0.18 vs 0.46 +/- 0.15, respectively; P = 0.011). Moderate negative correlations were found between Child-Pugh score and VO(2 max)% (r = -0.496; P = 0.031). 4. In conclusion, patients with mild and moderate LC have reduced exercise capacity, which correlates with Child-Pugh score, as well as reduced chronotropic index and prolonged recovery oxygen uptake kinetics. The results suggest worsened ventilatory efficiency during exercise and cardiopulmonary reasons for the higher SMEPS in these patients.

Possible mechanism of action of vanadium ions as an antidiabetic agent.

Vanadium compounds, at much higher concentrations than they are typically ingested, are being considered for use in the treatment of diabetes mellitus. They exert an insulin-mimetic effect in an insulin-receptor-independent manner. In our study we obtained new data about the vanadium insulin-receptor-independent mechanism of action on cell membranes. When rat stomach smooth muscle samples are treated with NH4VO3 (10(-7) divided by 10(-5) this action is possibly exhibited with increased influx of Ca2+ through VDCa2+C.