Increased myocardial blood flow during acute exposure to simulated altitudes.

BACKGROUND: Although only poor data exist on changes in myocardial blood flow (MBF) under acute hypoxia, patients with known coronary artery disease are advised not to exceed a moderate altitude exposure of about 2000 m above sea level. METHODS AND RESULTS: We measured MBF with positron emission tomography using O-15--labeled water in 8 healthy human volunteers (aged 26 +/- 3 years [mean +/- SD]) at baseline (450 m above sea level, Zurich, Switzerland) and during acute hypoxic hypoxemia induced by inhalation of 2 hypoxic gas mixtures corresponding to altitudes of 2000 and 4500 m. MBF remained unchanged at 2000 m (increase of 10%, not significant) but increased significantly at 4500 m (62%, P <.001), exceeding the relative increase in rate pressure product. CONCLUSIONS: Our results may explain why exposure to an altitude of 2000 m (corresponding to the cabin pressure in most airplanes during flight) is clinically well tolerated, even by patients with reduced coronary flow reserve, such as those with coronary artery disease. However, at an altitude of 4500 m, MBF increases significantly, supporting the recommendation that patients with impaired flow reserve avoid exposure to higher altitudes.

Effects of hypobaric hypoxia on vascular endothelial growth factor and the acute phase response in subjects who are susceptible to high-altitude pulmonary oedema.

In order to investigate whether vascular endothelial growth factor (VEGF) and inflammatory pathways are activated during acute hypobaric hypoxia in subjects who are susceptible to high-altitude pulmonary oedema (HAPE-S), seven HAPE-S and five control subjects were exposed to simulated altitude corresponding to 4000 m in a hypobaric chamber for 1 day. Peripheral venous blood was taken at 450 m (Zürich level) and at 4000 m, and levels of erythropoietin (EPO), VEGF, interleukin-6 (IL-6) and the acute-phase proteins complement C3 (C3), alpha1-antitrypsin (alpha1AT), transferrin (Tf) and C-reactive protein (CRP) were measured. Peripheral arterial oxygen saturation (SaO2) was recorded. Chest radiography was performed before and immediately after the experiment. EPO increased during altitude exposure, correlating with SaO2, in both groups (r = -0.86, P < 0.001). Venous serum VEGF did not show any elevation despite a marked decrease in SaO2 in the HAPE-S subjects [mean (SD) HAPE-S: 69.6 (9.1)%; controls: 78.7 (5.2)%]. C3 and alpha1AT levels increased in HAPE-S during hypobaric hypoxia [from 0.94 (0.11) g/l to 1.07 (0.13) g/l, and from 1.16 (0.08) g/l to 1.49 (0.27) g/l, respectively; P < 0.05], but remained within the clinical reference ranges. No significant elevations of IL-6, Tf or CRP were observed in either group. The post-exposure chest radiography revealed no signs of oedema. We conclude that VEGF is not up-regulated in HAPE-S and thus does not seem to increase critically pulmonary vascular permeability during the 1st day at high altitude. Furthermore, our data provide evidence against a clinically relevant inflammation in the initial phase of exposure to hypoxia in HAPE-S, although C3 and alpha1AT are mildly induced.

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature.

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients.

A role for GH in the pathogenesis of diabetic retinopathy has long been postulated. Previous clinical studies, however, have been confounded by hyperglycemia. We have identified 2 cases of retinopathy associated with exogenous GH therapy in nondiabetic patients. Cases were identified through the MedWatch drug surveillance system of the U.S. Food and Drug Administration. Causality by concomitant medications was excluded by a search of the literature and the FDA data base. The first patient, an obese, 31-yr-old male with traumatic hypothalamic injury, presented with nonproliferative retinopathy and macular edema, resulting in decreased visual acuity (OD 20/40-1; OS count fingers), which required laser surgery. Human GH had been initiated at 0.009 mg/ kg.day, 14 months earlier, and titrated to 0.017 mg/kg.day. The second patient, a nonobese, 11-yr-old girl receiving GH for the management of short stature in Turner's Syndrome, presented with neovascularization. GH doses were 0.033 mg/kg.day for the first 17 months and 0.043 mg/ kg.day for the following 5 months. Cumulative laboratory and clinical observations suggest that GH and related peptides have a role in retinal pathology independent of the degree of glucose tolerance.

Papilledema in 15 renally compromised patients treated with growth hormone.

Intracranial hypertension with papilledema has been reported in renal patients, but a survey of the literature suggests that the incidence rate is low. We present reports of 15 of approximately 1,670 patients with renal disorders, who were treated with growth hormone for impaired growth and subsequently developed symptoms and/or signs of intracranial hypertension. The male:female ratio was 6.5:1, and the median age was 12 years. The median duration of growth hormone treatment before onset of symptoms or signs was 13 weeks. All but 2 patients were symptomatic. In the patients in whom growth hormone therapy is known to have been discontinued, the symptoms and signs of intracranial hypertension abated. At least 4 of these patients experienced a recurrence when re-exposed to growth hormone. Many of the affected patients presented with predisposing conditions, but growth hormone appears to have been the precipitating factor. Prospective funduscopic evaluation may be warranted in patients with renal disorders who are receiving growth hormone.

Volume changes in the forearm and lower limbs during 2 h of acute hypobaric hypoxia in nonacclimatized subjects.

To investigate the role of fluid shifts during the short-term adjustment to acute hypobaric hypoxia (AHH), the changes in lower limb (LV) and forearm volumes (FV) were measured using a strain-gauge plethysmograph technique in ten healthy volunteers exposed to different altitudes (450 m, 2500 m, 3500 m, 4500 m) in a hypobaric chamber. Arterial blood pressure, heart rate, arterial oxygen saturation (SaO2), endtidal gases, minute ventilation and urine flow were also determined. A control experiment was performed with an analogous protocol under normobaric normoxic conditions. The results showed mean decreases both in LV and FV of 0.52 (SD 0.39) ml x 100 ml(-1) and -0.65 (SD 0.32) ml x 100 ml(-1), respectively, in the hypoxia experiments [controls: LV 0.28 (SD 0.37), FV 0.41 (SD 0.47) ml x 100 ml(-1)]. Descent to normoxia resulted in further small but not significant decreases in mean LV [-0.02 (SD 0.11) ml x 100 ml(-1)], whereas mean FV tended to increase slightly [ + 0.02 (SD 0.14) ml x 100 ml(-1)]; in the control experiments mean LV and FV decreased continuously during the corresponding times [-0.19 (SD 0.31), -0.18 (SD 0.10) ml x 100 ml(-1) , respectively]. During the whole AHH, mean urine flow increased significantly from 0.84 (SD 0.41) ml x min(-1) to 3.29 (SD 1.43) ml x min(-1) in contrast to the control conditions. We concluded that peripheral fluid volume shifts form a part of the hypoxia-induced acute cardiovascular changes at high altitude. In contrast to the often reported formation of peripheral oedema after prolonged exposure to hypobaric hypoxia, the results provided no evidence for the development of peripheral oedema during acute induction to high altitude. However, the marked increase in interindividual variance in SaO2 and urine flow points to the appearance of the first differences in the short-term adjustment even after 2 h of acute hypobaric hypoxia.

Effect of exercise-induced hyperventilation on airway resistance and cycling endurance.

The purpose of the present study was to investigate the effect of exercise induced hyperventilation and hypocapnia on airway resistance (Raw), and to try to answer the question whether a reduction of Raw is a mechanism contributing to the increase of endurance time associated with a reduction of exercise induced hyperventilation as for example has been observed after respiratory training. Eight healthy volunteers of both sexes participated in the study. Cycling endurance tests (CET) at 223 (SD 47) W, i.e. at 74 (SD 5)% of the subject's peak exercise intensity, breathing endurance tests and body plethysmograph measurements of pre- and postexercise Raw were carried out before and after a 4-week period of respiratory training. In one of the two CET before the respiratory training CO2 was added to the inspired air to keep its end-tidal concentration at 5.4% to avoid hyperventilatory hypocapnia (CO2-test); the other test was the control. The pre-exercise values of specific expiratory Raw were 8.1 (SD 2.8), 6.8 (SD 2.6) and 8.0 (SD 2.1) cm H2O.s and the postexercise values were 8.5 (SD 2.6), 7.4 (SD 1.9) and 8.0 (SD 2.7) cm H2O.s for control CET, CO2-CET and CET after respiratory training, respectively, all differences between these tests being nonsignificant. The respiratory training significantly increased the respiratory endurance time during breathing of 70% of maximal voluntary ventilation from 5.8 (SD 2.9) min to 26.7 (SD 12.5) min. Mean values of the cycling endurance time (tcend) were 22.7 (SD 6.5) min in the control, 19.4 (SD 5.4) min in the CO2-test and 18.4 (SD 6.0) min after respiratory training. Mean values of ventilation (VE) during the last 3 min of CET were 123 (SD 35.8) l.min-1 in the control, 133.5 (SD 35.1) l.min-1 in the CO2-test and 130.9 (SD 29.1) l.min-1 after respiratory training. In fact, six subjects ventilated more and cycled for a shorter time, whereas two subjects ventilated less and cycled for a longer time after the respiratory training than in the control CET. In general, the subjects cycled longer the lower the VE, if all three CET are compared. It is concluded that Raw measured immediately after exercise is independent of exercise-induced hyperventilation and hypocapnia and is probably not involved in limiting tcend, and that tcend at a given exercise intensity is shorter when VE is higher, no matter whether the higher VE occurs before or after respiratory training or after CO2 inhalation.

A possible pre-zollinger-ellison state: report on a novel lesion.

OBJECTIVE: To describe a patient with a potential harbinger of Zollinger-Ellison syndrome. METHODS: We present a case of a 29-year-old woman with persistent galactorrhea and gastric distress, who was a member of an extensive multiple endocrine neoplasia (MEN) I kindred. Both clinical and laboratory findings are reviewed. RESULTS: Laboratory studies were notable for persistent hypercalcemia and increased levels of parathyroid hormone and fasting pancreatic polypeptide. Because of nonspecific upper gastrointestinal distress, which was sometimes responsive to antacids, the patient underwent further diagnostic evaluation. Baseline gastrin levels were normal. A secretin challenge test yielded normal results. At upper endoscopy, visual findings in the stomach and duodenum were unremarkable. A raised nodule (4 by 2 by 2 mm) was removed from an otherwise normal-appearing duodenum as a routine biopsy procedure. The acinar architecture, the inconspicuous nucleoli, and the granular, eosinophilic cytoplasm of the cells were diagnostic of a neuroendocrine tumor. Histologic immunohistochemical staining was positive for gastrin but negative for pancreatic polypeptide. RNA studies were not technically possible. Subsequently, serum pancreatic polypeptide levels normalized. The patient ultimately had hyperplastic parathyroid glands resected. CONCLUSION: The duodenal lesion may be a very early gastrinoma, a preclinical manifestation of the Zollinger-Ellison syndrome. The role of early resection of such lesions remains to be determined.

Heterogeneous activity of pulmonary vagal receptors during high-frequency oscillation ventilation.

The purpose of the study was to examine the response of vagal pulmonary slowly adapting stretch receptors (SAR) to high-frequency oscillation ventilation (HFO) in rabbits by analyzing the afferent activity recorded in vagal single-fiber preparations. The vagal afferent activity was recorded during short runs of HFO with a stroke volume of 2-3 ml/kg applied at oscillation frequencies (fosc) of 5, 10, 15, 20, and 25 Hz and each frequency at three levels of mean airway pressure (P(aw)), namely, 1, 3, and 8 cm H2O. The receptor discharge rates during HFO were compared with those during quiet spontaneous breathing as well as during static lung inflations and deflations. The majority of SAR was stimulated by HFO, however, the SAR discharge patterns during HFO were less homogeneous than during static lung inflations. The heterogeneity of SAR responses to HFO became pronounced with increasing P(aw) and fosc. From the results, we conclude that HFO elicits heterogeneous discharge patterns of SAR, but the previously reported heterogeneity of responses of rapidly adapting receptors was even greater. This heterogeneity of vagal activity is probably the result of heterogeneous mechanical conditions within the lungs during HFO and may, in turn, give rise to the various types of respiratory reflex responses to HFO.

Running training and co-ordination between breathing and running rhythms during aerobic and anaerobic conditions in humans.

The study was carried out on ten triathletes, six sprinters and ten subjects not trained in running (controls) to assess the effects of training history on the co-ordination between breathing and running rhythms during running on a treadmill. Three exercise intensities were used: 50%, 80% and 110% of the subject's anaerobic threshold (AT). All three intensities were performed twice: once with spontaneous breathing and once with breathing intentionally co-ordinated to the running rhythm. Heart rate, respiratory parameters and leg movements were continuously recorded. Blood lactate concentrations were measured discontinuously. The degree of co-ordination between running and breathing was quantified as the percentage of inspirations and/or expirations starting during the same phase of step. The results showed that the degree of both spontaneous and intended co-ordination at aerobic exercise intensities was in all three groups the same and increased in all groups with increasing intensity from 50% to 80% of AT; further increase of intensity to 110% of AT was associated with a significant decrease of co-ordination in controls and sprinters, whereas triathletes were able to maintain the same high degree of co-ordination as at 80% of AT. It was concluded that running training of either type at aerobic work loads had no effect on the co-ordination between running and breathing rhythms. At anaerobic intensities, however, the degree of co-ordination between running and breathing rhythms was higher in the endurance trained athletes than in the sprinters or in the untrained subjects. The degree of co-ordination increased with increasing regularity of breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical respiratory system input impedance during high-frequency oscillatory ventilation in rabbits.

OBJECTIVES: To study the mechanical properties of the rabbit respiratory system during high-frequency oscillatory ventilation by means of mechanical respiratory impedance measurement and to characterize the changes in oscillation mechanics of the respiratory system occurring after bilateral vagotomy. DESIGN: Acute experimental trial. SETTING: Physiology laboratory. SUBJECTS: Ten adult rabbits (mean body weight 3.1 kg). MEASUREMENTS AND MAIN RESULTS: Anesthetized rabbits were exposed to short runs of high-frequency oscillatory ventilation, with stroke volumes of 5.0, 6.6, and 10.0 mL, applied at oscillation frequencies of 10, 15, 20, and 25 Hz before and after vagotomy. Mechanical respiratory input impedance was determined from the pressure and flow signals simultaneously measured at the airway opening and analyzed in terms of its real and imaginary parts. (The real part of respiratory impedance characterizes the resistive property of the lungs and chest wall; the imaginary part of respiratory impedance characterizes the elastic and inertial properties of the lungs and chest wall.) At all stroke volumes and oscillation frequencies studied, vagotomy resulted in a decrease in the real part of respiratory impedance. After vagotomy, the real part of respiratory impedance was stroke volume-independent, and exhibited negative frequency dependency. Vagotomy also led to a decrease in the imaginary part of respiratory impedance, mainly at lower oscillation frequencies, and thus, to a higher resonant frequency of the respiratory system. CONCLUSIONS: Mechanical respiratory impedance measurement proved to be a useful method to study the mechanical properties of the respiratory system during high-frequency oscillatory ventilation. The results suggest that vagally mediated reflex changes in respiratory system mechanics are associated with high-frequency oscillatory ventilation, depending on the ventilatory variables that are used.

The effects of acute altitude exposure in Swiss highlanders and lowlanders.

The functional characteristics at rest in responding to stepwise acute exposure to simulated altitude (6000 m) were compared in 10 acclimatized mountaineers (highlanders), residents of Zermatt (1616 m) working at an altitude up to about 4000 m, and in 11 nonacclimatized control subjects (lowlanders) living and working in Zurich (450 m). In comparison with the lowlanders, the highlanders showed at altitude significantly greater hyperventilation, lower heart rate and systolic blood pressure, smaller haemoconcentration, lower urodilatin secretion and natriuresis, and a preserved neuropsychological ability (attentiveness) and vasomotor tone (diastolic blood pressure); the critical altitude at which hypoxic short-term adaptation became insufficient was 6000 m. The lowlanders, however, manifested reduced tolerance of hypoxia, i.e. insufficient short-term adjustment with subjective and objective distress coinciding with the first signs of hypoxia of the central nervous system, already apparent at and above 4000 m. It was concluded that the functional differences between highlanders and lowlanders in responding to acute gradual hypoxia indicated factors contributing to altitude acclimatization.

Discharge of pulmonary rapidly adapting stretch receptors during HFO ventilation.

High-frequency oscillatory ventilation (HFOV) has been shown to stimulate slowly adapting pulmonary stretch receptors (PSR) and thereby to inhibit spontaneous breathing, i.e. HFOV prolongs expiration or even elicits normocapnic apnea. However, during HFOV respiratory effects possibly mediated by pulmonary rapidly adapting receptors (RAR) have also been observed, e.g., diaphragmatic activation or augmented breaths. Therefore, we analyzed HFOV-induced changes in RAR activity in anaesthetized rabbits by mean of single fibre preparations of vagal RAR afferents. HFOV was applied in several combinations of airway pressure (Paw) and oscillation frequency (fOsc). In the sample of 60 RAR fibres prepared in 20 rabbits we found a wide spectrum of discharge patterns during HFOV. The inspiratory discharge rate during HFOV was increased in 38, decreased in 10, and unchanged in 12 RAR. The expiratory discharge rate was increased in 34, decreased in 17, and unchanged in 9 RAR. The effects of gradually changing Paw or of fOsc during HFOV were different in different fibres. In 17 fibres both inspiratory and expiratory discharge rates rose with increasing Paw during HFOV, whereas 19 fibres were not affected by increasing Paw. In some fibres either the inspiratory (12) or the expiratory (9) activity was inhibited in proportion to increasing Paw. From these results we conclude, that (a) the changes of RAR activity during HFOV are heterogeneous and the reflex effects of RAR stimulation may be balanced by RAR with decreased activity; (b) this heterogeneity of RAR discharge patterns explains the dominancy in the control of breathing during HFOV of the homogeneously stimulated PSR; and (c) depending on HFOV ventilatory parameters used the overall RAR stimulation may be strong enough to overrule the inspiration-inhibiting effects of PSR.

Reflex apnea induced by high-frequency oscillatory ventilation in rabbits.

In rabbits with intact vagus nerves, HFOV applied for 10-20 s caused apnea (i.e., respiratory arrest for as long as HFOV lasted) accompanied by tonic discharges of the diaphragm. To identify the vagal mechanisms involved in this type of apnea, the vagus nerves of anaesthetized rabbits were gradually cooled from 37 degrees C to 0 degree C, i.e., the vagal fibres were, corresponding to their diameter, successively blocked. At each temperature, the effects of HFOV on spontaneous breathing were compared with those of static lung inflation and deflation: Between 20 degrees C and 14 degrees C, the lung inflation reflex (mediated by pulmonary slowly adapting stretch receptors = PSR) was weakened or abolished, whereas the lung deflation reflex (mediated by rapidly adapting stretch receptors = RAR) was reinforced; the HFOV-induced apnea occurred less frequently, however, the accompanying diaphragmatic activity was enhanced. Between 14 degrees C and 5 degrees C, both HFOV and large static inflation caused a slight increase of breathing frequency in the majority of animals. Some animals, however, responded even below 14 degrees C by apnea to both HFOV and inflation, and, under these conditions, both HFOV- and inflation-induced apnea were accompanied by a pronounced tonic diaphragmatic activity. At 5 degrees C, the effects of HFOV as well as of inflation (except in two animals) and deflation were abolished. From the results we conclude that in rabbits the apnea during HFOV is mainly mediated by stimulation of PSR, and the concomitant tonic activity of the diaphragm is mainly due to stimulation of RAR, as it is reinforced with gradual blockade of PSR fibres and abolished when only non-myelinated fibres are intact.

[Is altitude good for health?]. / Ist die Höhe gesund?

Health at altitude depends on the success of functional adjustments. Only the success of the short-term adjustments including increased tidal volume, acceleration of circulation, centralization of blood volume, hemoconcentration and adjustment of de diuresis to reduce cardiac volume overload render acclimatization possible. During these long-term adjustments, which always remain incomplete at altitudes above 2000 to 3000 m, mainly the cardiovascular economy and the respiratory efficiency are improved. Failure of the short-term adjustments excludes acclimatization and may be due to reduced physical capacity or to excessive physical activity (too fast too high). It is associated with sympathetic cardiac volume overload, central hypoxia, antidiuresis and distress which result in acute mountain sickness. Health at altitude may be preserved by moderating the ascent, the duration and the physical activity there.

Altitude diuresis: endocrine and renal responses to acute hypoxia of acclimatized and non-acclimatized subjects.

As a result of our recently published studies we have thought that altitude diuresis resulting from hypoxic stimulation of the arterial chemoreceptors reduces the cardiac volume overload. To test this hypothesis, cardiovascular, endocrine and renal responses to stepwise acute exposure to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers a mean of 24 days, SD 11, after descending from Himalayan altitudes of at least 4,000 m, with those found in ten non-acclimatized recumbent volunteers. The results showed that natriuresis and diuresis typified the renal responses to altitude exposure of both the acclimatized as well as non-acclimatized subjects, as long as altitude was well tolerated. It was concluded that the renal effects were mediated by atrial natriuretic peptide release and slight suppression of arginine-vasopressin (AVP) secretion, that the increased urine flow at altitude offset the cardiac (volume) overload resulting from hypoxic stimulation of the arterial chemoreceptors, and that enhanced AVP secretion, as found in the non-acclimatized subjects at and above 4,000 m, coincided with subjective and objective distress, i.e. with inadequate altitude adjustment owing to insufficient chemoreflex effects and central hypoxia.

Respiratory, circulatory and neuropsychological responses to acute hypoxia in acclimatized and non-acclimatized subjects.

Respiratory, circulatory and neuropsychological responses to stepwise, acute exposure at rest to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers 24 days, SD 11 after descending from Himalayan altitudes of at least 4,000 m with those found in ten non-acclimatized recumbent volunteers. The results showed that hypoxic hyperpnoea and O2 consumption at high altitudes were significantly lower in the mountaineers, their alveolar gases being, however, similar to those of the control group. In the acclimatized subjects the activation of the cardiovascular system was less marked, systolic blood pressure, pulse pressure, heart rate and thus (calculated) cardiac output being always lower than in the controls; diastolic blood pressure and peripheral vascular resistance, however, were maintained throughout in contrast to the vasomotor depression induced by central hypoxia which occurred in the non-acclimatized subjects at and above 4,000 m [alveolar partial pressure of O2 less than 55-50 mmHg (7.3-6.6 kPa)]. It was concluded that in the acclimatized subjects at high altitude arterial vasodilatation and neurobehavioural impairment, which in the non-acclimatized subjects reflect hypoxia of the central nervous system, were prevented; that acclimatization to high altitude resulted in a significant improvement of respiratory efficiency and cardiac economy, and that maintaining diastolic blood pressure (arterial resistance) at and above 4,000 m may represent a useful criterion for assessing hypoxia acclimatization.

Circadian rhythms of specific airway conductance and bronchial reactivity to histamine: the effects of parasympathetic blockade.

In ten healthy, nonsmoking, non-atopic, young volunteers, specific airway conductance and bronchial response to aerosolized histamine were measured plethysmographically at intervals of 4.8 h during two periods of 24 h, i.e. one day without, the other with, a parasympatholytic aerosol (0.20-0.24 mg ipratropium bromide) inhaled 1 h before each measurement, in order to determine the role of the parasympathetic innervation in the circadian rhythms of the airways. Specific airway conductance and bronchial reactivity showed clear circadian variations with corresponding peak times (16.11 and 04.41 h, respectively). Topical vagal blockade markedly increased specific conductance and resulted in a significant reduction of its rhythm amplitude, whereby the strong correlation between specific conductance and heart rate was significantly diminished. On the other hand, bronchial reactivity to histamine was lowered without flattening of its circadian rhythm. It is concluded that central parasympathetic outflow is an essential factor for the circadian rhythm of bronchial tone and, thus, for the increase in bronchial resistance at night.