An animal model of the relationship between systemic hypertension and repetitive episodic hypoxia as seen in sleep apnoea

SUMMARY  Multiple factors may be responsible for acute and chronic blood pressure changes during obstructive sleep apnoea. A popular hypothesis is that recurrent episodic hypoxia stimulates chemoreceptors which, in turn, cause sympathetically mediated vasoconstriction and perhaps long-term vascular remodelling. Disruption of sleep architecture secondary to frequent arousals may also cause chronic stress which may contribute to diurnal hypertension. A less likely factor elevating blood pressure is the effect of abrupt intra-thoracic pressure changes on venous return and cardiac output. The rat responds to chronic, recurrent episodic hypocapnic hypoxia (12-s bursts of nitrogen followed by air into Plexiglas chambers, every 30 s, 7h d^-1, 2–4% nadir ambient oxygen) with sustained increase in diurnal blood pressure (10–14 mmHg). Subsequent studies reveal that carotid sinus nerve section (chemodener-vation) and chemically induced peripheral sympathetic denervation with the neurotoxin 6-OH dopamine both eliminate this blood pressure-elevating effect of chronic episodic hypoxaemia. Using this model, Sprague-Dawley rats have been challenged with both eucapnic hypoxia and asphyxia and failed to show an additional blood pressure elevation above that caused by hypoxia (hypocapnic) alone. It appears that hypocapnic hypoxia creates a maximal stimulus to the sympathetic nervous system to which the addition of hypercarbia does not increase the blood pressure response. An alternative explanation is that the rat has protective mechanisms that limit the diurnal blood pressure response from further increase.     

Human erythropoietin response to hypocapnic hypoxia,normocapnic hypoxia,and hypocapnic normoxia

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO₂ to the hypoxic gas. On separate days, eight healthy male subjects were exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVAP = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other experiments were corrected for these spontaneous variations in each individual. At 2 h after ending hypocapnic hypoxia (10% O₂ in nitrogen), mean serum-EPO increased by 28% [baseline 8.00 (SEM 0.84) U · 1⁻¹, post-hypoxia 10.24 (SEM 0.95) U · 1⁻¹, P = 0.005]. Normocapnic hypoxia was produced by the addition of CO₂ (10% Co₂ with 10% O₂) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVAP > 0.05). Hypocapnic normoxia, produced by hyperventilation of room air, elicited a normoxic increase in the haemoglobin oxygen affinity without changing serum-EPO. Among the measured blood gas and acid-base parameters, only the partial pressures of oxygen in arterial blood during hypocapnic hypoxia were related to the peak values of serum-EPO (r = −0.81,P = 0.01). The present human EPO responses to hypoxia were lower than those which have previously been reported in rodents and humans. In contrast with the earlier rodent studies, it was found that human EPO production could not be triggered by short-term increases in pH and haemoglobin oxygen affinity per se, and the human EPO response to hypoxia could be suppressed by concomitant normocapnia without acidosis.     

Avian cerebral blood flow: influence of the Bohr effect on oxygen supply.

To clarify the problems of altitude tolerance in birds, we studied the combined effect of hypocapnia and hypoxia on cerebral blood flow (CBF) in ducks. CBF was measured by the xenon clearance method. Normocapnic hypoxia causes CBF to increase when the arterial O2 tension (PaO2) falls below 60--70 mmHg. Hypocapnic hypoxia significantly shifts the blood flow curve so that blood flow does not increase until a lower PaO2 (50--60 mmHg) is reached. This gives the appearance that hypocapnia suppresses the hypoxia-induced increase in CBF. However, due to the Bohr effect, the hypocapnic blood contains significantly more O2 than does the normocapnic blood at the same PaO2. Therefore, when CBF is expressed as a function of O2 content, rather than PO2, CBF in the hypocapnic group does not differ significantly from the CBF in the normocapnic group. We interpret this to mean that because of the significantly greater oxygen content of the hypocapnic blood at a given PaO2, the degree of hypoxia experienced by these brains is not as severe as that experienced by the normocapnic brains.     

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     

Exercise capacity in young adults with hypertension and systolic blood pressure difference between right arm and leg after repair of coarctation of the aorta

Coarctation of the aorta represents 5–7% of congenital heart defects. Symptoms and prognosis depend on the degree of stenosis, age at surgery, surgical method and the presence of other heart defects. Postoperative complications are hypertension, restenosis and an abnormal blood pressure response during exercise. This study includes 41 patients, 15–40 years old, operated in the period 1975–1996. All were exercised on a treadmill until maximal oxygen consumption was achieved. Blood pressure was measured in the right arm and leg before and immediately after exercise, and in the right arm during exercise. Oxygen consumption was monitored and we defined an aerobic phase, an isocapnic buffering phase and a hypocapnic hyperventilation phase. The resting systolic blood pressure correlates with the resting systolic blood pressure difference between right arm and leg. A resting systolic blood pressure difference between the right arm and leg of 0.13 kPa (1 mmHg) to 2.67 kPa (20 mmHg) corresponds with a slight increase in resting systolic blood pressure. This rise in blood pressure increases the aerobic phase of the exercise test, helping the patients to achieve higher maximal oxygen consumption. A resting systolic blood pressure difference of more than 2.67 kPa (20 mmHg) corresponds with severe hypertension and causes reduction in the aerobic phase and maximal oxygen consumption. Resting systolic blood pressure and resting systolic blood pressure difference between the right arm and leg are not indicators for blood pressure response during exercise. Exercise testing is important to reveal exercise-induced hypertension and to monitor changes in transition from aerobic to anaerobic exercise and limitation to exercise capacity.     

Hypophagia-induced hypometabolism during experimental anaemia in rats

Several investigators have reported a drop in oxygen (O₂) consumption (VO₂) and body temperature in laboratory animals during normobaric or hypobaric hypoxia. Hypophagia, with normal efficiency of protein utilisation for growth, was also observed. It has recently also been observed that hypometabolism is present during anaemic hypoxia. The present study was designed to test the experimental hypothesis that anaemic hypoxia induces hypometabolism secondary to hypophagia. Episodes of anaemia were created in adult male rats by either blood withdrawal through cardiac puncture (haemorrhagic anaemia) or phenylhydrazine administration (haemolytic anaemia). Haematrocrit, VO₂, and food consumption, as indirect estimations of the level of anaemia, energy production, and appetite, respectively, were serially measured in all animals during 7 days (acute experiments) or 17 days (chronic experiments). Positive correlations were found between the three parameters during development of and recovery from anaemia during each anaemic episode. When the amount of food offered to non-anaemic rats was equalised to that freely eaten by anaemic rats, VO₂ dropped in the former to almost the level found in the latter. Body composition changed during chronic anaemia because of a decrease in the lipid fraction of the body. The results confirmed the working hypothesis that hypometabolism, which has been considered as an immediate, emergency-type response to both hypoxic and anaemic hypoxia, can be considered as a response secondary to hypophagia because of depressed appetite. How appetite is adapted to the mechanisms which control O₂ convection and O₂ availability is not known at present.     

The effect of lower body positive pressure on the cardiovascular response to exercise in sedentary and endurance-trained persons with paraplegia

Exercise intolerance in persons with paraplegia (PARAS) is thought to be secondary to insufficient venous return and a subnormal cardiac output at a given oxygen uptake. However, these issues have not been resolved fully. This study utilized lower-body positive pressure (LBPP) as an intervention during arm crank exercise in PARAS in order to examine this issue. Endurance-trained (TP, n= 7) and untrained PARAS (UP, n= 10) with complete lesions between T6 and T12, and a control group consisting of sedentary able-bodied subjects (SAB, n= 10) were tested. UP and TP subjects demonstrated a diminished cardiac output (via CO₂ rebreathing) during exercise compared to SAB subjects. Peak oxygen uptake (V˙O_2peak) remained unchanged for all groups following LBPP. LBPP resulted in a significant decrease in heart rate (HR) in UP and TP (P≤0.05), but not SAB subjects. LBPP produced an insignificant increase in cardiac output (Q˙) and stroke volume (SV). The significant decrease in HR in both PARA groups may indicate a modest hemodynamic benefit of LBPP at higher work rates where circulatory sufficiency may be most compromised. We conclude that PARAS possess a diminished cardiac output during exercise compared to the able-bodied, and LBPP fails to ameliorate significantly their exercise response irrespective of the conditioning level. These results support previous observations of a lower cardiac output during exercise in PARAS, but indicate that lower-limb blood pooling may not be a primary limitation to arm exercise in paraplegia.     

Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia-induced pulmonary vasoconstriction in a porcine model

Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia‐induced pulmonary vasoconstriction. Methods: Fourteen anaesthetized, ventilated pigs, with a mean ± SEM weight of 30.5 ± 0.6 kg, were studied, in normoxia (FiO₂ 0.21) and with tezosentan (5 mg kg^?1) infusion during (n = 7) or before (n = 7) hypoxia (FiO₂ 0.10). Results: Compared to normoxia, hypoxia increased (P < 0.05) pulmonary vascular resistance (PVR) by 3.4 ± 0.7 WU, mean pulmonary artery pressure by 13.7 ± 1.3 mmHg, mean right atrial pressure by 1.9 ± 0.4 mmHg and decreased (P < 0.02) systemic vascular resistance (SVR) by 5.2 ± 2.1 WU. Pulmonary capillary wedge pressure (PCWP), mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood‐O₂‐consumption were unaltered (P = ns). Tezosentan infused during hypoxia, normalized PVR, decreased (P < 0.05) maximally mean pulmonary artery pressure by 7.5 ± 0.8 mmHg, SVR by 5.8 ± 0.7 WU, mean aortic blood pressure by 10.8 ± 3.0 mmHg and increased (P < 0.04) stroke volume by 8.5 ± 1.8 mL. Mean right atrial pressure, PCWP, heart rate, cardiac output and blood‐O₂‐consumption were unaltered (P = ns). Tezosentan infused before hypoxia additionally attenuated approx. 70% of the initial mean pulmonary artery pressure increase and abolished the PVR increase, without additionally affecting the other parameters. Conclusion: Dual endothelin receptor blockade during hypoxia attenuates the ‘sustained’ acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by approx. 62% and by normalizing PVR. Pre‐treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia‐induced mean pulmonary artery pressure rise by approx. 70% and abolishes the PVR increase, during stable circulatory conditions, without affecting oxygenation.     

Circulatory,respiratory and metabolic responses in Thoroughbred horses during the first 400 meters of exercise

Summary These studies investigated circulatory, respiratory and metabolic responses in four Thoroughbred geldings during the first 400 metres of galloping (mean speed 14.4±0.38 m · s^–1), cantering (mean speed 10.0±0.61 m · s^–1) and walking (mean speed 1.58±0.05 m · s^–1) from a standing start. A radio-controlled device which collected blood samples anaerobically during each 100 m section of the exercise track allowed analyses of changes in and functional relationships of the variables measured. During the 400 m gallop, the mean heart rate (HR) increased from 125 to 201 beats · min^–1 and the haematocrit (Hct) from 0.513 to 0.589 l/l^–1. The haemoglobin [Hb], lactate [LA] and potassium [K⁺] concentrations increased significantly, while the pH and the partial pressure of oxygen (PaO₂) decreased significantly. The arterial partial pressure of carbon dioxide (PaCO₂) and the plasma bicarbonate concentration did not change significantly. There were significant correlations between HR and Hct, HR and [Hb], HR and PaO₂, HR and pH, HR and PvCO₂, HR and [LA], HR and [K⁺], pH and [K⁺], Hct and PaO₂, [Hb] and PaO₂, PaCO₂ and PaO₂, [LA] and PaO₂, pH and PaO₂, [K⁺] and PaO₂, stride frequency and PaO₂. With the exception of the PvCO₂ which increased significantly, changes in venous blood during the gallop were in the same direction as those of arterial blood. Thirty seconds before the start of the gallop, both HR and [Hb] were significantly higher than at rest, providing an approximate three-fold increase in oxygen delivery compared to that of the resting state. During the canter neither PaO₂ nor PaCO₂ changed significantly, whilst HR, [LA] and [K⁺] increased significantly. Changes in other variables were in the same direction as during the gallop but to a non-significant extent. During the walk the PaO₂ increased significantly. We concluded that exercise-induced hypoxaemia developed within <20 s of the start of a gallop at 14 to 15 m · s^–1 and that its development was significantly related to changes in cardiac, respiratory, acidbase and metabolic components of the physiological response to heavy exercise. A preliminary canter followed by a ten minute walk before a gallop ensured that horses began galloping with a greatly enhanced systemic oxygen delivery.     

Oscillations in stroke volume and cardiac output arising from oscillatory ventilation in humans

Oscillations in the cardiovascular system have been observed in patients with periodic breathing. It is not clear whether these are driven by primary oscillations in the respiratory system or whether an intrinsic cardiovascular instability is required, as previous studies with subjects performing voluntary periodic breathing have failed to produce the cardiovascular oscillations. We investigated whether cardiovascular oscillations occurred in healthy controls performing voluntary periodic breathing. Six healthy subjects performed voluntary periodic breathing with guidance from a real-time computer display. We measured ventilation, end-tidal partial pressures of O2 (PO2) and CO2 (PCO2), heart rate, blood pressure (BP), arterial oxygen saturation and stroke volume and cardiac output by transthoracic impedance cardiography. Fourier analysis was used to quantify the size and phase of the periodic breathing-induced oscillations in these parameters. Periodic breathing (amplitude 30% of mean ventilation) induced oscillations in end-tidal PO2 (amplitude 0.8 kPa), end-tidal PCO2 (amplitude 0.3 kPa), R-R interval (amplitude 32.6 ms), systolic BP (amplitude 3 mmHg), diastolic BP (amplitude 3 mmHg), stroke volume (amplitude 8.0 ml, mean 79.5 ml) and cardiac output (amplitude 0.6 1, mean 5.9 l x min(-1)). The oscillations in stroke volume and cardiac output were nearly in phase with ventilation, with their peaks occurring 5.6 and 6.1 s, respectively, after the peak in ventilation. An oscillatory ventilatory pattern entrains the cardiovascular system in healthy controls into fluctuations, not only in heart rate and BP, but also in stroke volume and cardiac output.     

Cardiovascular effects in adolescents while they are playing video games: A potential health risk factor?

We analyzed heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), oxygen consumption, and carbon dioxide production in 17 male adolescents during a racing simulation video game (VG) and compared to resting state (RS) and exercise testing (ET) measures. We were able to demonstrate a significant (p<.005) increase from RS to VG concerning HR (+13.1 bpm), SBP (+20.8 mmHg), and DBP (+12.1 mmHg) with SBP and DBP elevations exceeding 2 SD in all children and 14/17 children, respectively. The energy consumption during VG (max 1.71 kcal/min) was unaltered compared to RS and significantly lower compared to ET even at the starting strain of 25 W (1.94 kcal/min). Hemodynamic parameters tested demonstrated lower HR, unchanged SBP, and higher DBP during the VG compared with ET. Comparing all measured parameters it can be said that the relation of blood pressure and energy consumption during VG might not be favorable.     

Heart rate response to breath-holding during supramaximal exercise

Summary The cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO₂ and PCO₂ were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O₂ for 1 min before apnoea (O₂-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O₂-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O₂-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure.     

Cardiovascular and respiratory responses to passive leg cycle exercise in people with spinal cord injuries

The purpose of this study was to determine the effect of passive leg cycle exercise (PLE) on cardiovascular and respiratory responses in people with spinal cord injuries (PSCI). Eight PSCI with lesions from T8 to L1 and five control subjects (CS) performed PLE at pedalling frequencies of 20 or 40 rpm for 7 min at room temperature of about 25°C. We measured, at rest and during PLE, the pulmonary ventilation (V_E), oxygen uptake (VO₂), cardiac output (Q), stroke volume (SV), heart rate (HR) and arterial blood pressure, as well as the skin blood flow (SBF) in the lower limb after PLE. An increase in pedalling frequency promoted an increase in V_E and VO₂ in both groups. Compared with the CS, the PSCI showed significantly smaller increases in VO₂ (P < 0.05). The Q_c was significantly elevated during PLE at 20 and 40 rpm in CS, and at 40 rpm in PSCI (P < 0.05). In CS, it resulted from increases in both SV and HR, whereas in PSCI, it was contributed to by a greater increase in SV without a rise in HR. In CS, the increase in pedalling frequency promoted the increases in SV and HR and consequently in Q_c In PSCI, however, the values remained constant irrespective of pedalling frequency. The arterial blood pressure and SBF in the lower limbs were unchanged by PLE in both groups. These results would suggest that passive leg exercise promotes venous return from the paralyzed lower limbs in PSCI.     

Effect of airway anaesthesia on the ventilatory and heart rate responses to isocapnic progressive hypoxia

The effect of airway anaesthesia by lidocaine inhalation on the hypoxic ventilatory response was examined together with the heart rate response by the isocapnic progressive hypoxia test in human subjects. During the test, end-tidal PCO2 (PETCO2) was maintained at the resting level. However, because resting PETCO2 tends to decrease by airway anaesthesia, we conducted the test at the resting PETCO2 determined both before (normocapnic) and after lidocaine (hypocapnic). Ventilatory and heart rate response were evaluated as a linear function of oxygen saturation of the arterial blood (SaO2). In the "hypocapnic" runs, ventilatory responses tended to be depressed, while the slope of heart rate response-PETCO2 relationship increased after lidocaine. However, when PETCO2 was restored to the normocapnic level, ventilation apparently increased from the control, and the augmented slope in the heart rate response disappeared. Although the elevated ventilation in normocapnic hypoxia might be due simply to the increased ventilatory response to CO2, we suggested that the augmented slope in the heart rate response in hypocapnic hypoxia might be related not only to PETCO2 level itself but also to the direct effect of airway anaesthesia.     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.     

Cardiovascular response to exercise in humans following acclimatization to extreme altitude

The purpose of this study was to assess the effects of acclimatization to extreme altitude on the cardiovascular system, using vagal and adrenergic blockade and acute restoration of normoxia during exercise to maximum with one and two legs. Fourteen climbers on an expedition to the Himalayas were studied at a lower base camp (5250 m) following 56–81 days at altitudes between 5250 and 8700 m. After acclimatization, peak heart rate (HR_peak), oxygen uptake (o_2k) and noradrenaline (NA) were similar during maximal one- and two-legged cycling, whereas peak plasma lactate was higher during the one-legged protocol. HR_peak (range 113–168 beats min“¹) was lowest when subjects returned from the higher camps. The degree of partial restoration of HR_peak to more normal values within seconds of 60% 0₂ inhalation (range 5–35 beats min?^l HR_peak increase) was greatest in subjects with low HR_peak. HR responses to /?-l blockade increased as a function of HR_peak and the HR responses to atropine were the least in subjects with high HRpeak- These findings suggest that (a) the reduction in HR_peak is linked to the duration and severity of the hypoxaemia, (b) the degree of restoration of HR_peak with acute normoxia is dependent on the level of attenuation or down-regulation of cardiac sympathetic activation (SNA), (c) cardiac vagal drive is masked to a lesser extent in chronic hypoxia because of attenuated SNA and lower HR_peak values, and (d) the lower blood lactate levels at altitude is a function of muscle mass involvement rather than adrenergic activation, as normal peak values were reached during exercise with a small muscle mass.     

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.     

Acute blockade of β1-receptors in the asphyxiated sheep fetus

Acute blockade of β₁-receptors in the asphyxiated sheep fetus. Acta Physiol Scand 130 , 381–385. Received 5 November 1986, accepted 9 February 1987. ISSN 0001–6772. Department of Paediatrics, Landspitalinn, University Hospital, Reykjavik, Iceland and Department of Physiology and Department of Paediatrics I, University of Goteborg, Sweden. The effects of acute β₁-blockade on fetal cardiovascular reactions during asphyxia were evaluated in 11 exteriorized sheep fetuses. Gestational age was 110–142 days. Asphyxia was induced either by ventilating the mother with low oxygen gas mixture or by mechanical reduction of placental blood flow. During asphyxia all fetuses reacted to metoprolol injection with a decrease in heart rate, myocardial contractility, cardiac output and arterial blood pressure. Five experiments resulted in irreversible fetal cardiovascular collapse. Isoprenaline was given to the fetuses during hypoxia to test the ability to further increase heart rate and activate myocardial β-adrenoceptors. In those experiments with fetal cardiovascular demise after metoprolol, the isoprenaline injection did not result in a significant tachycardia. The surviving fetuses could increase their heart rate as a sign of a capacity to further increase the sympatho-adrenergic drive.     

Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy subjects

The application of an orthostatic stress such as lower body negative pressure (LBNP) has been proposed to minimize the effects of weightlessness on the cardiovascular system and subsequently to reduce the cardiovascular deconditioning. The KAATSU training is a novel method to induce muscle strength and hypertrophy with blood pooling in capacitance vessels by restricting venous return. Here, we studied the hemodynamic, autonomic nervous and hormonal responses to the restriction of femoral blood flow by KAATSU in healthy male subjects, using the ultrasonography and impedance cardiography. The pressurization on both thighs induced pooling of blood into the legs with pressure-dependent reduction of femoral arterial blood flow. The application of 200 mmHg KAATSU significantly decreased left ventricular diastolic dimension (LVDd), cardiac output (CO) and diameter of inferior vena cava (IVC). Similarly, 200 mmHg KAATSU also decreased stroke volume (SV), which was almost equal to the value in standing. Heart rate (HR) and total peripheral resistance (TPR) increased in a similar manner to standing with slight change of mean blood pressure (mBP). High-frequency power (HF_RR) decreased during both 200 mmHg KAATSU and standing, while low-frequency/high-frequency power (LF_RR/HF_RR) increased significantly. During KAATSU and standing, the concentration of noradrenaline (NA) and vasopressin (ADH) and plasma renin activity (PRA) increased. These results indicate that KAATSU in supine subjects reproduces the effects of standing on HR, SV, TPR, etc., thus stimulating an orthostatic stimulus. And, KAATSU training appears to be a useful method for potential countermeasure like LBNP against orthostatic intolerance after spaceflight.     

Acute blockade of beta 1-receptors in the asphyxiated sheep fetus

The effects of acute beta 1-blockade on fetal cardiovascular reactions during asphyxia were evaluated in 11 exteriorized sheep fetuses. Gestational age was 110-142 days. Asphyxia was induced either by ventilating the mother with low oxygen gas mixture or by mechanical reduction of placental blood flow. During asphyxia all fetuses reacted to metoprolol injection with a decrease in heart rate, myocardial contractility, cardiac output and arterial blood pressure. Five experiments resulted in irreversible fetal cardiovascular collapse. Isoprenaline was given to the fetuses during hypoxia to test the ability to further increase heart rate and activate myocardial beta-adrenoceptors. In those experiments with fetal cardiovascular demise after metoprolol, the isoprenaline injection did not result in a significant tachycardia. The surviving fetuses could increase their heart rate as a sign of a capacity to further increase the sympatho-adrenergic drive.