The subclavian artery as the first branch of the aortic arch.
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Biomedical subjects
Publications and source records attributed to J W Duckworth.
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Changes in cortical blood flow and cerebrovascular activity occurring during and after cortical spreading depression (CSD) were studied in alpha-chloralose-urethan-anesthetized cats. CSD was induced by superficial cortical pinprick, and laser-Doppler velocimetry (LDV) was used to measure cerebral blood flow (CBFLD). CSD resulted in a wave of cortical hyperemia during which there was a 215 +/- 48% peak increase in cortical blood flow that lasted for 2.7 +/- 0.4 min. This hyperemic phase was followed by prolonged cortical oligemia, with a reduction in flow of 20 +/- 4% at 1 h and 28 +/- 4% at 2 h. After CSD, cerebrovascular reactivity to the inhalation of CO2 was abolished and did not fully recover for at least 10 h. Spontaneous vasomotor activity in the cerebral microcirculation was significantly decreased after CSD, and autoregulation of cortical blood flow in response to hypotension was preserved. The abnormal cerebrovascular reactivity seen after CSD in the gyrencephalic cortex of the cat has possible significance for human migraine with aura.
Regional cerebral blood flow (RCBF) was studied during low frequency (15/s) and high frequency (50/s) electrical stimulation of the locus coeruleus (LC) in the alpha-chloralose-anesthetized cat using the freely diffusible tracer [14C]iodoantipyrine and regional brain dissection. The responses were determined in animals spinalized at the C1/C2 level to eliminate systemic effects of pontine stimulation such as alterations in blood pressure and heart rate. The spinalization, itself, did not alter resting RCBF or reactivity to hypercapnia. Low frequency stimulation reduced regional cerebral blood flow in the cortex, basal ganglia and white matter of the corpus callosum. The reductions in RCBF were maximal (35%) in the occipital cortex whereas no changes were seen in the colliculi. No changes were seen in any brain areas with high frequency stimulation. The relevance of this brainstem effect on cerebral blood flow to pathological states such as stroke and migraine is discussed.
The responses of cerebral arteries to catecholamines and sympathetic nerve stimulation show wide variation between animal species. We examined the catecholaminergic histofluorescence and the contractile responses elicited by transmural electrical field stimulation and norepinephrine (NE) in proximal segments of human middle cerebral artery (MCA) obtained during autopsy. Twenty-four percent of the specimens were obtained within 2 hours and 76% within 4 hours of death. A moderately dense catecholaminergic histofluorescence was seen in all segments of human MCA using the glyoxylic acid technique, counterstained with pontamine sky blue. However, only seven of 35 (20%) MCA segments tested showed tetrodotoxin-blocked transmural electrical field stimulation contractions, and all of these were harvested within 4 hours of death. The responses were mostly seen in the most proximal MCA segments and, at 32 Hz, only achieved 6 +/- 1% of the maximal tissue contraction. NE caused two distinct responses in human MCA segments. At low concentrations, it acts via an alpha-like adrenoreceptor to cause contractions 20 +/- 3% of the maximal tissue response. The NE ED50s for the three successive segments were not different from each other; the value for the most-proximal segment was 7.9 +/- 0.2 x 10(-7) M. At concentrations above 10(-5) M, this catecholamine acts on low-affinity sites resistant to alpha-adrenergic antagonists causing contractions that at 10(-3) M reach 52 +/- 5% of the maximal tissue response.(ABSTRACT TRUNCATED AT 250 WORDS)
The superior sagittal sinus (SSS) and the trigeminal ganglion (Vg) of anesthetized cats were stimulated electrically and field potentials in the upper cervical spinal cord and regional cerebral blood flow were recorded. Stimulation of the entire ganglion produced smaller field potential changes in two regions (medioventral area (MVA); dorsolateral area (DLA] of the upper spinal cord than did stimulation of the sagittal sinus (Vg/SSS response ratio = 17% for the MVA and 48% for the DLA). Stimulation of the trigeminal ganglion increased blood flow in only the frontal and parietal cortices (+93% and +33%), whereas stimulation of the sinus produced both larger changes in these areas (+137% and +139%) and also produced changes in regional cerebral blood flow in the thalamus (+122%).
Regional cerebral blood flow was studied in the cat, with and without trigeminal ganglion stimulation, by the intravenous injection of the tracer [14C]iodoantipyrine and subsequent regional brain dissection. Electrical activation of the trigeminal ganglion led to a selective increase in regional blood flow in the frontal and parietal cortex that was bilateral without change in the posterior cortex, deep cerebral nuclei, white matter, or brain stem. Unilateral intracranial section of the facial nerve blocked the response in the ipsilateral frontal and parietal cortex, whereas bilateral facial nerve section blocked the contralateral frontal cortical response. The contralateral parietal cortical increase in blood flow was not affected by facial nerve section and may thus represent the result of metabolic activation of sensory cortex.
We have examined the responsiveness of the vertebro-basilar circulation of the anesthetized Macaca nemestrina monkey to vasoactive agents infused directly into the artery. Infusion of noradrenaline caused a slight increase in vertebral arterial resistance. This constriction was less than that seen in previous experiments with either the internal or vertebral arterial resistance. This constriction was less than that seen in previous experiments with either the internal or external carotid arteries. In the presence of vasodilatation caused by inhalation of a CO2-rich gas mixture, this constriction became a dilatation. Serotonin was without significant effect on the vertebral arterial bed. Bradykinin, histamine and prostaglandin E1 all produced slight dilatation, with bradykinin being the most potent. In all cases the concentration required to produce an effect on the vasculature was much greater in the vertebral circulation than it is in the internal carotid and extracerebral circulations. We conclude that the intact vertebro-basilar circulation is much less sensitive to vasoactive agents than experiments with isolated segments of these arteries would indicate and that therefore these agents are unlikely to play a significant part in the pathogenesis of vertebro-basilar migraine.
Stimulation of the trigeminal nerve or ganglion in the cat caused a frequency-dependent reduction in carotid vascular resistance. Systemic arterial blood pressure (SABP) decreased at low frequencies (0.2 to 5 sec-1) and increased at higher frequencies, thus increasing carotid blood flow at the higher frequencies. The effect on resistance was predominantly ipsilateral and was unaltered by cervical sympathectomy, but was abolished or substantially reduced by section of the trigeminal root proximal to the ganglion. Diminution of carotid vascular resistance was replicated by stimulation of the greater superficial petrosal (GSP) nerve without any change in SABP. Section of the seventh cranial nerve reduced or abolished the response to stimulation of the trigeminal nerve but not that from the GSP nerve. The trigeminal response was prevented by ganglion-blocking drugs in seven out of eight cats. The resistance response was unaffected by noradrenergic, cholinergic, serotonergic, and histamine-2 blocking agents. No neural connection could be demonstrated between the GSP and the trigeminal ganglion, and the vascular response to GSP stimulation persisted after trigeminal section. It is concluded that activation of the trigeminal system increases carotid blood flow by a pathway involving the seventh cranial nerve, the GSP and Vidian nerves, and a parasympathetic synapse employing an unconventional transmitter. A varying proportion of the response (greatest in the third division) may be mediated by antidromic activation of trigeminal nerves. These findings may have clinical implications for the vascular changes of migraine and other facial pain.
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Migraine therapy using low doses of clonidine has been based on the proposal that clonidine directly inhibits vascular smooth muscle reactivity. In anaesthetized monkeys in which internal and external carotid vascular resistances were measured, the only significant effects of clonidine administered acutely (0.5 and 2 microgram x kg-1 i.v.) or chronically (2 microgram x kg-1 i.m. daily for 7 days) on cranial vascular responses to the constrictors noradrenaline and 5-hydroxytryptamine, and the dilators histamine, prostaglandin E1 and bradykinin, were small potentiations of some of the responses. Acute clonidine initially increased blood pressure and constricted the cranial vasculature, then induced hypotension without involvement of the cranial circulation. It also decreased the external carotid vasoconstrictor response to low frequency cervical sympathetic nerve stimulation. The low chronic dose of clonidine had no hypotensive effect. The pressor response to common carotid occlusion was inhibited by both acute and chronic clonidine. These experiments thus provide no evidence that clonidine inhibits cranial vascular reactivity at doses equivalent to those used in migraine.
In a histological study of 28 human foetal thyroids, ultimobranchial body cysts were found in seven foetuses. Large oval cells were seen adjacent to or within the cysts. There is a morphological resemblance between the cells associated with the ultimobranchial cysts and those of medullary carcinoma of the thyroid gland. This similarity, in humans, substantiates the hypothesis that medullary carcinoma arises from the parafollicular cells, which themselves are known to differentiate from ultimobranchial body tissue.
In a series of 21 human fetal thyroid glands examined histologically in serial sections, seven ultimobranchial body cysts were found. The position of these cysts correlated well with the distribution of calcitonin-containing cells found by previous investigators in the adult thyroid gland. Ultimobranchial body cysts found external to the thyroid lobes may offer a developmental explanation for the paucity of calcitonin found in some adult thyroid glands. The close developmental relationship between the parathyroid gland and the ultimobranchial body could explain the presence of calcitonin found in these glands in some adults.
We have presented the unique clinical and morphological features of 3 patients with an imperforate tricuspid valve and right ventricular tensor apparatus. Thus, despite valve tissue and apparatus, there was not a perforate atrioventricular connection. This most uncommon type of tricuspid atresia' was associated in all 3 cases with a congenitally absent pulmonary valve, an underdeveloped right ventricle, and a curious distortion of the ventricular septum. Indeed, 2 of these patients demonstrated severe disproportionate ventricular septal thickening, although histopathologic examination did not substantiate those features usually associated with a hypertrophic cardiomyopathy. Rather, microscopic examination revealed a sinusoidal malformation consisting of normal myocardial cells separated by branching ethothelial-lined channels which communicated with the right ventricular cavity. In addition, gross examination of these 3 specimens revealed an abnormally persistent right venous valve in 2, which subdivided the right atrium. Finally, these cases provide further evidence that the term 'tricuspid atresia' oversimplifies the observed morphological features.
Internal and external carotid vascular resistances were measured, in anaesthetized monkeys, to asses the direct cranial vascular effects of i.v. methysergide, pizotifen and ergotamine, and their effects on the cranial vascular responses to the constrictors 5-hydroxytryptamine and noradrenaline and the dilators histamine, prostaglandin E1 and bradykinin. Methysergide reduced responses to 5-HT, and tended to potentiate the external carotid responses to noradrenaline. Pizotifen blocked responses to histamine; it tended to reduce internal carotid responses to 5-HT, but it potentiated external carotid 5-HT responses. Ergotamine reduced responses to 5-HT and noradrenaline, but this was probably related to its cranial vasoconstrictor effects, especially in the external carotid circulation. Methysergide induced weak transient cranial vasoconstriction and pizotifen had no direct effects. These findings may be relevant to the therapeutic actions of these drugs in migraine, since the doses used approximated to those used clinically.
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Internal and external carotid blood flows in anesthetized monkeys were measured simultaneously using electromagnetic flowmeters. Complete dose-response relationships were established for the effects of intracarotid infusion of several humoral agents implicated in migraine. Both the internal and external carotid vasculatures were constricted by serotonin and prostaglandin F2alpha and dilated by bradykinin, histamine, and acetylcholine. Noradrenalin and adrenaline constricted the external carotid vasculature but had little direct effect in the internal carotid territory. Prostaglandin E1 dilated the external carotid vasculature. Low doses of prostaglandin E1 produced dilation in the internal carotid circulation, but with higher doses there was a paradoxical abolition of this effect.
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