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.

     

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.

     

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 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.

     

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.

     

Focal microdialysis of CO2 in the perifornical-hypothalamic area increases ventilation during wakefulness but not NREM sleep

We investigated whether the perifornical-lateral hypothalamic area (PF-LHA), where the orexin neurons reside, is a central chemoreceptor site by microdialysis of artificial cerebrospinal fluid (aCSF) equilibrated with 25% CO₂ into PF-LHA in conscious rats. This treatment is known to produce a focal tissue acidification like that associated with a 6–7 mm Hg increase in arterial P_CO2$P_{C{O}_2}$. Such focal acidification in the PF-LHA significantly increased ventilation up to 15% compared with microdialysis of normal aCSF equilibrated with 5% CO₂ only in wakefulness but not in sleep in both the dark (P = 0.004) and light (P < 0.001) phases of the diurnal cycle. This response was predominantly due to a significant increase in respiratory frequency (11%, P < 0.001). There were no significant effects on ventilation in the group with probes misplaced outside the PF-LHA. These results suggest that PF-LHA functions as a central chemoreceptor site in the central nervous system in a vigilant state dependent manner with predominant effects in wakefulness.     

A continuous wave doppler velocimeter for monitoring blood flow in the popliteal artery,compared with venous occlusion plethysmography of the calf

Central respiratory drive responding to pH changes was eliminated by bilateral coagulation or cold block of area S (intermediate area) on the ventral medullary surface in 7 anaesthetized cats. Arterial pH,PCO₂, andPO₂ (4 cats) and the respiratory response to hypoxia and hypercapnia (6 cats) were observed before and after coagulation. After coagulation in hyperoxia the arterial pH dropped from 7.30 to 7.09, the arterialPCO₂ was elevated from 4.80 kPa to 8.17 kPa (6 cats). Ventilation increased by 477 ml at aPCO_2a of 6.58 kPa whenPO_2a was reduced from 39.5 kPa to 8.5 kPa before coagulation, after coagulation ventilation increased by 241 ml (4 cats). The peripheral chemoreceptors guaranteed spontaneous breathing even in hyperoxia. The data reveal that the loss of respiratory homeostasis by elimination of the S areas is due to the loss of central chemosensitive drive with concomitant reduction of peripheral chemoreceptor effect.Supported by the Deutsche Forschungsgemeinschaft SFB 114 Bionach     

Changes during eating in oxygen consumption, cardiac function and body fluids of sheep

1. A study was made of the changes taking place in O₂ consumption, cardiac function and the volume and composition of the body fluids of sheep while they consumed a meal of hay.

2. During eating P_{a, CO2} and P_{v, CO2} both increased, pH decreased and free plasma [HCO₃^-] increased. Venous haematocrit increased sharply at the beginning of the meal, and declined slowly after feed was removed.

3. Arterial P_O2 did not change significantly during eating. However P_{v, O2} fell slightly but significantly. The O₂ saturation of venous blood fell due to the decline in pH. Estimated CO₂ in arterial blood increased as a consequence of increased haemoglobin content. The net effect was to increase arteriovenous difference in O₂ content from 4·4 ml./100 ml. before eating to 6·0 ml./100 ml. at the end of the meal.

4. O₂ consumption increased about 60% during eating and fell rapidly thereafter. Heart rate followed a similar pattern. Cardiac output however increased only about 17%, from 6 to 7 l./min. Consequently stroke volume declined throughout the meal from 76 to 52 ml./beat.

5. Plasma volume, estimated from measurements of T-1824, declined sharply by about 300 ml. at the beginning of the meal and recovered slowly after feed was removed. Blood volume declined less because of a rise in circulating erythrocytes.

6. Extracellular fluid volume was estimated from measurements of thiocyanate and thiosulphate spaces. Thiocyanate space measurements were abandoned after thiocyanate was found to be concentrated in saliva. Considerable random variation occurred in measurements of changes in extracellular fluid from thiosulphate disappearance but the results did reveal a significant fall of 1000-1500 ml. in extracellular fluid volume during eating.

7. The significance of these interrelated changes is discussed in relation to the maintenance of homoeostasis during eating in the sheep.

     

Über die Wirkung der Pressoreceptoren des Carotisgebiets der narkotisierten Katze auf die Atmung nach isolierter Ausschaltung der Chemoreceptoren

1. In 5 cats ligthly anesthetized with chloralose-urethane all chemoreceptor response was abolished by cutting the vagosympathetic trunks including depressor nerves and by embolization of the carotid bodies by lycopodium powder. By means of a pressurized bottle attached to the femoral arteries mean arterial pressure was regulated to three different levels (160, 120 and 80 Torr consecutively) and was kept constant at each of these levels. Transients and steady state values of ventilation were recorded during this stepwise change of blood pressure. The effect on ventilation of severing sinus nerves at constant blood pressure was observed.After severing sinus nerves recording of the effect of blood pressure changes on ventilation was repeated.2. In this preparation (chemoreceptors denervated, carotid pressoreceptors intact) severing sinus nerves is followed by a diminution of ventilation in the same order of magnitude as described in the preceding papers, even if blood pressure is kept constant.3. Following stepwise diminution of mean arterial pressure in the chemodenervated cat, ventilation returns to its initial value after a transient increase. This confirms the conclusion of the preceding paper that during steady state no tonic influence of pressoreceptors on ventilation can be observed.4. The transient increase of ventilation following diminution of blood pressure is less pronounced, but not abolished, after severing the sinus nerves. It is therefore considered to be only partly due to the release of an inhibition by pressoreceptor impulses. The remaining effect must be due to other causes, possibly transient change of cerebral circulation.5. From this evidence and that from the preceding papers it must be concluded that the steady state decrease of ventilation observed after severing sinus nerves in cats inhaling gas mixtures containing 35 or 99% O₂ can not be attributed either to chemoreceptor drive by O₂ deficiency or to blood pressure effects on chemo—or pressoreceptors. Effects of CO₂ or H⁺ on chemoreceptors can be excluded as well since in the experiments of this paper all chemoreceptor drive is abolished.It must therefore be concluded that an unknown respiratory drive is depending upon the integrity of the sinus nerves.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Vergleich der Wirkung verschiedener Acidosen (NH4Cl,CaCl2, Acetazolamid) auf die Lungenbelüftung beim Menschen

Summary In seven healthy subjects acidosis was induced by NH₄Cl, by CaCl₂ or by acetazolamide (diamox). The response of respiratory minute volume to inhaled CO₂ mixtures was studied in control and acidosis experiments. The arterial and endexpiratory CO₂-tensions were determined simultaneously. The respiratory minute volumes were plotted against arterial or alveolar CO₂ tensions (CO₂ response curve). By interpolation in the CO₂ response curves the lung ventilation in acidosis and in the control experiment could be compared at equal CO₂ tensions.1. Conclusions obtained with endexpiratory and with arterial CO₂ tension measurements were coinciding.2. The mean slope of the curves describing the dependance of lung ventilation upon arterial CO₂ tension was not significantly altered in acidosis. The effect of acidosis is a parallel shift of the curve to higher ventilation or lower CO₂ tension.3. No significant difference in the response of lung ventilation to acidosis could be detected between NH₄Cl, CaCl₂ or acetazolamide acidosis.4. If ventilations at equal CO₂ tensions were compared, the effect of acidosis on lung ventilation was found to be in the average 2.01 min^–1 per –0.01 p _h change or 2.7 l min^–1 per –1 meq l^–1 change of whole blood buffer base.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.

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Die Versuchsergebnisse waren Gegenstand eines Vortrags auf der Tagung der Deutschen Physiologischen Gesellschaft in Bad Nauheim im Mai 1959.

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Fräulein C. v. Rath und Frau C. Voges danken wir für unermüdliche und sorgfältige Mitarbeit.

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Stipendiat der A. v. Humboldt-Stiftung.     

A dual control system for assisting respiration

A dual control system for assisting respiration was developed. The following features were included: (i) ventilation is controlled by the metabolic rate from continuously measured CO₂ output, (ii) physiologic dead space approximated as a linear function of tidal volume is used to estimate alveolar ventilation, and (iii) oxygen concentration in the inspired gas is regulated by the arterial oxygen saturation continuously measured with an ear oximeter. The ventilator was used on dogs with an inspired gas mixture of 85% N₂ and 15% O₂. Arterial P_co2 was maintained between 36 and 39 mmHg for a duration exceeding 60 minutes. Although an oscillatory variation was seen in the arterial P_o2 due to the adoption of an on-off control mode to regulate the O₂ fraction in the inspired gas, it remained between 80 and 136 mmHg. The dual control system of assisting respiration is capable of maintaining both the arterial P_co2 and P_o2 within normal levels at any level of metabolic rate and any respiratory frequency.     

Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve

1. The innervation of carotid body Type I cells has been investigated in seventeen cats. At a sterile operation the glossopharyngeal and vagus nerve roots were cut intracranially on one side.

2. From 1½ to 378 days after the operation the carotid bodies were fixed in situ and prepared for electron microscopy. Nerve endings on Type I cells were found to degenerate with a prolonged time course. In each cat there was a decrease in the number of nerve endings on the operated side as compared with the non-operated side.

3. Before the carotid bodies were fixed, recordings were made from chemoreceptor, and baroreceptor, afferent fibres in the sinus nerve on the operated side. The chemoreceptors responded in the usual way to changes in arterial O₂, CO₂ and pH; the injection of cyanide evoked a brisk response.

4. It is concluded that the nerve endings on Type I cells are efferent rather than afferent and the cell bodies of their axons are probably in the brain stem.

     

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.     

Ventilatory response to oscillating and non-oscillatingPa CO 2 in the anesthetized cat

Summary In 11 adult cats, lightly anesthetized with chloralose-urethane, blood from both common carotid arteries was led into a plastic chamber of 15–20 ml and returned to the carotids at a point 1.5 cm more cranial. By doing so arterial blood was assumed to pool within the chamber and lose itsP _{CO 2} oscillations which are normally known to exist as a result of the respiratory cycle. In control periods blood bypassed the chamber, thus maintaining respiratoryP _{CO 2} oscillations. Spontaneous ventilation was measured spirometrically. The animals were breathing pure O₂.Results. 1. When the sinus (carotid) nerves were intact or sectioned there was no significant difference in ventilation before or after switching from non-oscillating to oscillatingPa _{CO 2}. 2. When the vertebral arteries were ligated a drop in ventilation occurred after turning to oscillatingPa _{CO 2} which was followed by a slight rise above control values after 30–50 sec. This phenomenon was independent of sinus nerve integrity. Thus in hyperoxie condition the smallPa _{CO 2} oscillations known to occur in phase with respiration do not seem to provide a respiratory stimulus to resting ventilation above that generated by the mean level ofPa _{CO 2}. The ventilatory depression after vertebral artery ligation must at this time remain unexplained.     

Cardiovascular and respiratory reflexes of the gulf toadfish (Opsanus beta) during acute hypoxia

The acute cardiovascular and respiratory responses of the gulf toadfish, Opsanus beta, to acute hypoxia or exposure to the O₂ chemoreceptor stimulant, sodium cyanide (NaCN) were characterized and the role of serotonin type 2 (5-HT₂) receptors in mediating these responses was investigated. Toadfish responded to hypoxia or NaCN exposure with a decrease in heart rate (fH) and an increase in breathing amplitude (V_AMP) but no change in breathing frequency (fR). The bradycardia appeared to be mediated to some extent by 5-HT₂ receptors, as methysergide, a non-selective 5-HT_1/2 receptor antagonist, and ketanserin, a 5-HT₂ receptor antagonist, attenuated the response. Injection of α-methyl-5-HT, a 5-HT₂ agonist, also resulted in bradycardia that was inhibited by ketanserin, lending further support for 5-HT₂ receptor involvement, possibly 5-HT_2A or 5-HT_2C, in the regulation of fH. External NaCN exposure resulted in a significant decrease in caudal arterial blood pressure (P_CA) that was attenuated by methysergide. In contrast, injection with α-methyl-5-HT resulted in a substantial increase in P_CA that was not affected by ketanserin, suggesting the possible involvement of 5-HT_2B or 5-HT_2C receptors. These data are the first to suggest a unique distribution of 5-HT_2B/2C receptors may be involved in mediating vasoconstriction of the systemic vasculature of toadfish. These data also provide mechanistic support for why pulsatile urea excretion, believed to be regulated by 5-HT via the toadfish 5-HT_2A receptor, is not triggered by hypoxia or external chemoreceptor activation.     

Alveolar to arterial transmission of oxygen fluctuations due to respiration in anesthetized dogs

Summary The amplitudes of respiratory oxygen fluctuations in the alveoli obtained by calculation were compared with those of the arterial blood measured by a catheterP _{O 2} electrode in vivo in anesthetized and artificially ventilated dogs. It is shown that there is a significant correlation between them in general in bothP _{O 2} andS _{O 2} though the latter correlates better. Amplitude ratio of arterial to alveolar O₂ fluctuations was calculated from two factors, i.e., dispersion of circulation time in the pulmonary vein and mixing in the left heart. The results of calculation agree satisfactorily with those obtained experimentally. The reduction of the amplitude of respiratory fluctuations of oxygen seems to be quite small in the aorta.     

Insights into the evolution of polymodal chemoreceptors

Respiratory chemoreceptors in vertebrates are specialized cells that detect chemical changes in the environment or arterial blood supply and initiate autonomic responses, such as hyperventilation or changes in heart rate, to improve O₂ uptake and delivery to tissues. These chemoreceptors are sensitive to changes in O₂, CO₂ and/or H⁺. In fish and mammals, respiratory chemoreceptors may be additionally sensitive to ammonia, hypoglycemia, and numerous other stimuli. Thus, chemoreceptors that affect respiration respond to different types of stimuli (or modalities) and are considered to be "polymodal". This review discusses the polymodal nature of respiratory chemoreceptors in vertebrates with a particular emphasis on chemoreceptors of the carotid body and pulmonary epithelium in mammals, and on neuroepithelial cells in water- and air-breathing fish. A major goal will be to examine the evidence for putative polymodal chemoreceptors in fish within the context of studies on mammalian models, for which polymodal chemoreceptors are well described, in order to improve our understanding of the evolution of polymodal chemoreceptors in vertebrates, and to aid in future studies that aim to identify putative receptors in air- and water-breathing fish.     

Combined action of hypoxia and hypercapnia on functional state of the respiratory center

Discharges of bulbar respiratory neurons and electrical activity of the diaphragm and intercostal muscles were studied and pO₂, pCO₂, pH, and the oxygen saturation of the arterial blood were determined in cats anesthetized with pentobarbital and exposed to the combined action of hypoxia and hypercapnia. During inhalation of a hypoxic gas mixture the developing hypocapnia disturbed the firing pattern of the respiratory neurons and respiration of the Cheyne-Stokes type was established. Addition of 2% CO₂ to the hypoxic gas mixture restored the arterial blood gas composition to its initial level, prevented the development of hypocapnia, and prevented the disturbance of the rhythmic firing pattern of the respiratory neurons. Addition of 5% CO₂ to the hypoxic gas mixture had a negative action: respiratory unit activity was first stimulated, then inhibited, metabolic and respiratory acidosis was induced, and asphyxia developed.     

Wirkung der Bicarbonat-Alkalose auf die Lungenbelüftung beim Menschen Bestimmung der Teilwirkungen vonph und CO2-Druck auf die Ventilation und Vergleich mit den Ergebnissen bei Acidose

Summary 1. In human subjects metabolic alcalosis was induced by 0,5 g/kg NaHCO₃. Gas mixtures of about 0, 2, 4, and 6% CO₂, 35% O₂ in N₂ were inhaled, and the response of respiratory minute volume to variation of alveolar (arterial)pco ₂ was determined. Alveolarpco ₂ was read as endtidalpco ₂ from an infrared analyzer record. During inhalation of each gas mixture samples of arterial blood were taken from an indwelling needle in the femoral artery. CO₂ content, O₂ content, O₂ capacity andph were determined with routine methods.pco ₂ and whole blood buffer base were calculated.2. In alcalosis the curve describing the dependance of respiratory minute volume upon alveolarpco ₂ was shifted to higherpco ₂ in comparison to the control experiments in an approximately parallel way. The shift perph unit, however, was smaller than was found in earlier experiments on acidosis with similar methods. This indicates that the partialph sensitivity of respiration is diminishing in the alcaline range.3. The data were used together with already published data on metabolic acidosis to draw isoventilatory lines in apco ₂-ph diagramm which allows to isolate the partialpco ₂ andph effects and gives a more general information on the dependance of lung ventilation upon the parameters of acid base equilibrium.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.

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Stipendiat der Alexander v. Humboldt-Stiftung.

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Adr. Med. Klinik d. Freien Universität Berlin.

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Adr. Physiol. Institut d. Universität Heidelberg.