Cardiovascular effects of hyperbaric oxygen with and without addition of carbon dioxide

It is commonly believed that during hyperbaric oxygen (HBO) treatment, in spite of the vasoconstriction induced by the increased O₂ content in the breathing gas, the elevated carrying capacity of O₂ in the arterial blood results in augmented O₂ delivery to tissues. The experiments described here tested the hypothesis that HBO treatment would be more efficient in delivering O₂ to poorly perfused tissues if the vasoconstriction induced by elevated O₂ could be abolished or attenuated by adding CO₂ to the breathing gas. Organ blood flow (Q˙ _OBF), systemic hemodynamics, and arterial blood gases were measured before, during and after exposure to either 300?kPa O₂ (group 1) or 300?kPa O₂ with 2?kPa CO₂ (group 2), in awake, instrumented rats. During the HBO exposure the respiratory frequency (f _b) fell (4 breaths?·?min^?1?·?100?kPa O₂ ^?1), with no changes in arterial CO₂ tension (P _aCO₂), but when CO₂ was added, f _b and P _aCO₂ increased. The left ventricular pressure (LVP) and the systolic arterial pressure (SBP) increased. The maximum velocity of LVP (+dP/dt) rose linearly with LVP whether CO₂ was added or not (r ²?=?0.72 and 0.75 respectively). Similarly, the cardiac output (Q˙ _c) and heart rate (f _c) fell, while the stroke volume (SV) was unaltered, independent of P _aCO₂. There was a general vasoconstriction in most organs in both groups, with the exception of the central nervous system (CNS), eyes, and respiratory muscles. HBO reduced the blood flow to the CNS by 30%, but this vasoconstriction was diminished or eliminated when CO₂ was added. In group 2, the blood flow to the CNS rose linearly with increased P _aCO₂ and decreased pH. After decompression f _c and SBP stayed high, while Q˙ _c returned to control values by reducing the SV; CNS blood flow remained markedly elevated in group 2, while in group 1, it returned to control levels. We conclude that the changes in f _c, Q˙ _c, LVP, dP/dt, SBP and most Q˙ _OBF values induced by HBO were not changed by hypercapnia. Blood flow to the CNS decreased during HBO treatment at a constant P _aCO₂. Hypercapnia prevented this decline. Elevated P _aCO₂ augmented O₂ delivery to the CNS and eyes, but increased the susceptibility to O₂ poisoning. A prolonged suppression of O₂ supply to the CNS occurred during the HBO exposure and in air following the decompression in the absence of CO₂. This suppression was offset by the addition of CO₂ to the breathing gas.     

The blood flow and oxygen consumption of brown adipose tissue in the new-born rabbit

1. A direct method for measuring venous outflow from brown adipose tissue in anaesthetized new-born rabbits is described.

2. During noradrenaline infusion the mean blood flow through brown adipose tissue increased from 87 to 360 ml./100 g tissue (wet wt.).min, and the mean rate of oxygen consumption of brown adipose tissue rose from 9·3 to 60 ml. O₂/100 g tissue.min.

3. During cold exposure the mean blood flow through brown adipose tissue increased from 90 to 304 ml./100 g tissue.min.

4. The mean cardiac output was 266 ml./kg body weight.min; during noradrenaline infusion it was 405 ml./kg body weight.min. At rest about one tenth, and during noradrenaline infusion about one quarter of the cardiac output went to brown adipose tissue.

5. It was calculated that most of the extra oxygen consumed during the metabolic response of the anaesthetized new-born rabbit to noradrenaline infusion or cold exposure was consumed by brown adipose tissue.

6. Hypoxia (breathing 10% O₂ in N₂) greatly reduced the increase in oxygen consumption but not the increase in blood flow in brown adipose tissue caused by noradrenaline infusion.

     

Observations on the rhythmic variation in the cat carotid body chemoreceptor activity which has the same period as respiration

1. The activity in carotid body chemoreceptor afferent fibres in the cat has been recorded and found to have a rhythm with the same period as respiration.

2. This rhythm is not an artifact; it is not due to arterial pressure changes with respiration nor to cyclical changes in pulmonary venous admixture. It is caused by changes in blood gas tensions during each respiratory cycle.

3. The amplitude of the rhythm is modified by transient and long-term changes in inspired oxygen or CO₂ so that a rise or fall in O₂ or CO₂ tensions of arterial blood (P_a,O2, P_a,CO2) from the physiological range reduces it. The ratio of the rhythm amplitude to the mean rate of chemoreceptor discharge increases with P_a,O2 over the range 40-240 mm Hg.

4. The rhythm is modified by changes in respiratory frequency and volume.

5. The fluctuations of arterial oxygen tension which have the same period as respiration are shown to be conducted up the vertebral artery at least as far as the vertebro-occipital anastomosis.

6. It is proposed that the chemoreceptor rhythm reflects the moment to moment changes in blood gas tensions.

     

Maternal hyperventilation and foetal hypocapnia in sheep

1. In anaesthetized foetal lambs near term, hypocapnia induced by maternal hyperventilation abolished the rise of arterial pressure and femoral vasoconstriction caused by hypoxaemia. This is consistent with interaction of P_CO2 and P_O2 on the foetal aortic bodies.

2. In immature lambs (0·6-0·77 of term) maternal hyperventilation caused a fall in foetal carotid P_CO2 commensurate with that in the maternal blood. In mature lambs (at 0·9 or more of term) the fall in foetal carotid P_CO2 was less than that in maternal blood, whether the foetus was exteriorized or in utero.

3. The mean transplacental gradient for P_CO2 (maternal arterial-umbilical vascular), when the foetus was replaced with a mechanical pump recirculating foetal blood, was 6·3 mm Hg. This is attributed to placental CO₂ production, and is nearly half the mean P_CO2 gradient (maternal artery-foetal carotid) of about 14 mm Hg during normal maternal ventilation.

4. The mean maternal-umbilical transcotyledonary venous gradients (avoiding vascular shunts through the myometrium and intercotyledonary chorion) were for P_CO2 1·7 mm Hg and for P_O2 13·4 mm Hg.

5. Maternal hyperventilation (P_{a, CO2} ~ 20 mm Hg) caused a small fall in mean foetal carotid P_O2 (5 mm Hg), which was readily reversible with no evidence of progressive acidaemia.

     

The effect of carotid body denervation upon the respiratory response to hypoxia and hypercapnia in the duck

1. Respiratory responses to altered P_{a, O2} at constant P_{a, CO2} and altered P_{a, CO2} at constant P_{a, O2} were measured in fourteen unanaesthetized ducks 5-9 weeks old.

2. All the ducks responded to the inhalation of a few breaths of 100% O₂ with a fall in _E of between 11 and 17% of control, and to the reduction in P_{a, O2} from control levels (93-101 mm Hg) to 38-47 mm Hg with an average increase in _E of 190% of control which was potentiated by raising the level of CO₂.

3. Ventilation approximately doubled when P_{a, CO2} was raised to 55 mm Hg, the greatest sensitivity to changes in P_{a, CO2} being over the range 40-45 mm Hg.

4. Carotid body denervation was carried out in nine ducks and the respiratory responses were modified. The fall in _E with inhalation of 100% O₂ was abolished in all ducks and the rise in _E with hypoxia was abolished in six. The increase in _E as P_{a, CO2} was altered in steps was unaffected but the rate at which _E increased in response to 4% CO₂ was markedly reduced.

5. It is concluded that the chemoreceptor regulation of respiration in ducks is similar to that observed in non-diving animals.

     

The respiratory response of the new-born lamb to inhaled CO-2 with and without accompanying hypoxia

1. The respiratory response to inhaled CO₂ was measured in twenty unanaesthetized new-born lambs aged 4 hr-10 days. Measurement of resting arterial pH, P_CO2 and plasma bicarbonate showed a non-respiratory acidosis immediately after birth which was corrected in the first 24-28 hr: thereafter, the acid—base pattern was of a compensated respiratory alkalosis.

2. When CO₂ was added to the inspired gases and resting arterial oxygen tension (P_a, _O2) was controlled, the average increase in minute ventilation () was 0·075 l.min^-1.kg^-1.mm Hg, P_a, _CO2^-1 and duplicate responses in the same lamb differed by 6-22·5%.

3. The slope of the /P_a, _CO2 line (S) varied inversely with P_a, _O2. In one lamb, severe hypoxia (P_a, _O2 = 21 mm Hg) caused a marked depression of the slope.

4. Neither the slope S nor the horizontal intercept B of the lines was related to the age of the lamb. B was not related to pH_a and only slightly affected by acute hypoxia. B was related to arterial [HCO₃^-] and values for both were reduced with the acid—base disturbances seen in the first 10 days after birth. Evidence was given which suggested that the response of the new-born lamb to inhaled CO₂ was similar to that of man acclimatized to a P_a, _O2 of 70-75 mm Hg.

5. In the lightly anaesthetized lamb, bilateral section of the sinus nerves caused a small reduction in the sensitivity to inhaled 5% CO₂ in air, an increase in the respiratory lag and a reduction in the rate at which increased.

6. It was concluded that, in the new-born lamb, the carotid chemo-receptors are involved in the response to inhaled CO₂ and that hypoxia potentiates this response.

     

Positive end expiratory pressure as a method for preventing acute mountain sickness

In order to study the use of positive end expiratory pressure (PEEP) to prevent acute mountain sickness (AMS), 22 subjects were exposed randomly to 8-h hypobaric hypoxia in a hypobaric chamber (4500?m, 589?hPa, 22°C) once being administered 5-cm H₂O PEEP and once without. The prevention of AMS by PEEP was evaluated by scoring AMS according to the Lake Louise system (self-report questionnaire and clinical assessment) throughout the experiment with O₂ saturation (SO₂) and heart rate measurements being made. Arterial blood analyses (partial pressures of arterial O₂ and CO₂, P _aO₂, P _aCO₂, and pH) were made at the end of the exposure. Results showed decreased AMS scores with PEEP at the end of the 8-h hypoxia [1.50 (SEM 1.32) vs 3.23 (SEM 2.07), P?P?SO₂, P _aO₂, P _aCO₂ and HCO₃ ^? did not change significantly. However, a smaller increase in arterial pH [7.47 (SEM 0.02) vs 7.50 (SEM 0.02), P?P?2O PEEP may help decrease AMS scores at the end of an 8-h exposure to hypoxia in a hypobaric chamber. Such a method could be used to prevent AMS in such experimental conditions without adverse effects.     

The reflex effects of alterations in lung volume on systemic vascular resistance in the dog

1. The reflex effects of alterations in lung volume on systemic vascular resistance have been studied in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow. The pressures in the isolated perfused carotid sinuses and aortic arch, and the arterial blood P_O2 and P_CO2 were maintained constant.

2. A maintained inflation of the lungs produced by injection of air into the trachea caused a fall in systemic arterial perfusion pressure, indicating vasodilatation. The size of the systemic vasodilator response varied directly with the pressure and volume of gas used to inflate the lungs. A similar effect was observed when the tidal volume of lungs ventilated by an intermittent positive pressure was increased.

3. Collapse of the lungs by creating a pneumothorax in closed-chest spontaneously breathing animals evoked a systemic vasoconstrictor response which was reversed when the lungs were re-expanded.

4. These vasodilator responses were abolished by dividing the pulmonary branches of the thoracic vagosympathetic nerves. Evidence is presented that the afferent fibres run in the cervical vagosympathetic nerves and through the stellate ganglia.

5. The responses were unaffected by atropine, but were abolished by hexamethonium, guanethidine and by bretylium tosylate, indicating that they are mediated via the sympathetic nervous system.

6. Evidence is presented that the lungs are a constant course of afferent impulses inhibiting the `vasomotor centre', and that the lung inflation—systemic vasodilator reflex is a potential mechanism operating in eupnoeic breathing.

     

Ventilatory efficiency and exercise tolerance in 101 healthy volunteers

The ventilatory equivalent for CO₂ defines ventilatory efficiency largely independent of metabolism. An impairment of ventilatory efficiency may be caused by an increase in either anatomical or physiological dead space, the latter being the most important mechanism in the hyperpnoea of heart failure, pulmonary embolism, pulmonary hypertension and the former in restrictive lung disease. However, normal values for ventilatory efficiency have not yet been established. We investigated 101 (56 men) healthy volunteers, aged 16–75 years, measuring ventilation and gas exchange at rest (n?=?64) and on exercise (modified Naughton protocol, n?=?101). Age and sex dependent normal values for ventilatory efficiency at rest defined as the ratio ventilation:carbon dioxide output (V˙ _E:V˙CO₂), exercise ventilatory efficiency during exercise, defined as the slope of the linear relationship between ventilation and carbon dioxide output (V˙ _E vs V˙CO₂ slope), oxygen uptake at the anaerobic threshold and at maximum (V˙O_2AT,V˙O_2max, respectively) and breathing reserve were established. Ventilatory efficiency at rest was largely independent of age, but was smaller in the men than in the women [V˙ _E:V˙CO₂ 50.5 (SD 8.8) vs 57.6 (SD 12.6) P<0.05]. Ventilatory efficiency during exercise declined significantly with age and was smaller in the men than in the women (men: (V˙ _E vs V˙CO₂ slope?= 0.13?×?age?+?19.9; women: V˙ _E vs V˙CO₂ slope?= 0.12?×?age?+?24.4). The V˙O_2AT and V˙O_2max were 23 (SD 5) and 39 (SD 7) ml O₂?·?kg?·?min^?1 in the men and 18 (SD 4) and 32 (SD 7) in the women, respectively, and declined significantly with age. The V˙O_2AT was reached at 58 (SD 9)% V˙O_2max. Breathing reserve at the end of exercise was 41% and was independent of sex and age. It was concluded from this study that ventilatory efficiency as well as peak oxygen uptake are age and sex dependent in adults.     

The effect of lung inflation on the control of respiratory frequency in the neonate

1. We have measured the relationship between tidal volume (V_T) and the duration of inspiration (T_i) and expiration (T_e) for individual breaths (30 in each steady state).

2. Ten pre-term and ten term infants were studied during steady state while breathing 21% O₂, then 21% O₂ plus 2 and 4% CO₂.

3. In all infants, the average T_i at the various chemical drives was remarkably constant, and did not decrease as the tidal volume increased. However, at any given level of respiratory drive, there was a slightly positive correlation of V_T with T_i and T_e in 95% of the cases.

4. In four pre-term and two term infants, T_e increased with increasing respiratory drive. In these infants, therefore, instantaneous respiratory frequency (1/(T_i + T_e)) actually decreased as lung volume increased.

5. We suggest that T_i is independent of V_T within the range of volumes studied (up to 2 times the resting V_T) and that changes in instantaneous respiratory frequency (1/(T_i + T_e)) result from changes in T_e.

     

Intracellular hyperhydration induced by a 7-day endurance race

A group of 15 competitive male cyclists [mean peak oxygen uptake, V˙O_2peak 68.5 (SEM 1.5?ml?· kg^?1?·?min^?1)] exercised on a cycle ergometer in a protocol which began at an intensity of 150?W and was increased by 25?W every 2?min until the subject was exhausted. Blood samples were taken from the radial artery at the end of each exercise intensity to determine the partial pressures of blood gases and oxyhaemoglobin saturation (S _aO₂), with all values corrected for rectal temperature. The S _a O₂ was also monitored continuously by ear oximetry. A significant decrease in the partial pressure of oxygen in arterial blood (P _aO₂) was seen at the first exercise intensity (150?W, about 40% V˙O_2peak). A further significant decrease in P _aO₂ occurred at 200?W, whereafter it remained stable but still significantly below the values at rest, with the lowest value being measured at 350?W [87.0 (SEM 1.9) mmHg]. The partial pressure of carbon dioxide in arterial blood (P _aCO₂) was unchanged up to an exercise intensity of 250?W whereafter it exhibited a significant downward trend to reach its lowest value at an exercise intensity of 375?W [34.5 (SEM 0.5) mmHg]. During both the first (150?W) and final exercise intensities (V˙O_2peak) P _aO₂ was correlated significantly with both partial pressure of oxygen in alveolar gas (P _AO₂, r?=?0.81 and r?=?0.70, respectively) and alveolar-arterial difference in oxygen partial pressure (P _A?aO₂, r?=?0.63 and r?=?0.86, respectively) but not with P _aCO₂. At V˙O_2peak P _aO₂ was significantly correlated with the ventilatory equivalents for both oxygen uptake and carbon dioxide output (r?=?0.58 and r?=?0.53, respectively). When both P _AO₂ and P _A?aO₂ were combined in a multiple linear regression model, at least 95% of the variance in P _aO₂ could be explained at both 150?W and V˙O_2peak. A significant downward trend in S _aO₂ was seen with increasing exercise intensity with the lowest value at 375?W [94.6 (SEM 0.3)%]. Oximetry estimates of S _aO₂ were significantly higher than blood measurements at all times throughout exercise and no significant decrease from rest was seen until 350?W. The significant correlations between P _aO₂ and P _AO₂ with the first exercise intensity and at V˙O_2peak led to the conclusion that inadequatehyperventilation is a major contributor to exercise-induced hypoxaemia.     

Latency to CNS oxygen toxicity in rats as a function of PCO2 and PO2

Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness, without any premonitory symptoms. We have made a quantitative study of the effect of inspired carbon dioxide on sensitivity to oxygen toxicity in the rat. Rats were exposed to four oxygen pressures (PO₂; 456, 507, 608 and 709?kPa) and an inspired partial pressure of carbon dioxide (PCO₂) in the range 0–12?kPa until the appearance of the electroencephalograph first electrical discharge (FED) that preceds the clinical convulsions. Exposures were conducted at a thermoneutral temperature of 27°C. Latency to the FED decreased linearly with the increase in PCO₂ at all four PO₂ values studied. This decrease, which is probably related to the cerebral vasodilatory effect of carbon dioxide, reached a minimal value that remained constant on further elevation of PCO₂. The slopes (absolute value) and intercepts of latency to the FED as a function of carbon dioxide decreased with the increase in PO₂. This log-linear relationship made possible the derivation of equations that describe latency to the FED as a function of both PO₂ and PCO₂ in the PCO₂– dependent range: Latency (min)?=?e^{(5.19?0.0040 P O2)}?e^{(2.77?0.0034 P O2)}?×?PCO₂ (kPa), and in the PCO₂-independent range: Latency(min) =?e^{(2.44?0.0009 P O2)}. A PCO₂ as low as 1?kPa significantly reduced the latency to the FED. It is suggested that in closed-circuit oxygen diving, any accumulation of carbon dioxide should be avoided in order to minimize the risk of CNS oxygen toxicity.     

Carbon dioxide storage and nonbicarbonate buffering in the human body before and after an Himalayan expedition

Before and 7–12 days after an Himalayan expedition CO₂ equilibration curves were determined in the blood plasma of 12 mountaineers by in vitro and in vivo CO₂ titration; in vivo osmolality changes (ΔOsm?·?ΔPCO₂ ^?1, ΔOsm?·?ΔpH^?1, where PCO₂ is the partial pressure of CO₂) during the latter experiments yielded estimates of whole body CO₂ storage. In vitro ?Δ[HCO₃ ^?]?·?ΔpH^?1 [nonbicarbonate buffer capacity (β) of blood] was increased 7 days after descent [before 31.3 (SEM 0.4) mmol?·?kgH₂O^?1, after?38.3?(SEM 3.9)?mmol?·?kgH₂O^?1; P<0.05] resulting from an increased proportion of young erythrocytes; in additional experiments an augmented β was found in young (low density cells) compared to old cells [<1.097 g?·?ml^?1: 0.216 (SEM 0.028) mmol?·?gHb^?1, >1.100?g?·?ml^?1: 0.145?(SEM 0.013)?mmol?·?gHb^?1, where Hb is haemoglobin; P<0.02]. In spite of increased Hb mass in vivo Δ[CO_2total]?·?ΔPCO₂ ^?1 [0.192?(SEM 0.010)?mmol?·?kgH₂O^?1?·?mmHg^?1] and ?Δ[HCO₃ ^?]?·?ΔpH^?1 [17.9?(SEM 1.0)?mmol?·?kgH₂O^?1] as indicators of extracellular β rose only slightly after altitude (7 days +16%, P<0.02; +7%, NS) because of haemodilution. The ΔOsm?·?ΔPCO₂ ^?1 [0.230?(SEM 0.015) mosmol?·?kgH₂O^?1?·?mmHg^?1] remained unchanged. Prealtitude differences in ΔOsm?·?ΔpH^?1 between hypercapnia [?41?(SEM 5)?mosmol?·?kgH₂O^?1] and hypo-capnia [?20?(SEM 3)?mosmol?·?kgH₂O^?1; P<0.01] disappeared temporarily after return since the former slope was reduced. The high value during hypercapnia before ascent probably resulted from mechanisms stabilizing intracellular pH during moderate hypercapnia which were attenuated after descent.     

The effects of hypoxia and CO2 on the sleep-waking pattern of the potoroo (Potorous tridactylus apicalis)

Four male potoroos (Potorous tridactylus apicalis) breathed 21% and 7% O₂ with and without the addition of 5% CO₂. The effects of these gas mixtures on the potoroo's sleeping-waking pattern (SWP) were studied. The SWP while breathing 21% O₂/5%CO₂ was unchanged when compared with that of breathing ambient air (21% O₂). While breathing 7% O₂, the SWP was severely disrupted: total sleep time (TST) and slow wave sleep (SWS) increased markedly. Brain temperature fell substantially. Paradoxical sleep (PS) was almost abolished and wakefulness (W) decreased. The addition of 5% CO₂ to the O₂ deficient gas mixture, i.e., 7% O₂/5% CO₂, restored the SWP to that obtained while breathing ambient air. It is concluded that CO₂ neutralizes the disruptive effect which hypoxia has on the potoroo's SWP. It is hypothesized that this constitutes a homeostatic mechanism for stabilizing the SWP and is carried over from pouch life.     

Über den Einfluß von CO2 auf die Bestandspotentiale der Hirnhäute

Summary In rabbits in light chloralose- urethane-anesthesia the arachnoid potential of the atlanto-occipital membrane on the respiratory minute volume were recorded simultaneously. Changes of potential and of respiratory minute volume with inhalation of CO₂ in air and of reduced O₂ in N₂ gas mixtures were observed.Inhalation of 5% CO₂ in air raised the arachnoid potential in the average 1.4 mV. In hypoxia the arachnoid potential decreased with the diminution of the CO₂-tension.5% CO₂ in air locally on the atlantooccipital membrane raises the arachnoid potential but not the respiratory minute volume.

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Vorgetragen auf Tagg. D. Physiol. Ges. Sept. 1955, Graz.     

The relative roles of the aortic and carotid sinus nerves in the rabbit in the control of respiration and circulation during arterial hypoxia and hypercapnia

1. The respiratory and circulatory effects of graded arterial hypoxia, alone or with superadded hypercapnia, were studied in four groups of unanaesthetized rabbits including normal animals and those with selective section of the aortic nerves, selective section of the carotid sinus nerves and section of both sets of nerves.

2. When measured 2-4 days after selective section of the carotid sinus nerves the resting respiratory minute volume and arterial P_O2 were lower and the P_CO2 higher than normal. These effects were not observed after selective section of the aortic nerves. Selective aortic nerve section, and selective carotid sinus nerve section each produced a similar increase in the resting arterial pressure and heart rate, but were without effect on the resting cardiac output.

3. During arterial hypoxia reflex respiratory and circulatory effects ascribable to arterial chemoreceptor stimulation (hyperventilation, bradycardia, vasoconstriction) were mediated for the most part through the carotid sinus nerve. In animals with only the aortic nerves intact the circulatory response was determined largely by the opposing effects of aortic baroreceptor reflexes and the local peripheral dilator action of hypoxia.

4. The circulatory effects of hyperventilation induced by hypercapnia during arterial hypoxia, in animals with both aortic and carotid sinus nerves cut were small.

5. The results suggest that relatively few chemoreceptor fibres originate from the aortic region in the rabbit, though the carotid sinus and aortic nerves both contain baroreceptor fibres.

     

Effects of severe arterial hypocapnia on regional blood flow regulation,tissuePO2 and metabolism in the brain cortex of cats

The effect of a stepwise decrease inPaCO₂ from 3.9–1.6 kPa on rCBF, rCMRO₂, tissuePO₂ and concentrations of glucose, lactate, pyruvate, ATP, ADP, AMP and phosphocreatine in the brain cortex was studied in cats lightly anaesthetized with sodium pentobarbital. 1. Moderate lowering ofPaCO₂ to 2.5 kPa induced in all animals a homogeneous decrease of rCBF in corresponding areas of the right and left hemisphere. Mean rCBF fell from 129.2 to 103.1 ml · 100 g^–1 · min^–1, while rCMRO₂ remained unchanged (12.7–12.9 ml · 100 g^–1 · min^–1). The tissuePO₂ frequency histograms showed a shift to lower values without indicating the presence of brain tissue hypoxia. 2. Severe arterial hypocapnia (PaCO₂=1.6 kPa) caused an inhomogeneous blood flow reaction. Both further decreased as well as increased rCBF values were measured simultaneously in the brain cortex of individual animals (mean rCBF=97.6 ml · 100 g^–1 · min^–1). At the same time tissuePO₂ measurements and metabolite assays indicated the presence of pronounced brain tissue hypoxia. The tissue concentrations of lactate and pyruvate and the lactate/pyruvate ratio were significantly increased, while the phosphocreatine concentration was significantly reduced. In addition, rCMRO₂ decreased to 11.3 ml · 100 g^–1 · min^–1. The results provide conclusive evidence that severe arterial hypocapnia leads to an insufficient O₂ supply of the brain cortex, which in turn seems to counteract the influence of hypocapnia on cortical blood flow regulation.Preliminary reports of these investigations were presented at the International Symposium on Oxygen Transport to Tissue, July 9–11, 1980 in Budapest and at the Second International Symposium on Pathophysiology and Pharmacotherapy of Cerebrovascular Disorders, July 22–25, 1980 in Tübingen, FRG     

Effects of indomethacin and polyunsaturated fatty acid diet on exercise-induced hypoxaemia in master athletes

We have previously reported a reduction in exercise-induced hypoxaemia following polyunsaturated fatty acid supplementation (PUFA). Although this might have been explained by increases in membrane fluidity, a clear explanation could not be provided due to potentially confounding influences of series-2 prosta- glandin mediated effects resulting from PUFA. In this investigation, ten master athletes [mean age 48.1 (SEM 6) years, maximal oxygen uptake (V˙O_{2 max} ) 3.39 (SEM 0.21) l?·?min^?1] completed a maximal cycling test (Ctrl) which was repeated after the administration of 150 mg of indomethacin to inhibit prostaglandin synthesis, both before and after 6 weeks of 3.66-g PUFA?·?day^?1. Cardiorespiratory parameters were obtained simultaneously with brachial arterial blood sampling for partial pressure of oxygen in arterial blood (P _aO₂), partial pressure of carbon dioxide in arterial blood (P _aCO₂), pH, oxygen saturation in arterial blood and lactate concentration determinations. A significant decrease in P _aO₂ (mmHg) from rest [93 (SEM 1.5)] was observed for exercise intensities of more than 40% V˙O_{2 max} in Ctrl reaching 75.9 (SEM 2.1) at V˙O_{2 max} . PUFA resulted in a 5.0 (SEM 0.68) mmHg upward shift (P?P _aO₂–oxygen uptake relationship, reducing the difference in partial pressure of oxygen between alveolar air and arterial blood (P _(A?a)O₂) at V˙O_{2 max} [Ctrl 36 (SEM 1.6) vs PUFA 33 (SEM 2.2) mmHg] while P _aCO₂, remained unchanged. Indomethacin had no effect on either P _aO₂, ideal partial pressure of oxygen in alveolar gas or P _(A?a)O₂ in either Ctrl or after PUFA. In contrast, the fall in pH was significantly reduced after indomethacin while V˙CO₂, P _aCO₂ and lactacidaemia remained unchanged. These observations confirm an effect of PUFA on exercise P _aO₂ behaviour which does not appear to be mediated by the influence of a series-2 prostaglandin.     

Metabolic and cardioventilatory responses during a graded exercise test before and 24 h after a triathlon

Previous studies have reported respiratory, cardiac and muscle changes at rest in triathletes 24?h after completion of the event. To examine the effects of these changes on metabolic and cardioventilatory variables during exercise, eight male triathletes of mean age 21.1 (SD 2.5) years (range 17–26 years) performed an incremental cycle exercise test (IET) before (pre) and the day after (post) an official classic triathlon (1.5-km swimming, 40-km cycling and 10-km running). The IET was performed using an electromagnetic cycle ergometer. Ventilatory data were collected every minute using a breath-by-breath automated system and included minute ventilation (V˙ _E), oxygen uptake (V˙O₂), carbon dioxide production (V˙CO₂), respiratory exchange ratio, ventilatory equivalent for oxygen (V˙ _E/V˙O₂) and for carbon dioxide (V˙ _E/V˙CO₂), breathing frequency and tidal volume. Heart rate (HR) was monitored using an electrocardiogram. The oxygen pulse was calculated as V˙O₂/HR. Arterialized blood was collected every 2 min throughout IET and the recovery period, and lactate concentration was measured using an enzymatic method. Maximal oxygen uptake (V˙O_{2 max} ) was determined using conventional criteria. Ventilatory threshold (VT) was determined using the V-slope method formulated earlier. Cardioventilatory variables were studied during the test, at the point when the subject felt exhausted and during recovery. Results indicated no significant differences (P>0.05) in V˙O_{2 max} [62.6 (SD 5.9) vs 64.6 (SD 4.8) ml?·?kg^?1?·?min^?1], VT [2368 (SD 258) vs 2477 (SD 352) ml?·?min^?1] and time courses of V˙O₂ between the pre- versus post-triathlon sessions. In contrast, the time courses of HR and blood lactate concentration reached significantly higher values (P<0.05) in the pre-triathlon session. We concluded that these triathletes when tested 24?h after a classic triathlon displayed their pre-event aerobic exercise capacity, bud did not recover pre-triathlon time courses in HR or blood lactate concentration.