Cardiac output,arterial and mixed-venous O2 saturation,and blood O2 dissociation curve in growing rats adapted to a simulated altitude of 3500 m

Summary In rats adapted to a simulated altitude of 3500 m cardiac output measured at hypoxia by the direct Fick principle was significantly lower than in the control animals (mean values 54.3 ml/min and 69.8 ml/min, resp.). The decrease of cardiac output was accompanied by an increase of arterio-venous O₂ difference and a decrease of stroke volume in the adapted rats. It is suggested that the decrease of cardiac output might be related to the increase of hematocrit. The adapted rats also showed higher arterial and mixed-venous O₂ content (both at hypoxia) and increased O₂ capacity. Arterial O₂ saturation of the animals previously exposed to simulated high altitude hypoxia was significantly higher (67.3% as against 61.2% in the controls). The standard O₂ dissociation curve showed lower oxygen affinity in the blood of the adapted animals but no physiological advantage concerning the transport of O₂ to the tissues was found. In another group of animals the Bohr factor was estimated and no difference was found between rat and human blood.     

Oxygen transport in guinea pigs native to high altitude (Junin,Peru, 4,105 m)

In guinea pigs native to high altitude in the Andes (Peru) the arterial and mixed-venousP _{O 2},P _{CO 2}, pH, and O₂ content were measured at high altitude during breathing ambient air.Identical measurements were done in Nijmegen, The Netherlands, on sea-level natives and on guinea pigs exposed for 4–5 weeks to simulated altitude in a low pressure chamber, while breathing ambient air (normoxia) or an hypoxic mixture of O₂ in N₂ with aP _{I O 2} similar to that of the ambient air at high altitude. A standard blood O₂ dissociation curve (ODC) was estimated in vitro (at pH=7.4 and 37.5°C), and a standard in vivo ODC was derived from measuredP _{O 2},S _{O 2} and pH in all three groups.Both guinea pigs native to natural or simulated high altitude had a higher hematocrit and blood O₂ capacity than sea-level controls. These increased altitude values were, however, almost the same as the sea-level values of man or rat. No difference in the ideal alveolararterialP _{O 2} difference or lung diffusing capacity for O₂ was found between (natural or simulated) high altitude animals and their corresponding controls, when measured at hypoxia. Mixed-venousP _{O 2} was higher in guinea pigs from the natural high altitude (but not in those from the low pressure chamber) when compared with control sea-level natives studied at hypoxia. No difference among groups in cardiac output was found, while breathing the same inspiratory mixture. In the guinea pigs native to high altitude a higher P₅₀ and a lower Hill numbern for the in vitro ODC were found when compared with the controls or with the guinea pigs exposed to simulated high altitude. This was not observed when the ODC's were estimated in vivo.The rather modest polycythemic response to high altitude in guinea pigs coincides with a low value of P₅₀, when related to body weight. In this respect the guinea pig seems to be more closely related to the typical high altitude mammals like Andean camelids and rodents than to man or rat that respond to high altitude with a pronounced polycythemia and possess a rather high P₅₀ with respect to body weight.All data obtained in Peru are part of the scientific material acquired during the Italian Lake Mountain Scientific Expedition to Peru, march and April 1978, under the direction of Prof. Dr. P. G. Data from the University of Chieti, Italy.Part of the results were presented at the 12. Atmungsphysiologische Arbeitstagung, Göttingen, FRG, January 26–27, 1979     

Hypoxic pulmonary steady-state diffusing capacity for CO and alveolar-arterial O2 pressure differences in growing rats after adaptation to a simulated altitude of 3500 m

Summary Steady-state pulmonary diffusing capacity for CO and alveolar-arterial O₂ pressure differences were measured at hypoxia in growing rats adapted to a simulated altitude of 3500 m. The pulmonary diffusing capacity was significantly higher and the alveolar-arterial gradients were significantly lower in the adapted animals as compared with the controls exposed to hypoxia for the first time. The increased diffusing capacity could be explained entirely by the increase of blood O₂ and CO capacity whereas the decrease of gradients might be explained by the increase of blood O₂ capacity together with an increase of the arterio-venous O₂ difference.     

Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve

Theoretical deductions have shown that a shift of the blood O₂ dissociation curve (ODC) to the right might improve O₂ transport to tissues at normoxia and at mild hypoxia whereas at severe hypoxia the organism should be better off with an ODC shifted to the left (Turek et al., 1973b; Turek and Kreuzer, 1976). The present study was performed in order to ascertain this ambiguous effect of an ODC shift depending on the degree of hypoxia in intact animals. A major displacement of the ODC to the left was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals received sodium chloride (NaCl) instead. Arterial and mixed-venous , , and pH were measured at normoxia and during breathing 14.9, 8.0, or 5.6% O₂ in N₂ in both groups. From , pH, ODC and arterial hematocrit, arterial and mixed-venous O₂ contents were estimated and as an index of blood O₂ extraction was obtained. At normoxia and during breathing 14.9% O₂ the NaOCN rats had a lower mixed-venous than the NaCl rats without any difference in pH. Arterio-venous O₂ difference did not differ at normoxia but was lower in NaOCN rats at 14.9% O₂. However, at 8.0 and 5.6% O₂ the NaOCN rats had a higher mixed-venous , an increased , and a higher pH (arterial and mixed-venous). At 5.6% O₂ the NaCl rats developed a severe acidosis concomitant with pronounced hypocapnia. These findings confirm that rats with a left-shifted ODC have an impaired O₂ transport to tissues at normoxia and mild hypoxia but a more efficient O₂ transport at severe hypoxia as compared with rats with an unshifted ODC, in agreement with our previous theoretical studies.Preliminary communications of part of this material at the FASEB Meeting in Anaheim, California, on April 11–16, 1976 (Fed. Proc.35, 526, 1976), and at the Dutch Federation Meeting in Amsterdam on April 21–23, 1976 (Volume of Abstracts, p. 381)     

Methodische Untersuchungen zur polarographischen Messung der Atmung und des „kritischen Sauerstoffdrucks” bei Mitochondrien und isolierten Zellen mit der membranbedeckten Platinelektrode

Summary In growing rats adapted to a simulated altitude of 3500 m for about 4 weeks and in their controls the evolution of cardiac ventricular weight was followed. The increase of total ventricular weight found in the adapted animals can be attributed exclusively to the increase of right ventricular weight. In other adapted and control animals cardiac capillary densities, muscle fiber diameter and external capillary radius were estimated and fiber—capillary ratio and diffusion distance were calculated. There was an increase of capillary density together with a decrease of muscle fiber density, fiber-capillary ratio and diffusion distance in the right but not in the left ventricle of the adapted rats. The muscle fiber diameters, however, were larger in both heart ventricles of the rats exposed to a simulated high altitude, especially in the right ventricle. This indicates that true hypertrophy of the muscle fibers is mainly responsible for the increase of right ventricular weight. In the left ventricle, however, a hypertrophy of the muscle fibers together with a decrease of stroma components is demonstrated. The physiological importance of the shorter diffusion distance in the right ventricle of the high altitude adapted rats is discussed and it is suggested that the shorter diffusion distance may help to keep the tissue O₂ partial pressure above the critical value, mainly also in extreme situations with high myocardial O₂ consumption.     

Myoglobin distribution in the heart of growing rats exposed to a simulated altitude of 3500 m in their youth or born in the low pressure chamber

Summary Reynafarje's (1963) spectrophotometric method was modified for the study of myoglobin concentration in rat hearts. The influence of age and body weight was evaluated and the age was found to be better correlated with myoglobin concentration than the weight. The influence of simulated altitude of 3500 m was studied in animals exposed to hypoxia at the age of about 34 days and in animals born in the low pressure chamber. In the first group a higher myoglobin concentration was found but only in the right ventricle, together with unilateral hypertrophy, as compared with control animals. In the group of animals born at simulated altitude a severe cardiomegaly developed which was most pronounced in the right ventricle. The myoglobin concentration in the hearts from this group was unchanged in the right ventricle and was lower in the left ventricle and septum.     

Standardized hemorrhagic shock in rats after acute and chronic exposure to high altitude

Acute exposure to high altitude for 1 day in rats caused an increase in hematocrit (Hct) with no change in mean arterial blood pressure (mABP) from the non-altitude control, whereas after prolonged exposure to altitude (5-6 weeks) there were increases in both Hct and mABP. No changes in total plasma protein (TPP) and plasma osmolality (POsm) from control rats were observed in all altitude-exposed animals. The ability of the acutely and chronically altitude and non-altitude exposed rats to resist hemorrhage was studied. Hemorrhage was standardized at mABP in the range of 30-35 mmHg. Chronic exposure to altitude increased the initial and maximum volume of blood withdrawn as well as the oligemic and survival times, whereas acute altitude exposure did not. The higher ability to resist standardized hemorrhagic shock of the chronically altitude exposed rats seemed to result, in part, from their greater hemodilution and better arterial blood pressure regulation. No difference in the rate of hemodilution as well as hemorrhagic tolerance was observed between the 1-day altitude and control rats. The difference in rate of hemodilution between the chronic altitude and control animals could not be due to arterial hyperosmolality since the magnitude of change in POsm during blood loss was the same for all animals groups.     

The effect of high oxygen tensions on the mechanical properties of rat lungs

1. The average mechanical properties of groups of lungs or lung—thorax systems from pathogen-free rats weighing approximately 200 g were determined. Static pressure—volume curves and resistances to air-flow were obtained.

2. Six series, each of sixteen rats, were studied. Eight experimental rats in each series were exposed to 4 atm O₂ (OHP) in a transparent pressure chamber; the other eight rats, which served as controls, were obtained from the breeder at the same time and studied at the same time.

3. In four series, the experimental animals were killed 10 min after gasping due to OHP had been definitely established. One series was a control in which experimental animals were exposed to 4 atm of pressure in an atmosphere containing oxygen at a tension of 150 mm Hg for 190 min. The experimental animals in the sixth series were exposed to 4 atm O₂ for 2 hr and none of them gasped.

4. Gross and histological examination of sixteen rats, eight of which were killed after 10 min of gasping at 4 atm O₂, showed that at this stage of intoxication there was no evidence of pulmonary pathology.

5. In none of the series studied were the static pressure—volume curves for deflation shifted, i.e. OHP did not affect the elastic properties of the lungs or the alveolar surfactant.

6. In two series studied 10 min after gasping behaviour had been established there was a significant decrease of resistance to air-flow and a shift to the left of the static pressure—volume curve for inflation with air. The rats in both these series were sedated with pentobarbitone and then killed with pentobarbitone injected into the jugular vein.

7. The decrease in resistance to air-flow was interpreted as broncho-dilatation and a possible mechanism whereby OHP produces broncho-dilatation is discussed.

     

Befunde am Glomus caroticum der Ratte nach Aufenthalt in einer simulierten Höhe von 7500 m

Zusammenfassung Weibliche Wistar-Ratten wurden über einen Zeitraum von 99 Tagen stufenweise in einer speziell konstruierten Unterdruckkammer an eine simulierte Höhe von 7500 m adaptiert. Gegenüber Kontrolltieren sind das Größenwachstum und die Gewichtszunahme vermindert. Erythrocytenzahl, Hämoglobin und Hämatokrit sind vermehrt, die Leukocytenzahl erniedrigt. Das Herz zeigt eine starke, vorwiegend rechtsseitige muskuläre Wandhypertrophie. Die Carotiskörperchen der adaptierten Tiere wurden histometrisch untersucht und mit denen der Kontrollen verglichen. Es fand sich eine sechsfache Vergrößerung der Glomera der Versuchstiere, die zum überwiegenden Teil auf eine erhebliche Capillardilatation zurückzuführen ist. Das Zellvolumen der Glomera ist um das Vierfache vermehrt. Die Hauptzellen (Typ I-Zellen) sind groß, das Cytoplasma hell und vacuolisiert. Dies läßt auf eine Degranulation unter dem Einfluß der erniedrigten O₂-Spannung bei barometrisch erniedrigtem Luftdruck schließen. Innerhalb der Glomera kommt es zu capillären Thrombosen und großen Vernarbungen.

---

Observations in the glomus caroticum of rats maintained at a simulated altitude of 7500 m

Summary Over a period of 99 days female Wistar rats were gradually adapted to a simulated altitude of 7500 m in a low-pressure chamber. Compared to controls the animals showed smaller increases in weight and size. The number of erythrocytes, the haemoglobin concentration and the haematocrit were raised and the leukocyte count decreased. The heart showed a considerable, predominantly right-sided hypertrophy. The carotid bodies of the adapted animals were examined histometrically and compared with those of the controls. In the experimental animals we found a six-fold increase in the size of the glomera, which was due mainly to capillary dilatation. The volume of the cells was four times greater. The chief cell (type-I-cells) were large, the cytoplasm pale and vacuolized, indicating degranulation under the influence of a lowered pO₂ combined with decreased atmospheric pressure. Within the glomera there were capillary thromboses and scarring.

     

Hemodynamic and ventilatory response to different levels of hypoxia and hypercapnia in carotid body-denervated rats

OBJECTIVE:

Chemoreceptors play an important role in the autonomic modulation of circulatory and ventilatory responses to changes in arterial O₂ and/or CO₂. However, studies evaluating hemodynamic responses to hypoxia and hypercapnia in rats have shown inconsistent results. Our aim was to evaluate hemodynamic and respiratory responses to different levels of hypoxia and hypercapnia in conscious intact or carotid body-denervated rats.

METHODS:

Male Wistar rats were submitted to bilateral ligature of carotid body arteries (or sham-operation) and received catheters into the left femoral artery and vein. After two days, each animal was placed into a plethysmographic chamber and, after baseline measurements of respiratory parameters and arterial pressure, each animal was subjected to three levels of hypoxia (15, 10 and 6% O₂) and hypercapnia (10% CO₂).

RESULTS:

The results indicated that 15% O₂ decreased the mean arterial pressure and increased the heart rate (HR) in both intact (n = 8) and carotid body-denervated (n = 7) rats. In contrast, 10% O₂ did not change the mean arterial pressure but still increased the HR in intact rats, and it decreased the mean arterial pressure and increased the heart rate in carotid body-denervated rats. Furthermore, 6% O₂ increased the mean arterial pressure and decreased the HR in intact rats, but it decreased the mean arterial pressure and did not change the HR in carotid body-denervated rats. The 3 levels of hypoxia increased pulmonary ventilation in both groups, with attenuated responses in carotid body-denervated rats. Hypercapnia with 10% CO₂ increased the mean arterial pressure and decreased HR similarly in both groups. Hypercapnia also increased pulmonary ventilation in both groups to the same extent.

CONCLUSION:

This study demonstrates that the hemodynamic and ventilatory responses varied according to the level of hypoxia. Nevertheless, the hemodynamic and ventilatory responses to hypercapnia did not depend on the activation of the peripheral carotid chemoreceptors.     

缺氧性肺动脉和体动脉增压反应的研究——慢性间断缺氧的影响及其机制

雄性长白种(Landrace strain)幼猪10只,每天在低压舱内于4,000m模拟高原停留8小时,共30天。第31天再次缺氧时,其缺氧性肺动脉增压反应比急性缺氧组(11只)显著增强,但同时测得的全血量,血浆量和心输出量都无显著增加。仅血球量和红细胞压积增高,不过,都未达到足以影响肺动脉压的程度。股动脉血和肺动脉血的组织胺含量不仅未增加,反而下降。两组动物的肺血管阻力都增大,但前者更显著。两组动物的体动脉压在缺氧时都升高。在4,000m模拟高原,异搏停(钙离子拮抗剂)可致两组动物的肺动脉压和体动脉压明显下降,其作用可维持2小时以上。间接说明钙离子与缺氧性肺动脉和体动脉增压反应有关。     

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

Summary 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 < 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.Dedicated to Prof. A. Schreiber on the occasion of his 60th birthday     

Myocardial capillaries in guinea pigs native to high altitude (Junin,Peru, 4,105 m)

Quantitative evaluation of the myocardial left ventricular capillarity was performed in three groups of guinea pigs: a) animals native to high altitude collected in Andean mountains, b) animals born at sea level and subjected to a simulated high altitude postnatally, c) animals born and kept at sea level. The number of capillaries and muscle fibers/mm² as well as the fiber capillary ratio and the diffusion distance were similar in all three experimental groups. The only difference found during the detailed analysis of the myocardial capillarity was a slightly lower percentage of the myocardial tissue in the extreme distance from the capillary found in the hearts of high altitude natives when compared to sea level animals. From these morphometric data the distribution of diffusion distances was derived which can be approximated by lognormal distribution. Capillary inhomogeneity expressed as log standard deviation was found to be similar in all three groups.     

Arterial blood gases,muscle fiber diameter and intercapillary distance in cardiac hypertrophy of rats with an old myocardial infarction

In rats with a myocardial infarction due to ligation of the left coronary artery a marked right ventricular hypertrophy developed after 41/2 weeks. At this time no difference against control animals was observed in arterial , , pH, ideal alveolar , and alveolar-arterial O₂ pressure difference, as measured in unanesthetized animals at normoxia. In histological sections of the heart stained by PAS reaction capillaries and muscle fibers were counted, and the mean intercapillary distance and muscle fiber diameter were estimated. In the right ventricle of the rats with myocardial infarction both increased when compared with control animals or with sham-operated rats. Fibercapillary ratio was the same in all three groups. Similar results were obtained in the remaining undamaged tissue of the left ventricle of rats with a myocardial infarction when compared with the left ventricle of control or sham-operated rats. Findings concerning intercapillary distance suggest that also in the myocardium which remains intact during the development of the infarction and later hypertrophies, tissue oxygen transport might be impaired, particularly during a stress situation. Results in the right ventricle of rats with myocardial infarction show an opposite trend against rats exposed chronically to simulated high altitude, where in the hypertrophied right ventricle a shorter intercapillary distance occurs and therefore an improvement of tissue oxygen transport might be expected.Dedicated to Professor Dr. Adolf Faller, University of Fribourg, Switzerland, on his 65th birthdayPresented in part at the IXth World Conference of the European Society for Microcirculation, Antwerp, July 5–9, 1976     

Oxygen transport during early altitude acclimatization: A perspective study

Key aspects of the oxygen transport system were studied under supine, near-basal conditions in 6 male subjects, initially at low altitude (200 m) and subsequently over a 15-day sojourn on Pikes Peak (4300 m). Certain functions, including cardiac output, heart rate, mean arterial pressure and left ventricular work, were transiently increased with maximum values observed on day 2 of altitude exposure. Others, including arterial PO₂, O₂ saturation, and O₂ content passed through minimal values on the same day and then recovered somewhat as the sojourn progressed. Tidal volume and arterial pH exhibited relatively linear increases over the two-week sojourn while pulmonary minute volume and hemoglobin exhibited progressive increases which were especially pronounced during the first 5 days of exposure. Plasma volume, stroke volume, arterial PCO₂, and plasma HCO ₃ ^– concentration decreased progressively, with the more pronounced effects being observed during the first 5 days of exposure. A decrease in stroke volume and cardiac output on day 14 led to diminished arterial O₂ delivery. On the basis of the results and complementary data reported by others, it was concluded that altitude acclimatization progresses through three distinct but overlapping stages. Arbitrarily, the states were termed accommodation, acute acclimatization, and chronic acclimatization.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense     

Adaptive changes in cardiac myosin heavy chain and creatine kinase isozymic profiles in rats native of altitude

AIM: The developmental changes in the myosin heavy chain (MHC) profile, creatine kinase (CK) and lactate dehydrogenase (LDH) activities and isozyme expression occurring in heart were examined in rats born and living at altitude (La Paz, Bolivia, 3700 m, H(LP)) for 16 generations. We hypothesized that H(LP) rats respond differently to hypoxia than rats born and living at sea level, and secondarily exposed to altitude during 3 weeks (H(3W)). METHODS: The cardiac expression of MHC, CK and LDH was studied in left (LV) and right ventricle (RV) of H(LP) animals 1, 2, 3, 4 and 18 weeks after birth, and compared with control normoxic (C groups) and H(3W) animals. RESULTS: Rats secondarily exposed to hypoxia showed a lower alpha-MHC content than C or H(LP) rats in both LV and RV, 3 weeks after birth (P < 0.05), consistent with a delay in the maturation of the heart contractile phenotype. A global increase in the total CK activity was observed in the LV of H(3W) animals in comparison with C rats (P < 0.05), while no change was reported in H(LP) animals. In both ventricles, M-LDH activity was higher in H(3W) than in H(LP) and C rats (P < 0.05). The relative amount of alpha-MHC decreased by 20% in RV of 18-week-old H(LP) and H(3W) rats in comparison with C animals, consistent with the hypoxia-induced ventricular enlargement (P < 0.01). An increased activity of the foetal B-CK subunit was observed in both LV and RV of H(3W) rats in comparison with H(LP) and C animals (P < 0.05). CONCLUSION: This study demonstrates that rats native and living at altitude for several generations present some features relevant to genetic selection to altitude.     

Individual resistance of the organism and nerve cell to hypoxia

The correlation between the pattern of a neuron's reaction to acute hypoxia and individual resistance to oxygen deficit is studied on ratsin vivo as well as on surviving slices of their cerebellumin vitro. According to the survival time in a pressure chamber simulating an altitude of 11 km all the rats were divided into groups of high resistance, medium resistance, and low resistance to hypoxia. Survival time was 4.2 times longer in the high resistance group than in the low resistance group. In the cerebellar slices of high resistance animals 61.5% high-resistance neurons and 38.5% low-resistance neurons were recorded. On the other hand, in the high resistance animals the percentage of high-resistance neurons and low-resistance neurons was 31.2 and 68.8, respectively. The period of hypoxia development was 4.32 times longer in the high-resistance neurons as compared to low-resistance neurons. It is speculated that individual differences in the resistance to O₂ deficit are of a hereditary nature and manifest themselves not only on the level of the whole organism, but also in the individual nerve cell. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 454–457, November, 1994     

Avian embryos in hypoxic environments

Avian embryos at high altitude do not benefit of the maternal protection against hypoxia as in mammals. Nevertheless, avian embryos are known to hatch successfully at altitudes between 4000 and 6500 m. This review considers some of the processes that bring about the outstanding modifications in the pressure differences between the environment and mitochondria of avian embryos in hypoxic environments. Among species, some maintain normal levels of oxygen consumption ( ) have a high oxygen carrying capacity, lower the air cell-arterial pressure difference (P_AO2−P_aO2) with a constant pH. Other species decrease , increase only slightly the oxygen carrying capacity, have a higher P_AO2−P_aO2 difference than sea-level embryos and lower the P_CO2 and pH. High altitude embryos, and those exposed to hypoxia have an accelerated decline of erythrocyte ATP levels during development and an earlier stimulation of 2,3-BPG synthesis. A higher Bohr effect may ensure high tissue P_O2 in the presence of the high-affinity hemoglobin. Independently of the strategy used, they serve together to promote suitable rates of development and successful hatching of high altitude birds in hypoxic environments.     

Influence of changes in cardiac output on the acid-base status of arterial and mixed venous blood

While maintaining the arterial CO₂ tension constant near the normal level of the dog (4.3 kPa), we studied the influence of decreasing cardiac output on both the arterial and mixed-venous blood acid-base status in anaesthetized, artificially ventilated dogs. Cardiac output was manipulated by applying positive end-expiratory pressure (PEEP), and by -adrenergic blockade to suppress a compensatory heart rate response. The systemic vascular response was attenuated by -adrenergic blockade. Metabolic rate remained virtually unchanged when cardiac output decreased. Under these conditions a fall in cardiac output led to a shift of the arterial acid-base status in the direction of a metabolic acidosis. The changes occurring in the mixed-venous blood resembled those of an in-vivo CO₂ bufferline, with the shift being such as if a respiratory acidosis was developing.     

Respiratory function and blood gas variables in cystic fibrosis patients during reduced environmental pressure

Patients with cystic fibrosis (CF) suffer from hypoxaemia even under normobaric conditions and the reduction of inspiratory PO₂ (O₂ partial pressure) during air travel corresponding to an altitude of 1,800–2,450 m might be a problem for these patients. Ten CF patients and 27 healthy control subjects were investigated in a chamber where the ambient pressure was reduced to that found at 2,000 and 3,000 m. The respiratory function was reduced in the CF patients with a vital capacity of 3.1 (0.3) l [vs 4.9 (0.2) l in controls; mean (SEM)] and a forced expiratory 1-s volume of 2.1 (0.3) l [vs 4.3 (0.20 l in controls], unrelated to the reduction in ambient pressure. Mean arterial PO₂ decreased from 75 (4) mmHg [85 (1) mmHg in controls, P<0.01] at sea level to 58 (3) mmHg at 580 mmHg and to 46 (1) mmHg [58 (1) mmHg and 49 (2) mmHg in controls, n.s.] at 513 mmHg ambient pressure. These results indicate that during air travel with a cabin pressure that corresponds to an altitude of 2,500 m, the arterial PO₂ of CF patients is likely to remain above the accepted critical value of 50 mmHg. However, a further reduction of the pressure to that found at 3,000 m altitude may lead to severe hypoxia in patients with moderate airway obstruction.