An analysis of the inhibition of phrenic motoneurones which occurs on stimulation of some cranial nerve afferents

1. Inhibition and excitation of spontaneous phrenic nerve discharges in response to stimulation of the sinus, glossopharyngeal, aortic and superior laryngeal (SLN) nerves has been investigated in cats.

2. The inhibition, in response to a single shock, had a latency of 5-10 msec and lasted for 20-40 msec; the response to SLN stimulation was the most prolonged.

3. Excitation of phrenic motoneurones also occurred and was seen either before or after the end of the inhibition of the inspiratory burst and sometimes also during expiration.

4. Intravenous strychnine blocked the inhibition.

5. Intracellular recording from phrenic motoneurones showed that hyperpolarization was evoked by each nerve during the central phrenic depolarizing potential (CPDP) but only rarely in the interval between these potentials.

6. When the CPDP was suppressed, hyperpolarization could sometimes be evoked.

7. There were no changes in amplitude or time course of hyperpolarization during the passage of current through the cell membrane. No change in membrane conductance could be shown by passing current pulses.

8. Raising the pressure in the carotid sinus also depressed phrenic activity and evoked a hyperpolarization whilst the CPDP was suppressed.

9. Inspiratory interneurones in the brain stem were suppressed by nerve stimulation and by a rise in carotid sinus pressure.

10. Expiratory interneurones in the brain stem were both excited and suppressed by electrical stimuli and unaffected by a change in carotid sinus pressure.

     

Respiratory responses to occlusion or hypercapnic blood injection of the anterior inferior cerebellar artery in cats

To examine whether the central chemoreceptors of respiration are located in the perfused area of the anterior inferior cerebellar artery (AICA), we occluded arteries or injected hypercapnic blood into arteries in the ventral surface of the medulla in anesthetized, paralyzed, and peripherally chemodenervated cats. Phrenic nerve activity, as an index of respiratory output, was augmented by an injection of hypercapnic blood into the vertebral artery. This vertebral-injection response decreased during bilateral occlusion of AICA. However, responses of phrenic nerve activity to the occlusion of AICA were complicated; activity increased in 19 cats, did not change in 10, and decreased in 9 during occlusion. In experiments with blood of various PCO2 levels being bilaterally injected into AICA, phrenic discharges increased with increases of PCO2. During the injection of constant PCO2 blood into AICA, phrenic response to alveolar PCO2 decreased by 80% compared with the original response. From these results, the blood flow and blood PCO2 level of AICA seemed to be related to the central chemosensitivity for respiration. To examine the perfused area, the ventral surface pH of the medulla was measured with a micro-combination pH electrode (2 mm diameter). During the injection into AICA, pH in the rostral medulla depended on the PCO2 of injected blood, and pH in other areas depended on the PCO2 of systemic blood. Also, histological study of India ink injection into AICA showed that ink-filled vessels were exclusively observed in the rostral medulla. Thus, we conclude that at least part of the central chemoreceptors of respiration are located in the perfused area of AICA, that is, in the rostral medulla.     

Influence of hypercapnia and hypocapnia on bladder contractions and their respiratory consequences

Rhythmic contractions of the detrusor muscle, induced by gradual filling of the urinary bladder in decerebrate or anesthetized cats, are accompanied by decreased inspiratory activity in motor nerves to respiratory muscles, particularly those of the upper airway. We have examined the influence of hypercapnia and hypocapnia on these contractions and the accompanying activities of the phrenic and hypoglossal nerves in decerebrate, vagotomized, paralyzed and ventilated cats, some of which had denervated carotid chemoreceptors. Hypercapnia slowed, and then reversibly abolished bladder contractions in most animals, regardless of the state of the carotid chemoreceptors. Bladder contractions were well maintained in progressive hypocapnia, even at end-tidal CO(2) levels below the 'apneic' thresholds of the hypoglossal and phrenic activities. The reductions of the nerve activities in response to bladder contractions were not significantly altered by hypercapnia or hypocapnia. The abolition of bladder contractions by hypercapnia is unlikely to reflect a direct effect of CO(2) or H+ ion on the contractile mechanism of the detrusor muscle, but may be based on inhibition of stretch receptors in the bladder wall and/or an effect of CO(2) or H+ in or near the micturition centers in the brain stem.     

Responses of simultaneously recorded respiratory-related medullary neurons to stimulation of multiple sensory modalities.

This study addresses the hypothesis that multiple afferent systems share elements of a distributed brain stem network that modulates the respiratory motor pattern. Data were collected from 18 decerebrate, bilaterally vagotomized, paralyzed, artificially ventilated cats. Up to 28 neurons distributed in the rostral and caudal ventral respiratory group, nucleus tractus solitarius, and raphe obscurus were recorded simultaneously with microelectrode arrays. Phases of the respiratory cycle and inspiratory drive were assessed from integrated efferent phrenic nerve activity. Carotid chemoreceptors were stimulated by injection of CO2-saturated saline solution via the external carotid artery. Baroreceptors were stimulated by increased blood pressure secondary to inflation of an embolectomy catheter in the descending aorta. Cutaneous nociceptors were stimulated by pinching a footpad. Four hundred seventy-four neurons were tested for respiratory modulated firing rates and responses; 403 neurons were tested with stimulation of all 3 modalities. Chemoreceptor stimulation and pinch, perturbations that tend to increase respiratory drive, caused similar responses in 52 neurons; 28 responded oppositely. Chemoreceptor and baroreceptor stimulation resulted in similar primary responses in 45 neurons; 48 responded oppositely. Similar responses to baroreceptor stimulation and pinch were recorded for 38 neurons; opposite effects were measured in 26 neurons. Among simultaneously recorded neurons, distinct combinations of firing rate changes were evoked in response to stimulation of the different modalities. The results show a functional convergence of information from carotid chemoreceptors, baroreceptors, and cutaneous nociceptors on respiratory-modulated neurons distributed in the medulla. The data are consistent with the hypothesis that brain stem neurons have overlapping memberships in multifunctional groups that influence the respiratory motor pattern.     

Reflex sympathetic changes in aortic diastolic pressure-diameter relationship.

In anesthetized vagotomized cats with the chest opened and artificially ventilated, aortic blood pressure (AP) and external diameter (AD; ultrasound technique) were measured in the proximal third of the descending thoracic aorta. Slow sinusoidal oscillations (0.2-0.3 Hz in aortic volume were produced by a piston pump connected to a femoral artery. Diastolic pressure-diameter relationship (PDR) curves were obtained during control conditions and during stimulation of either the cut central end of the left inferior cardiac nerve (ICN) or the decentralized thoracic sympathetic chain (SC). In six cats with both carotid arteries occluded ICN stimulation reflexly shifted the PDR curves to lower diameters for any given pressure (mean deltaAD 3.2% at control AP). A smaller response to ICN stimulation was obtained in five cats with one patent carotid artery (mean deltaAD 2.3% at control AP). Stimulation of sympathetic efferents to the aorta (SC) caused similar responses in five animals (mean deltaAD 3.4% at control AP). This reflex control of the thoracic aorta may be involved in cardioaortic coupling and may influence the sensitivity of aortic mechanoreceptors.     

The importance of timing on the respiratory effects of intermittent carotid sinus nerve stimulation

1. The respiratory response, measured directly as tidal volume or indirectly by using integrated peak phrenic activity, to intermittent electrical stimulation of the carotid sinus nerve was determined in anaesthetized cats.2. Stimulation at rates of 20-25 Hz for 0.5 sec had a rapid effect, increasing inspiratory airflow and phrenic discharge, but only if applied during inspiration. An increase in tidal volume or peak level of integrated phrenic discharge occurred only if the stimulus was exhibited during the second half of inspiration. Continuous stimulation had no greater effect on size or frequency of breathing than did intermittent inspiratory stimuli alone. Stimulation during expiration had no effect on the form or magnitude of subsequent breaths.3. Stimuli in expiration led to a prolongation of expiration. Stimuli in late inspiration caused a prolongation of both inspiration and expiration. Because of these effects, the respiratory rate could be changed by stimulation; in some instances entrainment of respiration by the intermittent carotid sinus nerve stimuli occurred.4. The findings are attributable to modulation of incoming carotid sinus nerve information by the central respiratory neurones, which use primarily that which arrives during inspiration. They show a possible mechanism by which oscillating signals may have a different effect than their mean level would indicate.     

Contrasting reflex influences of cardiac afferent nerves during coronary occlusion

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.     

The hemodynamic effect of bilateral carotid artery ligation and the morphometry of the main communicating circuit in normotensive and spontaneously hypertensive rats

After reducing the number of patent conduit arteries to the brain by bilateral ligation of the carotid artery, the percentage decrease in blood pressure from the aorta to the internal carotid artery distal to the ligation was larger in spontaneously hypertensive rats than in normotensive rats. The pressure drop corresponded to the degree of hypertension as well as to morphometrically determined structural arterial alteration in the main communicating circuit, i.e. larger media to internal radius ratio and smaller internal radius in the posterior communicating arteries, the proximal part of the posterior cerebral arteries, the basilar artery and the vertebral arteries. The discrepancy between the sum of the luminal cross sectional areas of the communicating circuit and the luminal areas of the ligated conduit arteries was larger in the hypertensive than in the normotensive rats. It is to be expected that occlusion of conduit arteries to the brain will have a larger impact on the cerebral arterial perfusion pressure head in the presence of such hypertensive structural alterations known to increase flow resistance.     

Mediation of pressor responses to cerebral ischemia by superficial ventral medullary areas

The effects on the pressor response to cerebral ischemia (CIR) of superfusion of the ventral medullary surface with artificial cerebrospinal fluid (CSF) containing local anesthetic was investigated in 10 sinoaortic-denervated, anesthetized cats. Prior to application of the local anesthetic, occlusion of the common carotid and vertebral arteries caused an increase in mean systemic arterial pressure (SAP) of 58 +/- 7 mmHg (+/- SE) from an initial level of 98 +/- 6 mmHg. Following 108 +/- 15 s of superfusion with artificial CSF containing 2% procaine, the CIR decreased to 19 +/- 3 mmHg. At this time phrenic nerve activity had been eliminated but basal SAP had only decreased by 14 +/- 2 mmHg, and significant neurogenic vasomotor tone remained. The residual CIR can be accounted for by the passive increase in systemic resistance due to occlusion of the cerebral vascular bed. The effects of procaine were reversible. On attenuation of the CIR, electrical stimulation of pressor points 2-4 mm from the ventral medullary surface was still effective. Autoradiographic analysis following application of 14C-labeled lidocaine showed that attenuation of the CIR occurred when estimated concentrations of the anesthetic sufficient to block nerve conduction extended 85 micron from the ventral medullary surface. These results indicate that the CIR is mediated by superficial structures in the ventral medulla that are not involved in the generation of a major fraction of basal vasomotor tone.     

A comparative study of middle cerebral pressure in dogs and macaques

1. A comparison has been made of the pressures recorded from pial branches of the middle cerebral artery in dogs and macaques. This pressure has been shown to be between 88 and 95% of femoral arterial pressure in dogs under chloralose anaesthesia, and between 80 and 90% of femoral arterial pressure in macaques similarly anaesthetized.2. The effect of occlusion of the main vessels in the neck is shown to differ considerably in the two species. Blood pressure within the forebrain of the dog is shown to be largely dependent upon the integrity of the external carotid artery, whereas in the monkey the external carotid artery is without effect in the maintenance of forebrain blood pressure. Occlusion of the four major arteries in the neck is shown to produce a greater effect in the macaque and to be accompanied by signs of medullary ischaemia in this species.3. After occlusion of the main middle cerebral artery, arterial pressure measured distal to the occlusion depends upon the integrity of collateral vessels from the other cerebral arteries. When only a branch of the middle cerebral artery is occluded, the greater part of the residual blood pressure depends upon anastomoses from other branches of the middle cerebral artery itself.     

Augmentation of muscle nociceptive respiratory reflex facilitation by vagal afferents

Vagal influence on the facilitation of phrenic neural activity during respiratory phase-locked, gastrocnemius muscle nerve nociceptive electrical stimulation was examined in anesthetized, glomectomized, paralyzed, and artificially ventilated cats. (1) In the vagi-intact state, respiratory reflex facilitation was characterized by a sharp rise in peak amplitude, maximum rate of rise or slope, and mean rate of rise of integrated phrenic nerve activity. This was greater during inspiratory phase-locked (T1-locked) muscle nerve electrical stimulation than during expiratory phase-locked (TE-locked) muscle nerve electrical stimulation. "Evoked post-inspiratory phrenic activity" during the early expiratory phase was also observed during TE-locked muscle nerve electrical stimulation. (2) Bilateral vagotomy significantly attenuated the respiratory facilitation during both T1- and TE-locked muscle nerve electrical stimulation. In particular, the "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation was also attenuated or almost completely abolished. (3) Conditioning electrical stimulation of the vagus nerve revealed facilitatory reflexes which co-exist with inspiratory inhibitory reflexes. (4) The "evoked post-inspiratory phrenic activity" during TE-locked muscle nerve electrical stimulation, which was attenuated or abolished after vagotomy, was restored after vagal T1-locked conditioning stimuli combined with TE-locked muscle nerve electrical stimulation. The results suggest that vagal facilitatory reflexes augment the respiratory reflex facilitation during muscle nociceptive stimulation.     

The Arteries of the Brain in Hare (Lepus europaeus Pallas, 1778)

Research into course and variability of brain arteries in hare were performed on 38 adult hares of both sexes (males 23 and females 15). The arteries were filled with a synthetic latex at a constant pressure introduced with a medical syringe to the left ventricle. The source of blood supply to the brain was internal carotid arteries, whose branches formed an arterial circle of the brain, vertebral arteries, and basilar artery as the result of its anastomosis. Variability focused on a method of departure of middle cerebral arteries, which were multiple vessels in 39.5% of cases and rostral cerebellar arteries. Caudal communicating arteries in hare comprised bilateral anastomosis of internal carotid arteries and final branches of the basilar artery. It stabilized the steady flow of blood to all parts of the brain. Caudal cerebral arteries comprised final branches of the basilar artery. The largest capacity of all the arteries of the brain was observed in the main trunk of the basilar artery. The capacity of these vessels was 4.53 mm³ on average. The factor of capacity of cerebral arteries in relation to weight of the brain reaches a high value in hare. Anat Rec, 298:1774–1779, 2015. © 2015 Wiley Periodicals, Inc.     

Reflex prolongation of stage I of expiration

Experiments were performed on anesthetized cats to test the theory that the interval between phrenic bursts is comprised of two phases, stage I and stage II of expiration. Evidence that these represent two separate neural phases of the central respiratory rhythm was provided by the extent to which stage duration is controlled individually when tested by superior laryngeal, vagus and carotid sinus nerve stimulation. Membrane potential trajectories of bulbar postinspiratory neurons were used to identify the timing of respiratory phases.Stimulation of the superior laryngeal, vagus and carotid sinus nerves during stage I of expiration prolonged the period of depolarization in postinspiratory neurons without significantly changing the durations of either stage II expiratory or inspiratory inhibition, indicating a fairly selective prolongation of the first stage of expiration. Changes in subglottic pressure, insufflation of smoke into the upper airway, application of water to the larynx or rapid inflation of the lungs produced similar effects. Sustained tetanic stimulation of superior laryngeal and vagus nerves arrested the respiratory rhythm in stage I of expiration. Membrane potentials in postinspiratory, inspiratory and expiratory neurons were indicative of a prolonged postinspiratory period. Thus, such an arrhythmia can be described as a postinspiratory apneic state of the central oscillator. The effects of carotid sinus nerve stimulation reversed when the stimulus was applied during stage II expiration. This was accompanied by corresponding changes in the membrane potential trajectories in postinspiratory neurons.The results manifest a ternary central respiratory cycle with two individually controlled phases occurring between inspiratory bursts.     

Influences of lung mechanoreceptors and carotid chemoreceptors on the response of respiratory muscle activity to tracheal occlusion

We examined the responses of respiratory muscle electromyograms (EMGs) from internal (IIC) and external intercostal (EIC) muscles and diaphragm (DIAP) to three successive occluded breaths in anesthetized spontaneously breathing rabbits. Both inspiratory and expiratory muscle EMGs progressively increased in the course of tracheal occlusion. An increase in these muscle EMGs was still observed after release of tracheal occlusion, but those effects were short-lasting. In a separate series of experiments, for assessment of possible reflex effects involved, the responses of slowly adapting pulmonary stretch receptor (SAR), rapidly adapting pulmonary stretch receptor (RAR), and carotid chemoreceptor activities to tracheal occlusion lasting for three respiratory efforts were also examined. The inspiratory discharge of SARs decreased but the expiratory discharge of SARs increased during tracheal occlusion. Although carotid chemoreceptors increased their activity in the latency of 3-6s after the onset of tracheal occlusion, the activity of RARs was greatly reduced throughout the period of tracheal occlusion. A transient increase in both carotid chemoreceptors and RARs was still observed after release of tracheal occlusion. These results suggest that alterations of inspiratory and expiratory muscle EMGs produced by tracheal occlusion would appear to be mediated by the afferent inputs from lung mechanoreceptors and carotid chemoreceptors.     

Repeated inspiratory occlusions acutely impair myocardial function in rats

Repeated episodes of hypoxia and sympathetic activation during obstructive sleep apnoea are implicated in the initiation and progression of cardiovascular diseases, but the acute effects are unknown. We hypothesized that repeated inspiratory occlusions cause acute myocardial dysfunction and injury. In 22 spontaneously breathing pentobarbital-anaesthetized rats, inspiration was occluded for 30 s every 2 min for 3 h. After ∼1.5 h, mean arterial pressure started to fall; heart rate between occlusions was stable throughout, consistent with only transient increases in sympathetic activity during each occlusion. Three hours of occlusions resulted in ventricular diastolic dysfunction (reduced peak rate of change of ventricular pressure and slower relaxation). Post-occlusions, the left ventricular contractile response to dobutamine was blunted. After 1 h of recovery, left ventricular pressure generation had returned to values no different from those in sham animals in 5 of 9 of the animals. Cardiac myofibrils from rats subjected to occlusions had depressed calcium-activated myosin ATPase activity, indicating myofilament contractile dysfunction that was not due to breakdown of contractile proteins. Haematoxylin and eosin-stained cross-sections revealed multifocal areas of necrosis within the septum and both ventricles. Repeated inspiratory occlusions, analogous to moderately severe obstructive sleep apnoea, acutely cause global cardiac dysfunction with multifocal myocardial infarcts.     

Effects of stimulation of phrenic afferent fibers on medullary respiratory neurons in cat

The effects of electrical stimulation of both cervical branches (C5 and C6) of the right phrenic nerve on medullary respiratory neuron activity were studied in anesthetized, spontaneously breathing cats. In 14 cats, the stimulation of the thin phrenic afferents had no effect on the inspiratory duration and evoked excitatory or inhibitory responses in only 3/86 inspiratory neurons tested. In 3 cats, the stimulation decreased the inspiratory duration and 26/26 inspiratory neurons showed a shortened discharge without modification of their discharge frequency. Although the effects of the stimulation were not analysed by averaging techniques, it is concluded that phrenic afferents do not exert an important control on the medullary respiratory neuron discharge.     

Development of AChE-positive, NA-containing and VIP- and NPY-immunoreactive nerves in the major cerebral arteries of the rat

Summary The development of cerebrovascular nerves containing noradrenalin (NA), acetylcholinesterase (AChE), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) was studied in rats from before birth to adulthood. All these nerves entered the cranial cavity along the cerebral carotid, internal ethmoidal, and vertebral arteries during the early stages of development, but the subsequent growth and distribution of NA-containing and NPY-immunoreactive (IR) nerves differed greatly from that of AChE-positive and VIP-IR nerves. NA-containing and NPY-IR nerves extended rapidly from the cerebral carotid artery and spread over all the major arteries of the internal carotid system by postnatal day 3, as well as descending the posterior ramus of the cerebral carotid to mingle with nerves from the vertebral artery around the mid-basilar artery by day 5. AChE-positive and VIP-IR nerves from the internal ethomoidal artery covered the whole internal carotid system during the first postnatal week, and projected to the upper basilar artery after the second week, while those from the cerebral carotid artery remained limited to the middle cerebral artery throughout development. By day 21, all major arteries of the internal carotid system had dense plexuses of the four nerve types that were similar to those observed in adult rats. The vertebrobasilar system also had a well-organized network of NA-containing and NPY-IR nerves, but only a poor supply of AChE-positive and VIP-IR nerves. Even on day 30, the latter two nerve types were sometimes absent from the middle to caudal basilar artery, owing to a lack of interdigitation by nerves from the internal ethomoidal and vertebral arteries.     

Lateralized phrenic nerve responses to stimulating respiratory afferents in the cat.

We stimulated electrically pharyngeal branch of both glossopharyngeal nerves (PGLN), internal branch of superior laryngeal nerves (ISLN), and carotid sinus nerves (CSN) in anesthetized cats. We recorded simultaneously, averaged, and compared bilaterally evoked phrenic nerve (PHR) activity. Our objective was to demonstrate a short-latency evoked response in the PHR contralateral to the stimulus. Low-intensity stimulation of PGLN and ISLN during inspiration evoked a short-latency contralateral excitation with a latency of 5.2 ms +/- 0.2 SE (16 cats) for PGLN, and 3.8 ms +/- 0.1 SE (13 cats) for ISLN. This excitation could follow stimuli delivered at 100 Hz. Stimulation during expiration did not result in a lateralized excitation. The excitation is followed by bilateral inhibition. Neither strychnine nor picrotoxin prevented either the lateralized response or the inhibition, though strychnine diminished a delayed bilateral excitation following PGLN stimulation. This dalayed (latency 18.7 ms +/- 0.7 SE) bilateral excitation corresponds to the sniff reflex. CSN stimulation did not result in lateralized excitation. We suggest that the lateralized evoked response results from a gated paucisynaptic reflex pathway involving the PGLN and ISLN, ipsilateral inspiratory neurons, and contralateral PHR motoneurons.     

Neural control of sympathetic nerve response to cardiogenic hypotension in anesthetized cat

The present study was designed to determine effect of the preganglionic splanchnic nerve activity (SNA) on the brief hypotension accompanied with the occlusion of left circumflex coronary artery (CxCAO) in chloralose anesthetized cats. Following CxCAO in animals with neuraxis intact, no significant alterations of SNA occurred despite the significant fall in mean blood pressure (MBP). A significant fall in MBP also occurred in vagotomized animals with arterial baroreceptors intact, but SNA was significantly augmented from 12.9 +/- 2.7 impulses/sec before CxCAO to 24.4 +/- 4.3 impulses/sec 60 sec after the occlusion. In vagotomized animals, in which their carotid sinuses were isolated and perfused with the constant pressure at a level equal to systemic blood pressure (112 +/- 6 mmHg) and with higher pressure (167 +/- 7 mmHg), SNA was not altered significantly during the hypotension due to CxCAO. When the carotid sinuses were perfused with lower pressure (53 +/- 8 mmHg), a significant increase in SNA occurred simultaneously with the decrease in MBP after CxCAO. The peak decreases in blood pressure during the coronary occlusion were significantly greater in the vagotomized group (-46 +/- 5 mmHg) and in the Low-CSP group (-50 +/- 5 mmHg) than in other groups. Onset of this excitatory efferent sympathetic response to the hypotension due to the coronary occlusion in the vagotomized and Low-CSP groups was delayed significantly despite a significant fall in arterial blood pressure. These results show that vagal afferents from the heart may play a role of inhibiting the sympathetic augmentation mediated by arterial baroreceptors during cardiogenic hypotension. An excessive activation of cardiac receptors with sympathetic afferents may be induced by the profound fall in blood pressure, resulting in further impairment of cardiac function due to progressive myocardial ischemia under the condition of high sympathetic tone activated by baroreceptor reflex.     

Origin and distribution of cerebral vascular innervation from superior cervical, trigeminal and spinal ganglia investigated with retrograde and anterograde WGA-HRP tracing in the rat

Peripheral sources of cerebral vascular innervation have been investigated with retrograde and anterograde neuronal tracing of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) in the rat. For retrograde identification of sources of innervation, WGA-HRP was applied to the exposed basilar artery through a fine slit in the overlying meninges, and sections of brain and peripheral ganglia were reacted with tetramethylbenzidine for detection of the tracer. A high density of tetramethylbenzidine reaction product was observed around the basilar artery and in the surrounding pial tissue, but the application sites were not completely selective since some tracer always had spread into the ventral brain stem. Retrogradely labelled cell bodies were identified in the superior cervical, stellate, first and second spinal, and trigeminal ganglia, i.e. these ganglia may represent origins of basilar artery innervation. In a second series of experiments, microinjections of WGA-HRP were placed into the indicated ganglia to obtain anterograde labelling of nerve fibres on whole-mounts of the cerebral vessels. Injections into trigeminal ganglia labelled nerve fibres on the ipsilateral half of the circle of Willis, as well as the contralateral anterior cerebral artery and the rostral part of the basilar artery. The first and second spinal ganglia projected to the vertebrobasilar arteries, while the ipsilateral part of the internal carotid (outside the circle of Willis) received fibres from the second spinal ganglion. Nerve fibres originating in trigeminal and spinal ganglia were organised in bundles, and between these a sparse plexus of thin single fibres appeared. Injection of WGA-HRP into superior cervical ganglion labelled a plexus of nerve fibres on the ipsilateral circle of Willis and the (rostral) basilar artery. These experiments demonstrated the origin and distribution of sympathetic and sensory innervation to major cerebral arteries in the rat.