Cardiovascular responses in apnoeic asphyxia: role of arterial chemoreceptors and the modification of their effects by a pulmonary vagal inflation reflex

1. In the spontaneously breathing anaesthetized dog, the systemic circulation was perfused at constant blood flow; there was no pulmonary blood flow and the systemic arterial blood P(O2) and P(CO2) were controlled independently by an extracorporeal isolated pump-perfused donor lung preparation. The carotid and aortic bodies were separately perfused at constant pressure with blood of the same composition as perfused the systemic circulation.2. Apnoeic asphyxia, produced by stopping the recipient animal's lung movements and, at the same time, making the blood perfusing the systemic circulation and the arterial chemoreceptors hypoxic and hypercapnic by reducing the ventilation of the isolated perfused donor lungs, caused an increase in systemic vascular resistance.3. While the systemic arterial blood was still hypoxic and hypercapnic, withdrawal of the carotid and aortic body ;drive' resulted in a striking reduction in systemic vascular resistance. Re-establishing the chemoreceptor ;drive' immediately increased the vascular resistance again.4. Apnoeic asphyxia carried out while the carotid and aortic bodies were continuously perfused with oxygenated blood of normal P(CO2) had little or no effect on systemic vascular resistance.5. The systemic vasoconstrictor response produced by apnoeic asphyxia was reduced or abolished by re-establishing the recipient animal's lung movements, and this effect occurred in the absence of changes in the composition of the blood perfusing the systemic circulation and arterial chemoreceptors. This abolition of the vasoconstriction was due to a pulmonary reflex.6. Apnoeic asphyxia slowed the rate of the beating atria due to excitation of the carotid and aortic body chemoreceptors. This response can be over-ridden by an inflation reflex arising from the lungs.7. It is concluded that the cardiovascular responses observed in apnoeic asphyxia are due, at least in part, to primary reflexes from the carotid and aortic body chemoreceptors engendered by arterial hypoxia and hypercapnia. The appearance of these responses is, however, dependent upon there being no excitation of a pulmonary (inflation) vagal reflex.     

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.

     

Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in the dog

1. In the anaesthetized dog the carotid sinuses and aortic arch were isolated from the circulation and separately perfused with blood by a method which enabled the mean pressure, pulse pressure and pulse frequency to be varied independently in each vasosensory area. The systemic circulation was perfused at constant blood flow by means of a pump and the systemic venous blood was oxygenated by an extracorporeal isolated pump-perfused donor lung preparation.2. When the vasosensory areas were perfused at non-pulsatile pressures within the normal physiological range of mean pressures, the reflex reduction in systemic vascular resistance produced by a given rise in mean carotid sinus pressure was significantly greater than that resulting from the same rise of aortic arch pressure.3. On the other hand, when the vasosensory areas were perfused at normal pulsatile pressures and within the normal physiological range of mean pressures, there was no difference in the size of the reflex vascular responses elicited by the same rise in mean pressure in the carotid sinuses and in the aortic arch.4. Whereas the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in pulse pressure, those evoked by the aortic arch baroreceptors through changes of mean pressure are only weakly affected by modifications in pulse pressure. Evidence for this was obtained from single stepwise changes of mean pressure in each vasosensory area during pulsatile and non-pulsatile perfusion, and from curves relating the mean pressure in the carotid sinuses or aortic arch and systemic arterial perfusion pressure.5. The vasomotor response elicited by combined stimulation of the carotid sinus and aortic arch baroreceptors was greater than either response resulting from their separate stimulation.6. When the mean perfusion pressures in the two vasosensory areas are changed together, the curve relating mean pressure to systemic arterial pressure during pulsatile perfusion of the areas is considerably flatter than that for non-pulsatile perfusion.7. Increasing the pulse pressure in the carotid sinuses or aortic arch caused a decrease in systemic vascular resistance, the response elicited from the carotid sinuses being the larger.8. Altering the phase angle between the pulse pressure waves in the carotid sinuses and aortic arch had no effect on systemic vascular resistance.9. In both vasosensory areas, increasing the pulse frequency caused a reduction in systemic vascular resistance.     

Effect of hypoxia on vascular responses to the carotid baroreflex.

The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.     

The contribution of the arterial chemoreceptors to the stimulation of respiration by adrenaline and noradrenaline in the cat

1. Intravenous infusions of adrenaline and noradrenaline in doses averaging 0.8 mug/kg.min increased the respiratory minute volume of anaesthetized cats breathing room air. The mean increase in respiratory minute volume was 14% during adrenaline infusion and 8% during noradrenaline infusion.2. In a small group of decerebrate cats infusions of adrenaline and noradrenaline increased ventilation by 19 and 27% respectively.3. Intravenous catecholamine infusions also increased the respiratory responses of anaesthetized animals to the inhalation of 5% or 10% O(2) in N(2) and to the inhalation of 5% CO(2) in air.4. Adrenaline and noradrenaline infusions had no significant effect on the ventilation of animals breathing 100% O(2), nor did they significantly alter the respiratory response to the inhalation of 5% CO(2) in O(2).5. After section of the carotid sinus and aortic nerves, a blood-pressure compensator being used to minimize changes in arterial pressure, catecholamines had no effect on the respiration of cats breathing air.6. An increase in carotid body chemoreceptor discharge accompanied the increase in ventilation during catecholamine infusion.7. Intravenous catecholamine infusions still produced an increase in ventilation and carotid body chemoreceptor discharge after both aortic nerves and both cervical sympathetic nerves had been cut.8. Intra-arterial infusions into one carotid artery of 0.2 mug/kg.min of adrenaline or 0.1 mug/kg.min of noradrenaline led to mean increases in respiratory minute volume of 9.9 and 11.5% respectively. No increase occurred after section of the corresponding carotid sinus nerve. Such infusions also evoked an increase in carotid body chemoreceptor discharge.9. It is concluded that the hyperpnoea produced by adrenaline and noradrenaline infusions in the cat is predominantly reflex in origin and is mediated by the arterial chemoreceptors.10. The increase in ventilation produced by adrenaline appears to have a component additional to its effect upon the chemoreceptors though the nature of this action has not been identified.     

The interaction of reflexes elicited by stimulation of carotid body chemoreceptors and receptors in the nasal mucosa affecting respiration and pulse interval in the dog

1. The effects on respiration and pulse interval of stimulation of the carotid body chemoreceptors before, during and after stimulation of receptors in the nose have been studied in the anaesthetized dog.2. Stimulation of a carotid body by infusion of cyanide into the ipsi-lateral common carotid artery causes hyperpnoea and either an increase, decrease or no change in pulse interval.3. Excitation of receptors in the nasal mucosa leads to reflex apnoea or a reduction in breathing, and an increase in pulse interval.4. When the carotid bodies are excited by the same dose of cyanide during stimulation of the nasal mucosa, the chemoreceptor-respiratory response is abolished or reduced in size compared with the control effect. On the other hand, the chemoreceptor-cardio-inhibitory response is considerably enhanced.5. The potentiated cardio-inhibitory response of combined chemoreceptor and nasal stimulation could not be accounted for by the change in pulmonary ventilation, arterial P(O2) or P(CO2), or mean arterial blood pressure.6. These results indicate that excitation of the nasal reflex inhibits the chemoreceptor-respiratory reflex response but facilitates the chemoreceptor-cardio-inhibitory reflex response. The possible sites of these interactions between the nasal and chemoreceptor reflexes are discussed.     

Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs.

Interactions among vascular reflexes evoked from carotid sinuses, carotid bodies, and cardiopulmonary region were examined in anesthetized, atropinized, and respired dogs with aortic nerves cut. The carotid sinuses were perfused at 220, 150, and 40-50 mmHg; the chemoreceptors were stimulated by perfusion with hypoxic hypercapnic blood. Cardiopulmonary vasomotor inhibition was interrupted by vagal cold block. Measurements were made of arterial blood pressure and of kidney and hindlimb vascular resistance. At sinus pressures less than 170-160 mmHg, cardiopulmonary vasomotor inhibition increased with increase in blood volume. At high sinus pressure, interruption of this augmented cardiopulmonary inhibition was as ineffective in changing vascular resistance as interruption of the lesser inhibition present during normovolemia. Chemoreceptor stimulation increased the response to vagal block at intermediate but not at high or low sinus pressure. The studies demonstrate the dominant role of the carotid sinus reflex when the three systems interact and the ineffectiveness of chemoreceptor stimulation when carotid or cardiopulmonary inhibition is maximal.     

Cardiovascular-respiratory reflex interactions between carotid bodies and upper-airways receptors in the monkey.

The carotid bodies were stimulated in the anesthetized pig-tailed macaque monkey (Macaca nemestrina) using i) brief injections of cyanide or CO2-equilibrated bicarbonate solution into a common carotid artery, and ii) longer perfusion with hypoxic hypercapnic blood in vascularly isolated chemoreceptor preparations. In spontaneously breathing animals, brief stimulations of the chemoreceptors consistently caused an increase in pulmonary ventilation, bradycardia, and an increase in femoral vascular resistance. When the same chemoreceptor stimulus was superimposed during the apneic period, reflexly evoked by stimulating either the central ends of the superior laryngeal nerves or the nasopharynx, the respiratory stimulation was absent or minimal, but the bradycardia and vasconstriction were greatly enhanced and exceeded the summed responses of separate stimulation of the chemoreceptors and one or the other of the upper-airways inputs. With sustained stimulation of the carotid bodies, hyperventilation, tachycardia, and femoral vasodilatation occurred due to overriding respiratory mechanisms. When superior laryngeal nerve stimulation was superimposed on this response, apnea occurred and tachycardia was reversed to bradycardia, and femoral vascular resistance increased above resting level. The interaction of autonomic responses resulting from chemoreceptor stimulation and from increases in the upper-airways inputs are qualitatively similar in the monkey and in subprimate species. Those involving specifically cardioinhibitory vagal responses are, in part at least, dependent on mechanisms related to the concomitant changes in respiration.     

Vasomotor responses in the hind limbs of foetal and new-born lambs to asphyxia and aortic chemoreceptor stimulation

1. Hind limb blood flow was measured in lambs of from 91 days gestation (delivered by Caesarean section) to 1 month after birth (term is about 147 days), under chloralose anaesthesia. Vascular resistance/100 g wet wt. increased progressively with age. There was reflex femoral vascular tone from the earliest age studied, as shown by vasodilatation on cutting the sciatic nerve.

2. On asphyxia by cord occlusion reflex femoral vasoconstriction began earlier and was somewhat greater in older foetal lambs. At all ages, and after denervation of the hind limb, there was vasodilatation after local ischaemia, and a vasoconstriction of delayed onset during asphyxia attributed to release of noradrenaline into the circulation. The vasoconstrictor effect of noradrenaline in immature lambs was at least as great as at term or in the new-born.

3. Injections of minimal effective doses of cyanide were used to localize possible chemoreceptor sites in foetal lambs. Injection into the left atrium caused a rise of arterial pressure, femoral vasoconstriction and a complex change in heart rate (usually bradycardia) but rarely any respiratory movement. After atropine, cyanide caused a large tachycardia. All responses were much reduced or abolished by cervical vagotomy.

4. Injection of the same doses of cyanide into a jugular vein, the right ventricle, pulmonary or common carotid arteries of foetal lambs caused negligible cardiovascular or respiratory effects, whereas injection into the carotids of new-born lambs caused a profound hyperpnoea.

5. It is concluded that the aortic chemoreceptors are active in the foetus, are supplied from the left heart, and that they probably represent the primary defence in blood gas homeostasis by their effects on the circulation.

     

Carviobascular alterations associated with bursts of panting in the exercising dog

1. In conscious dogs exercising on a treadmill variations in arterial blood pressure and heart rate which were correlated with bursts of panting were observed. The blood pressure variations reflected similar variations in the total peripheral vascular resistance.2. During exercise a change in respiration from slow breathing to panting was followed by a systemic vasodilatation and fall in blood pressure, but a rise in heart rate. Analysis of the time course of these effects demonstrated that the heart rate increase occurred later than the blood pressure fall.3. The correlation between panting and blood pressure changes was not abolished by either of the receptor-blocking drugs atropine sulphate or propranolol, nor by either of the following surgical procedures: acute bilateral cervical vagotomy, and denervation of the carotid sinus baroreceptors and carotid body chemoreceptors.4. The vasodilatation which followed a burst of panting appeared to be due to a decrease in adrenergic vasoconstrictor sympathetic nerve activity, and not to a change in the chemical composition of the arterial blood.5. It is concluded that the vascular changes are not reflex responses to stimulation of peripheral receptors by the bursts of panting. Instead, it is suggested that both the bursts of panting and associated falls in blood pressure are parallel effects resulting from activation at a suprabulbar level of the central nervous system. It is also concluded that the variations in heart rate are mediated by the baroreceptor reflex mechanism, activated by the changes in mean blood pressure.     

Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the cat

In mammals there are two sets of peripheral arterial chemoreceptors, the carotid bodies innervated by the sinus branch of the glossopharyngeal nerve and the aortic bodies innervated by the vagus nerves. The afferent impulse discharge from both receptors increases during hypoxia and there is a reflexly mediated increase in ventilation (hypoxic hyperventilation). In the present study we tested this response by exposing anesthetized cats to decreased inspired O₂ concentration before and up to 315 days after bilateral resection of the carotid bodies. Acutely after removing the carotid bodies, hypoxic hyperventilation was abolished. This observation supports the view that the reflex pathway from the aortic body receptors normally contributes minimally to hypoxic hyperventilation. Subsequently, there was a restoration of hypoxic hyperventilation. Restoration was significant 30–43 days after removing the carotid bodies, it reached 70% of the preoperative value at 93–111 days and was essentially complete in terminal experiments 260–315 days after carotid body resection. In terminal experiments, hypoxic hyperventilation was not affected by recutting the regenerated carotid sinus nerves but was abolished completely by bilateral transection of the cervical vagosympathetic trunks. The restored ventilatory response was due predominantly to an increase in rate of breathing while an increase in tidal volume was predominant before carotid body resection. Resting ventilation breathing room air was not consistently decreased after carotid body resection while expired CO₂ was elevated from day 20 to day 111 and at the preoperative level in terminal experiments.It is concluded that restoration of hypoxic hyperventilation in the cat after carotid body resection is mediated by the reflex pathway from aortic body chemoreceptors. The possible contribution of chemo-receptive regenerated carotid sinus nerve axons was excluded. It is suggested that restoration may be a consequence of the central reorganization of chemoreceptor afferent pathways consequent to interruption of the carotid body reflex pathway and that as a result the ‘gain’ of the aortic body ventilatory chemoreflex is enhanced.     

The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels

1. Cerebral blood flow was measured in 17 baboons, anaesthetized with pentobarbitone, paralysed with gallamine and mechanically ventilated and in which the right sinus and both aortic nerves had been cut and the left carotid sinus vascularly isolated. Later in each experiment, the head was artificially perfused with femoral arterial blood via the innominate artery.2. Stimulation of the carotid body chemoreceptors with venous blood invariably caused a rise in regional cerebral blood flow whether the head was naturally or artificially perfused. This response was almost completely abolished if the VIIth cranial nerves were cut intracranially.3. Regional cerebral blood flow varied inversely with carotid sinus pressure.4. After the remaining (left) sinus nerve had been cut, the cerebral vascular response to hypoxia was negligible and the response to hypercapnia was markedly reduced. Blood flow then varied with perfusion pressure.5. These results provide further evidence that cerebral blood vessels are reflexly controlled and that the peripheral arterial receptors are involved. Their action is most conspicuous in the vascular response to hypoxia and together with intrinsic factors in the cerebral vascular bed, they determine the size of the vascular response to changes in CO(2) and pressure.     

An analysis of the reflex systemic vasodilator response elicited by lung inflation in the dog

1. A maintained inflation of the lungs caused a reflex reduction in total systemic vascular resistance in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow and the arterial blood P(O2) and P(CO2) were maintained constant.2. The fall in systemic arterial perfusion pressure evoked by inflation of the lungs was accompanied by an increase in blood flow to the lower limbs and a reduction in their calculated vascular resistance. Since the fall in resistance occurred when the limb was perfused either at constant pressure or at constant blood flow, it must be due to vasodilatation.3. Lung inflation caused vasodilatation in skin, muscle, and in the splanchnic vascular bed. The responses in vertebral circulation were, however, small and variable.4. The vasodilator responses in the vascular territories studied were reflex in nature, being abolished by cutting the cervical vagosympathetic nerves, in which run the afferent fibres, or by interrupting the sympathetic pathways to the blood vessels.5. In the intact limb, muscle, skin and splanchnic vascular bed, the vasodilator responses to lung inflation were unaffected by atropine or propranolol, but were abolished by hexamethonium, dibenyline and bretylium tosylate, indicating that they were due predominantly to a reduction in the activity in sympathetic adrenergic vasoconstrictor fibres.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

Search for pulmonary arterial chemoreceptors in the cat, with a comparison of the blood supply of the aortic bodies in the newborn & adult animal

1. Electrophysiological and histological techniques have been employed to search for pulmonary arterial chemoreceptors in kittens and cats.2. In cats, impulses were recorded from vagal fibres arising from chemoreceptors in the aortico-pulmonary region. The receptors were identified by their response to hypoxia, and their location was investigated by comparing the effects of injecting drugs at various sites in the pulmonary and systemic circulations. In only one of a large number of experiments did a chemoreceptor appear to receive pulmonary rather than systemic arterial blood.3. No chemoreceptor impulses were evoked when a segment of the pulmonary artery was perfused as described by Duke, Green, Heffron & Stubbens (1963).4. The vasculature of the aortico-pulmonary bodies was displayed by micro-dissection following injection of coloured gelatin masses, and the bodies were examined histologically. In the new-born kitten, the pulmonary artery invariably furnished a branch to some aortic bodies but the vessel frequently anastomosed with systemic arteries. As post-natal development proceeded the vessel became occluded, and in most kittens more than a month old and in forty-one of forty-three cats the aortic bodies were supplied wholly by systemic arteries.5. It was concluded that a pulmonary arterial supply to aortic bodies in the adult animal is an uncommon variation owing to the abnormal persistence of a foetal condition.6. Results indicated that the nomenclature introduced by Howe (1956) is, with slight modification, a useful method of classifying the various groups of aortic bodies according to their position, blood supply and innervation.     

Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.     

The effects of hyperventilation on the reflex cardiac response from the carotid bodies in the cat

1. Cats were anaesthetized with chloralose and urethane, and ventilated by an artificial intermittent negative pressure applied to the thorax. The carotid body chemoreceptors were isolated and perfused with oxygenated blood. They were stimulated by substituting hypoxic blood obtained from a donor animal.2. Stimulation of the carotid bodies during constant ventilation caused a bradycardia. When an artificial hyperventilation was induced during carotid body stimulation the heart rate increased.3. The increase in heart rate during hyperventilation, and while the carotid bodies were being stimulated, was due to at least two mechanisms, first a reflex from the lungs and secondly a fall in arterial blood P(CO) (2), both of which accompany the hyperventilation.     

Coronary vascular and myocardial responses to carotid body stimulation in the dog.

Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood.     

Effects of graded pulsatile pressure on the reflex vasomotor responses elicited by changes of mean pressure in the perfused carotid sinus-aortic arch regions of the dog

1. In the anaesthetized dog, the carotid sinuses and aortic arch were isolated from the circulation and separately perfused with blood by a method which enabled the mean pressure, pulse pressure and pulse frequency to be varied independently in each vasosensory area. The systemic circulation was perfused at constant blood flow by means of a pump and the systemic venous blood was oxygenated by an extracorporeal isolated pump-perfused donor lung preparation.2. We have confirmed our previous observations that under steadystate conditions the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in carotid sinus pulse pressure, whereas those evoked by changes of mean aortic arch pressure are only weakly affected by modifications of aortic pulse pressure.3. When the carotid sinus and aortic arch regions are perfused in combination at constant pulse frequency (110 c/min), the relationship between mean carotid sinus-aortic arch pressure and systemic arterial perfusion pressure is dependent on the size of the pulse pressure.4. Increasing the pulse pressure alters the curve relating the mean carotid sinus-aortic arch pressure to systemic arterial perfusion pressure in such a way that the perfusion pressure is lower at a given carotid sinus-aortic arch pressure within the range 80-150 mm Hg. The larger the pulse pressure, up to about 60 mm Hg, the greater the fall in systemic arterial perfusion pressure. Above a mean carotid sinus-aortic arch pressure of about 150 mm Hg, alterations of pulse pressure have little effect.5. There is a family of curves representing the relation between mean carotid sinus-aortic arch pressure and systemic vascular resistance, depending on the pulse pressure.     

The mechanism of action of carbon dioxide on the limb vessels of the cat

Summary A study was made of the reflex and direct action of the arterial blood CO₂ surplus on the vascular tone of the posterior extremity in a cat perfused with donor's blood by means of a pump, providing a constant blood inflow. During inhalation of the air mixture containing 7–10% CO₂ by the recipient vascular constriction was noted in the perfused extremity. When inhaled the same mixture is inhaled by the donor (direct action) the constriction effect is also observed. Following denervation of the extremity, the same mixture inhaled by the donor caused vascular dilatation.It is suggested that the direct vasoconstricting effect of the CO₂ blood surplus is not manifested in the extremity because of the prevalence of the vasoconstricting reflex effect from the chemoreceptors of the carotid bodies and the aorta arc as well as from the receptors of the extremity itself.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 53, No. 4, pp. 12–15, April, 1962