Annette Schneider

Sleep-related hypoxaemia and excessive erythrocytosis in Andean high-altitude natives

To determine whether nocturnal hypoxaemia contributes to the excessive erythrocytosis (EE) in Andean natives, standard polysomnographies were performed in 10 patients with EE and in 10 controls (mean haematocrit 76.6±1.3% and 54.4±0.8%, respectively) living at an altitude of 4,380 m. In addition, the effect of O2 administration for 1 h prior to sleep, and the relationship between the hypoxic/hypercapnic ventilatory response and the apnoea/hypopnoea index (AHI) during sleep were studied. Awake arterial oxygen saturation (Sa,O2) was significantly lower in patients with EEthan in controls (83.7±0.3% versus 85.6±0.4%). In both groups, the mean Sa,O2 significantly decreased during sleep (to 80.0±0.8% in EE and to 82.8±0.5% in controls). The mean Sa,O2 values remained significantly lower in patients with EE than in controls at all times of the night, and patients with EE spent significantly more time than the controls with an Sa,O2 of <80%. There were no differences between the two groups in the number and duration of the apnoeas/hypopnoeas. None of these variables were affected by O2 administration. In both groups the AHI positively correlated with the hypercapnic ventilatory response. Andean natives undergo minor respiratory disorders during sleep. The reduction inoxygen saturation found in subjects with excessive erythrocytosis was small, yet consistent and potentially important, as it remained below the threshold known for theincrease in erythropoietin stimulation. This may be an important factor promoting erythropoiesis, but its relevance needs to be further explored.

Ventilation, Autonomic Function, Sleep and Erythropoietin

Polycythemia is one of the key factors involved in the chronic mountain sickness syndrome, a condition frequent in Andean natives but whose causes still remain unclear. In theory, polycythemia may be secondary to abnormalities in ventilation, occurring during day or night (e.g. due to sleep abnormalities) stimulating excessive erythropoietin (Epo) production, or else it may result from either autogenous production, or from co-factors like cobalt. To assess the importance of these points, we studied subjects with or without polycythemia, born and living in Cerro de Pasco (Peru, 4330m asl, CP) and evaluated the relationship between Epo and respiratory variables both in CP and sea level. We also assessed the relationship between sleep abnormalities and the circadian rhythm of Epo. Polycythemic subjects showed higher Epo in all conditions, lower SaO2 and hypoxic ventilatory response, higher physiological dead space and higher CO2, suggesting ventilatory inefficiency. Epo levels could be highly modified by the level of oxygenation, and were related to similar directional changes in SaO2. Cobalt levels were normal in all subjects and correlated poorly with hematologic variables. The diurnal variations in Epo were grossly abnormal in polycythemic subjects, with complete loss of the circadian rhythm. These abnormalities correlated with the levels of hypoxemia during the night, but not with sleep abnormalities, which were only minor even in polycythemic subjects. The increased Epo production is mainly related to a greater ventilatory inefficiency, and not to altered sensitivity to hypoxia, cobalt or sleep abnormalities. Improving oxygenation can represent a possible therapeutic option for this syndrome.

Peripheral arterial vascular function at altitude: sea-level natives versus Himalayan high-altitude natives.

Objectives Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5050 m. Methods We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance. Results Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 ± 2.5 versus 3.8 ± 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high-altitude than in the sea-level natives at low frequencies (28 ± 12 versus 6.4 ± 20% at 2 Hz, P < 0.01). Conclusions Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function.

Dynamic cardiocirculatory control during propofol anesthesia in mechanically ventilated patients.

We evaluated dynamic cardiovascular control by spectral analytical methods in 20 young adults anesthetized with propofol (2.5 mg/kg, followed by continuous infusion of 0.1 mg/kg/min) and in an awake control group during cyclic stimulation of the carotid baroreceptors via sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and at 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity). During anesthesia and mechanical ventilation at 0.25 Hz, major underdampened hemodynamic oscillations occurred at 0.055 ± 0.012 Hz. The response of RR intervals to baroreceptor stimulation at 0.2 Hz was markedly decreased during anesthesia (median of transfer function magnitude between neck suction and RR intervals 3% of the awake control). Blood pressure response to baroreceptor stimulation at 0.1 Hz was significantly decreased during anesthesia to 26% (systolic blood pressure), and 44% (diastolic blood pressure) of the awake control. There was a significant delay in baroreflex effector responses during anesthesia. Our results demonstrate a markedly depressed vagally mediated heart rate response and an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia in mechanically ventilated patients. The disturbed baroreflex control is accompanied by an irregular dynamic behavior of cardiovascular regulation, indicating a decreased stability of the control system. Implications An irregular dynamic behavior of the cardiovascular control system, associated with an impaired baroreflex control of heart rate and blood pressure, can be observed during propofol anesthesia in mechanically ventilated subjects.

Sinusoidal neck suction for evaluation of baroreflex sensitivity during desflurane and sevoflurane anesthesia.

Sevoflurane and desflurane modulate autonomic nervous activity by different mechanisms. We tested the hypothesis that these anesthetics also exhibit different effects on short-term baroreflex regulation of arterial blood pressure. Forty ASA physical status I patients, aged 20 to 42 yr, were randomly assigned to receive either 1.0 minimum alveolar anesthetic concentration of sevoflurane or desflurane for the maintenance of anesthesia. Patients were studied during awake conditions and 20 min after the anesthesia induction using sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity), whereas respiratory frequency was fixed at 0.25 Hz. RR interval and arterial blood pressure responses were evaluated by power spectral analysis and complex transfer function analysis. Sevoflurane and desflurane did not disturb the linear relationship between baroreceptor stimulation and effector response, expressed as squared coherence of signals, i.e., the equivalent of the correlation coefficient of power spectra. Sevoflurane and desflurane depressed the response of the heart rate to neck suction in a similar way without affecting the time delay between baroreceptor stimulation and vagal-mediated cardiac response. The gain of the transfer function between neck suction and oscillation in arterial blood pressure at 0.1 Hz decreased with sevoflurane and desflurane to comparable values. Both anesthetics increased the delay of systolic blood pressure response to baroreceptor stimulation from approximately 3.5 to 4.3 s. Baroreflex-mediated short-term control of arterial blood pressure is similar between desflurane and sevoflurane during steady-state conditions.

In vitro effects of fluoride on pseudocholinesterase activity and the metabolism of the cis-trans and trans-trans isomers of mivacurium.

IN vitro experiments at room temperature with benzoylcholine as a substrate showed that 10–50 mM fluoride, the concentration usually observed with sevoflurane anesthesia, inhibits pseudocholinesterase (PChE) by 16– 56%. PChE is the enzyme responsible for the metabolism of mivacurium. Mivacurium dose requirements to maintain neuromuscular blockade are decreased by sevoflurane. In addition to the well-known potentiation of nondepolarizing neuromuscular blocking agents by volatile anesthetics, this might be caused by an inhibition of PChE. The aim of this study was to investigate whether fluoride concentrations between 10 and 1,000 mM inhibit PChE at 37°C using butyrylthiocholine and mivacurium as substrates.

Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas

Abstract This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.