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Biomedical subjects

M de Burgh Daly

Publications and source records attributed to M de Burgh Daly.

At least 19 recordsLinked to original sources

Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats.

It has been demonstrated previously that the vagal bradycardia evoked by activation of pulmonary C-fibres is not respiratory modulated. Experiments were carried out in alpha-chloralose anaesthetized cats to determine if these cardiac vagal preganglionic neurones (CVPNs) in the nucleus ambiguus (NA), which have respiratory modulated activity, can be activated when pulmonary C-fibre afferents are stimulated by right atrial injections of phenylbiguanide (PBG). Eleven CVPNs with B-fibre axons in the right cardiac vagal branches were identified and found to be localized within or ventrolateral to the nucleus ambiguus. Ionophoretic application of a high current of dl-homocysteic acid (DLH) induced a vagally mediated bradycardia and hypotension in six of eight sites from which CVPNs were recorded. The activity of B-fibre CVPNs, whether spontaneous (n = 4) or induced by ionophoresis of DLH (n = 7) was respiratory modulated, firing perferentially during post-inspiration and stage 2 expiration. This activity also correlated with the rising phase of the arterial blood pressure wave consistent with these CVPNs receiving an arterial baroreceptor input. Right atrial injections of PBG excited nine of eleven CVPNs tested. In eight of these activated neurones the onset latency of the excitation was within the pulmonary circulation time, consistent with being activated only by pulmonary C-fibre afferents. In two neurones the PBG-evoked excitation still occurred when central inspiratory drive was inhibited, as indicated by the disappearance of phrenic nerve activity. In conclusion, B-fibre respiratory modulated CVPNs can be activated following stimulation of pulmonary C-fibre afferents.

Action Potentials↗

Cardiovascular responses to carotid chemoreceptor stimulation in the dog: their modulation by urinary bladder distension.

Respiratory, heart rate and hindlimb vascular responses were studied in response to increasing levels of stimulation of the carotid body chemoreceptors, together with an examination of the modulation of their effects by distension of the urinary bladder in the dog anaesthetized with a mixture of chloralose and urethane. The vascularly isolated carotid bifurcation regions were perfused with blood, stimulation of the carotid bodies being carried out by three different levels of hypoxic isocapnic blood (PO2 approximately 58, 40 and 22 mmHg) obtained from a donor animal. A vascularly isolated hindlimb was autoperfused at constant blood flow through its femoral artery. In spontaneously breathing animals, increasingly intense hypoxic stimulation of the carotid bodies caused a progressive augmentation of respiratory minute volume. Superimposition of distension of the bladder increased ventilation further, by the same amount during hypoxic as during normoxic blood perfusion of the chemoreceptors. Prevention of the effects of lung stretch afferent stimulation by artificial ventilation modified the heart rate and hindlimb vascular responses to excitation of the carotid bodies by revealing or accentuating the primary cardiovascular responses, bradycardia and vasoconstriction. In contrast, no such respiratory modulation was apparent in the cardiovascular responses to bladder distension. When, under conditions of artificial ventilation and in the absence of changes in the arterial baroreceptor input, the primary cardio-inhibitory and vasoconstrictor responses to carotid chemoreceptor stimulation predominated, the heart slowed progressively as the stimulus was increased. At the same time the cardio-accelerator effects of bladder distension progressively diminished, indicating an interaction between the cardiac reflex responses evoked by the two inputs. In contrast, the reflex vascular responses resulting from stimulation of the two inputs were additive, at least for PO2 levels of carotid body perfusate down to approximately 40 mmHg. In conclusion these experiments demonstrate the differential nature of the integration of respiratory and cardiovascular responses evoked by stimulation of the carotid chemoreceptors and bladder distension.

Animals↗

Trigeminal and carotid body inputs controlling vascular resistance in muscle during post-contraction hyperaemia in cats.

1. In anaesthetized cats, the effects of stimulation of the receptors in the nasal mucosa and carotid body chemoreceptors on vascular resistance in hindlimb skeletal muscle were studied to see whether the responses were the same in active as in resting muscle. The measurements of vascular resistance were taken, first, in resting muscle, and second, in the immediate post-contraction hyperaemic phase that followed a 30 s period of isometric contractions. 2. Stimulation of the receptors in the nasal mucosa caused reflex apnoea and vasoconstriction in muscle. The latter response was attenuated when the test was repeated during post-contraction hyperaemia. 3. Stimulations of the carotid bodies were made during a period of apnoea evoked reflexly by electrical stimulation of both superior laryngeal nerves. This apnoea prevented any effects of changes in respiration on the carotid body reflex vascular responses. Stimulation of the carotid bodies evoked hindlimb muscle vasoconstriction. In the post-contraction hyperaemic period, the response was reduced or abolished. A similar attenuation of the reflex vasoconstrictor responses occurred in decentralized muscles stimulated through their motor roots in the cauda equina. 4. Evidence is presented that the attenuation of the vasoconstrictor responses evoked by the two reflexes is a phenomenon localized to the contracting muscles themselves resulting from an interaction between sympathetic neuronal activity and the local production of metabolites. 5. The results are discussed in relation to the metabolic needs of tissues in relation to asphyxial defence mechanisms such as occur in the diving response.

Animals↗

Reflex cardiac dromotropic responses to stimulation of the carotid and aortic chemoreceptors in the anaesthetized cat.

1. The reflex changes in the dromotropic state of the heart (P-R interval or atrioventricular conduction time) in response to selective stimulation of the carotid and aortic bodies by sodium cyanide were studied in the anaesthetized cat. The heart was paced and the arterial blood pressure was kept constant to minimize secondary effects of changes in arterial baroreceptor activity. 2. Stimulation of the carotid and aortic bodies caused an increase in the atrioventricular conduction time. 3. Evidence is presented to suggest that this negative dromotropic response was due predominantly to a vagal cholinergic mechanism. There is a small sympathetic component but only in so far as the carotid body reflex is concerned. 4. The negative dromotropic responses were enhanced during reflex suppression of the central inspiratory neuronal drive combined with minimal activity of the slowly adapting pulmonary stretch afferents indicating that they are respiratory modulated. 5. The clinical implications of these results are discussed.

Analysis of Variance↗

Effects of distension of the urinary bladder on the cardiovascular reflexes from the carotid baroreceptors in the dog.

1. The hindlimb vasoconstrictor effects of distension of the urinary bladder were studied at different levels of input from the carotid sinus baroreceptors in the dog anaesthetized with a mixture of chloralose and urethane. 2. The vascularly isolated hindlimb was perfused at constant blood flow through its femoral artery, so that a change in pressure gradient (mean femoral arterial perfusion pressure minus mean inferior vena caval pressure) indicated a similar directional change in vascular resistance. The vascularly isolated carotid sinus regions were perfused with blood at a constant pulsatile flow. 3. Raising the carotid sinus mean perfusion pressure in randomly selected steps of 30 mmHg from 60 to 210 mmHg had little effect on heart rate unless the blood pressure was controlled, when a progressive bradycardia occurred, but caused a progressive reduction in arterial blood pressure and vasodilatation in the perfused hindlimb. Distension of the bladder at each level of carotid sinus pressure resulted in tachycardia, hypertension and hindlimb vasoconstriction. 4. The cardiac responses to bladder distension were the same at all carotid sinus pressures. When the blood pressure was controlled, however, the response was reduced at high and low sinus pressures. 5. The relationship between the carotid sinus perfusion pressure and hindlimb perfusion pressure (i.e. vascular resistance) was affected by distension of the bladder in two ways. In the one, hindlimb perfusion pressure increased by approximately the same amount at all levels of carotid sinus pressure indicating resetting of the carotid sinus baroreceptor reflex control of hindlimb vascular resistance towards vasoconstriction without change in gain of the reflex. In the other, the pressure increases were diminished at the higher levels of carotid sinus pressure indicating both resetting and an increase in gain of the reflex. 6. Both types of response occurred in the spontaneously breathing animal, in animals artificially ventilated, while pacing the heart, with the arterial blood pressure maintained constant at about 100 mmHg, and after division of the cervical vagosympathetic nerves. The frequency of occurrence of each type of response, however, varied under the different conditions. 7. The possible reasons for the two types of vascular response are discussed.

Animals↗

A morphological study of the size of the vascular compartment of the carotid body in a non-human primate (Cercopithecus ethiopus), and a comparison with the cat and rat.

The carotid bodies from 5 adult non-human primates (mean body weight 2.9 kg) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde. Serial 5-microns sections were cut, stained, and, using an interactive image analysis system, determinations were made of the volumes of the carotid body and of its vascular and extravascular compartments. The total volume of the carotid body was, on average 0.21 mm3, the total vascular volume contributing 9.7%. The small vessels (5-12 microns diameter) comprised 5.4% of the total volume of the carotid body, or about 56% of the vascular compartment; these estimates were similar to values obtained for the cat and rat. The mean small vessel endothelial area, per unit of extravascular volume (which is assumed to consist largely of type 1 and 2 cells) was 61.8 mm-1 in the primate and 69.7 mm-1 in the cat. A value was not available for the rat. Estimates of the carotid body tissue specific blood flow were 31, 61 and 104 ml/min/100 g organ tissue in the primate, cat and rat, respectively. It was emphasised that these values were not to be confused with estimates of carotid body specific blood flow based on values for total organ blood flow and the dissected weight of the organ.

Animals↗

Comparison of the size of the vascular compartment of the carotid body of the fetal, neonatal and adult cat.

The carotid bodies from full-term fetal cats, 3- to 4-day-old neonates and adult cats were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde. Serial 5-microns sections were cut and stained by the MSB method. Using an interactive image analysis system, determinations were made of the volumes of the carotid body and of its vascular and extravascular compartments. Compared to the fetus, the carotid body of the neonate increased in volume by 51% and by 286% in the adult cat. There was a proportional increase in the volumes of the vascular compartment and of the small vessels (5-12 microns diameter) in that compartment. The volume of the small vessels, expressed as a ratio of the total volume of the organ, remained constant in the three animal groups at 5-7%. The small vessel endothelial surface area, expressed as a ratio of the extravascular volume (which was assumed to consist largely of type 1 and type 2 cells), was the same in the neonate as in the full-term fetus. Thus, there were no apparent quantifiable morphological features of the carotid body and its vasculature which would account for the resetting of the hypoxic sensitivity of the organ from the fetal to the adult range within a few days of birth.

Aging↗

The carotid body of the mini-pig.

The bilateral distribution of carotid body type 1 and 11 cells was investigated in 3 mini-pigs by serially sectioning the carotid bifurcation regions. The majority of type 1 and 11 cells occurred bilaterally in close proximity to the wall of the occipital artery or one of its small proximal branches, the internal carotid artery and the common arterial trunk. A division of connective tissue surrounded the type 1 and 11 cells with defineable but very irregular borders and this combination of connective tissue and cells constituted the principal mass of the carotid body. In the majority of specimens the cells were diffusely arranged giving a fragmented appearance to the organ but in 2 specimens part of the carotid body was discrete, adopting an ovoid or crescent-shaped appearance over a limited rostral-caudal part of its extent. Arteries to the carotid body originated from the occipital arterial tree in the vicinity of the division of the common arterial trunk and less commonly from the common arterial trunk itself. A supplementary blood supply came from unidentified connective tissue arterioles. In 2 out of 6 specimens type 1 and 11 cells were associated with cervical nerve trunks. Periadvential type 1 and 11 cells were observed in one out of 6 specimens lying dorsal to the common arterial trunk. From our data on 6 specimens, three dimensional reconstructions were made of ventral views of the distribution of carotid body type 1 and 11 cells. On account of the diffuse arrangement of the mini-pig carotid body, morphometric analysis of the organ volume was not feasible.

Animals↗

Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia.

We tested the following hypothesis: if carotid body blood flow, and hence the relationship of the frequency of discharge in chemoreceptor afferent fibres to arterial PO2, were affected by atherosclerotic change, then a modification of the control of the respiratory and cardiovascular systems might result. Carotid body reflexes were therefore studied in conscious atherosclerotic rabbits and a control group of normal animals breathing 100% O2, three hypoxic gas mixtures to which was added sufficient CO2 to maintain the arterial PCO2 constant, and 2% and 4% CO2 in 21% O2 and N2. When breathing room air, the atherosclerotic rabbits breathed at a higher respiratory frequency and lower tidal volume than the normal animals, although there was no difference in the respiratory minute volume. The respiratory and cardiovascular responses to hyperoxia, isocapnic hypoxia and hypercapnia were essentially the same in both groups of animals. Serial sections of the carotid bodies showed pathological changes including interstitial fibrosis in the caudal part with interstitial haemorrhages. The proximal part of the ascending pharyngeal artery, the vessel supplying the organ, and its origin from the external carotid, and the arterioles in the caudal part of the carotid body were nearly always occluded to a varying extent by atheromatous plaques. The capillaries appeared normal under light microscopy. The rostral-caudal lengths of the carotid bodies were similar in the two groups. We conclude that the peripheral arterial chemoreceptor responses in atherosclerotic rabbits are relatively normal even though the arteries to, and arterioles within, the carotid body are partly occluded.

Animals↗

Cardiovascular responses to stimulation of cardiac receptors in the cat and their modification by changes in respiration.

1. In cats anaesthetized with a mixture of chloralose and urethane, stimulation of cardiac receptors by left atrial injections of veratridine had little or no effect on pulmonary ventilation but caused bradycardia, systemic hypotension and hindlimb vasodilation with a latency of 3.3 s. 2. The hindlimb vasodilatation was due largely, if not entirely, to a reduction in sympathetic vasoconstrictor activity. 3. Similar cardiovascular responses occurred when the arterial blood pressure was maintained constant and also in artificially ventilated animals. 4. When the cardiac receptors were excited during a period of apnoea which was induced reflexly by electrical stimulation of the central cut end of a superior laryngeal nerve, the cardio-inhibitory response to left atrial injections of veratridine was enhanced but the size of the vasodilator response was unaffected. 5. In contrast, the cardiovascular effects of stimulation of the carotid body chemoreceptors, bradycardia and hindlimb vasoconstriction were enhanced by the laryngeal input. 6. The possible central mechanism responsible for the differential modulation of cardiac receptor and carotid chemoreceptor reflexes by respiration are discussed.

Animals↗

The volume of the carotid body and periadventitial type 1 and type 2 cells in the carotid bifurcation regions of the pregnant and lactating cat.

The bilateral distribution of carotid body type 1 cells was investigated in 2 pregnant cats at 95% full term and two lactating cats (2 and 4 d after parturition). Carotid body type 1 and 2 cells occurred bilaterally in close proximity to the occipital artery or one of its branches in a division of connective tissue with defineable but irregular borders. This combination of connective tissue and type 1 and 2 cells constituted the principal mass of the carotid body, which received its blood from the occipital and/or the ascending pharyngeal arteries. Using an interactive image analysis system, the area of the carotid body in each serial section was measured by accurately contouring its perimeter. The volume of the carotid body was calculated by multiplying the sum of the contoured areas of the serial sections by the thickness of the section. The volumes for the carotid bodies in pregnant cats ranged between 0.186 and 0.278 mm3 while the values in lactating animals lay between 0.287 and 0.356 mm3. Caudally and separate from the carotid body, isolated groups of periadventitial type 1 and 2 cells were found in 5 out of 8 specimens around the occipitoascending pharyngeal trunk, origin of the occipital artery, external carotid artery and rostral part of the common carotid artery. The volumes of the periadventitial type 1 and 2 cells were variable in pregnant and lactating cats.

Animals↗

The carotid body of the harbour seal (Phoca vitulina richardsi).

The bilateral distribution of carotid body type 1 and 11 cells was investigated in five harbour seals (Phoca vitulina richardsi), by serially sectioning the carotid bifurcation regions. The cells occurred bilaterally in the animals and were also present in one specimen from a sixth animal available for study. The type 1 and 11 cells were located in the space between the internal and external carotid arteries and had a varied relationship to the occipital and condyloid arteries. They lay within a division of connective tissue with irregular but defineable borders and this combination of connective tissue and type 1 and 11 cells constituted the principal mass of the carotid body. The carotid body occurred in a variety of forms: wedge-shaped, crescentic or horse-shoe shaped, or as a discrete oval structure. In some specimens the carotid body had a central 'neurovascular' core of small blood vessels and nerves. The artery to the organ originated from either the external carotid, internal carotid or common carotid arteries. Using an interactive image analysis system in eight specimens, which had been perfusion-fixed at a normal arterial pressure, the mean volume of the carotid body was 1.666 +/- 0.45 (SD) mm3. Caudally and separate from the principal mass of the carotid body periadventitial type 1 and 11 cells were noted in 4 out of 11 specimens in the connective tissues adjacent to the external carotid artery, origin of the occipital, and the rostral part of the common carotid artery and its bifurcation.

Animals↗

Dimensions and volume of the carotid body in the adult cat, and their relation to the specific blood flow through the organ. A histological and morphometric study.

In perfusion-fixed preparations of the carotid body, morphological measurements were made on serial histological sections using an interactive image analysis system. The volume of the organ was found to be 0.247 +/- 0.092 mm3. This is considerably smaller than the previous estimates based on the measured postmortem wet weight. This means that the specific blood flow to the carotid body of 2,000 ml/min/100 g using the previously obtained values for the organ's total blood flow and postmortem wet weight may be an underestimate of the true value.

Animals↗

Distribution of carotid body type I cells and periadventitial type I cells in the carotid bifurcation regions of the dog.

The bilateral distribution of carotid body type I cells was investigated in 5 mongrel dogs and compared with the arrangement of type I cells in beagles by serially sectioning the carotid bifurcation regions. The distribution of type I cells was not affected by the pedigree of the dogs. In both mongrel dogs and beagles type I cells were arranged in close proximity to the wall of the ascending pharyngeal artery within a division of connective tissue with defineable but irregular borders. Occasionally, type I cells were observed in relation to the occipital and external carotid arteries. This association of type I cells and connective tissue formed the principal mass of the carotid body. Caudally, and separate from the principal mass, isolated groups of periadventitial type I cells lay freely in the connective tissue adjacent to the internal and external carotid arteries in both mongrel dogs and beagles. Less commonly, and in mongrel dogs only periadventitial type I cells were noted alongside the carotid bifurcation and the rostral end of the common carotid artery. Three-dimensional reconstructions of the distribution of carotid body type I cells and periadventitial type I cells from the left and right carotid bifurcation regions were made. In all specimens rostral-caudal dimensions of the distribution of carotid body type I cells and periadventitial type I cells were recorded and compared bilaterally.

Animals↗

A comparative study of the distribution of carotid body type-I cells and periadventitial type-I cells in the carotid bifurcation regions of the rabbit, rat, guinea-pig and mouse.

The bilateral distribution of carotid body type-I cells was investigated in five rabbits, rats, guinea-pigs and mice by serially sectioning the carotid bifurcation regions. Carotid body type-I cells occurred bilaterally in close proximity to the wall of the internal carotid artery in the rabbit, rat and mouse and to the wall of the ascending pharyngeal artery in the guinea-pig. The rat carotid body was sometimes recessed into the lateral aspect of the superior cervical ganglion and was the most easily defined organ in the four animals studied. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type-I cells were observed in the connective tissues around the internal carotid artery and adjacent to the carotid bifurcation and common carotid artery in the rabbits only. An overall picture of the carotid body in the four animals was constructed. In all specimens rostral-caudal dimensions were recorded and compared bilaterally.

Animals↗

Distribution of carotid body type I cells and other periadventitial type I cells in the carotid bifurcation regions of the rabbit.

The distribution of carotid body type I and periadventitial type I cells in the carotid bifurcation regions was investigated unilaterally in seven and bilaterally in two New Zealand White rabbits. Carotid body type I cells occurred in close proximity to the wall of the internal carotid artery immediately rostral to the carotid bifurcation, within a division of connective tissue with definable but irregular borders. Caudally, and separate from the main mass of carotid body type I cells, isolated groups of periadventitial type I cells lay freely in the connective tissue around the internal carotid artery and alongside the carotid bifurcation and common carotid artery. A overall picture of the carotid body in the rabbit was reconstructed and the occurrence and significance of periadventitial type I cells discussed.

Animals↗