Constricted Nerve Research Articles

Changes in oxygen consumption in the hindlimb of the cat during various forms of vasodilation.

The influence of various vasodilating agents on the oxygen consumption was studied in the hindlimb of the cat. During the increase in flow by means of papaverine, acetylcholine, bradykinin, cobaltous chloride, isoprenaline, and phentolamine, an initial increase in the oxygen consumption for about 30 to 60 sec was observed. This phase was immediately followed by a sustained reduction in oxygen uptake below the control value although the blood flow remained increased. The diminution was greater than the initial elevation in oxygen uptake and was correlated with the increase in blood flow. An inhibition of the sympathetic constrictor nerve activity did not influence the biphasic changes in oxygen consumption due to the vasodilating agents. The blockade of the sympathetic vasoconstrictor tone led itself to a vasodilation, which was accompanied by an elevation of oxygen uptake during the whole period of flow increase. It is suggested that a shift in the pattern of flow within the extremity is responsible for these changes in oxygen consumption following the administration of the vasodilating agents tested here.

Intraaxonal migration of [ 3H]norepinephrine injected into the coeliac ganglion of cats: radioautographic study of the proximal segment of constricted splenic nerves

Intraaxonal migration of [ 3H]norepinephrine injected into the coeliac ganglion of cats: radioautographic study of the proximal segment of constricted splenic nerves

Catecholamine transport in constricted nerve fibers of the toad

Biochemical data have been correlated with fine structural features to study CA transport in adrenergic fibers of the toad. It was found that the rate of cellulifugal transport of CA in the sciatic nerve of this species is 7 mm per 24 hr. Both CA and granulated vesicles were found to accumulate almost linearly in dammed up portions of nerves ligated for zero, 24, 48 and 72 hr. On the basis of the electron microscopic observations it is postulated that the granulated vesicles (CA storage particles) originate from membrane-bounded canaliculi and assumed, therefore, that CA are transported down the toad adrenergic axons within the lumina of the smooth endoplasmic reticulum.

Organelle transport in constricted nerve fibers of the toad Bufo arenarum Hensel.

The splanchnic nerves of toads were tightly ligated and the organelles present both on the proximal and the distal side of the constriction were counted after zero, 24 and 48 hrs. Swelling of the fibers and accumulation of mitochondria and of smooth canaliculi were found to be the most conspicuous expressions of damming in the nerve segments above the constriction. No changes in the microtubule population or in the ratio of dense-core microtubules to empty microtubules were observed. A progressive collection of granulated vesicles is described for a minority of fibers in the segment proximal to the ligature. Evidence is presented in support of the view that such granulated vesicles are budded from swollen canaliculi. Fine structural expressions of damming were not found in the nerve segments distal to the constriction.

The effects of iproniazid and reserpine on the accumulation of granular vesicles and noradrenaline in constricted adrenergic nerves.

1. The accumulation of granular vesicles proximal to a constriction applied to hypogastric nerves has been investigated with the electron microscope in cats treated with reserpine and/or iproniazid.2. The ultrastructural changes have been correlated with the accumulation of noradrenaline at the same site in similarly treated animals.3. The findings give further support to the view that granular vesicles constitute a major storage site for intraneuronal noradrenaline.

The re-distribution of cytochrome oxidase, noradrenaline and adenosine triphosphate in adrenergic nerves constricted at two points.

1. The experiments correlate certain changes in the ultrastructure of cat hypogastric nerves constricted at two points with the distribution of a mitochondrial enzyme (cytochrome oxidase), noradrenaline (stored in some of the vesicles with an electron dense core, i.e. granular vesicles) and adenosine triphosphate (ATP) (present in noradrenaline storage granules, mitochondria and the soluble fraction of the axon).2. Noradrenaline (NA) and granular vesicles accumulated proximal but not distal to both constrictions. The total amount of NA and the concentration of granular vesicles above the first constriction was greater than that present in a similar piece of normal nerve, indicating that the cell body was continuing to produce the transmitter despite injury to its axon. The granular vesicles proximal to the first constriction were found in swollen or distorted axons and in new axonal outgrowths. It was concluded that the movement of NA in these constricted nerves was only centrifugal in direction.3. Mitochondria and cytochrome oxidase accumulated on both sides of the two constrictions, indicating a bi-directional movement of mitochondria in the damaged axons. The possibility that some of the increase in the cytochrome oxidase could be related to an increase in the number of mitochondria in cells other than neurones is considered.4. The adenosine triphosphate content increased on both sides of the two constrictions. This increase developed more slowly and was less marked than that of the other two substances.5. It was concluded that (a) there was a close correlation between the behaviour of noradrenaline and granular vesicles and between cytochrome oxidase and mitochondria, (b) the dense cored vesicles and the mitochondria moved independently of one another and at different rates after constriction of non-myelinated axons, (c) while some of the changes may be attributed to an obstruction to the free movement of axoplasm others may be due to an active reaction to axonal injury, and (d) localized intraaxonal synthesis of noradrenaline and cytochrome oxidase did not occur between the two constrictions.

Muscular, bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract.

1. The effects of mechanical stimulation in the nose, epipharynx, laryngopharynx and tracheobronchial tree, and of chemical irritation of the nasal mucosa, were studied on various somatic and autonomic functions in cats.2. Action potentials were recorded from the diaphragm and rectus abdominis muscles of spontaneously breathing cats, and from the phrenic and lumbar nerves of paralysed, artificially ventilated cats. Expulsive processes such as sneezing and coughing evoked from the nasal, laryngopharyngeal and tracheobronchial mucosae were characterized by strong diaphragmatic and abdominal expiratory discharges; synchronous discharges in these antagonistic respiratory muscles and their motoneurones often occurred especially during laryngopharyngeal stimulation of coughing.3. The ;aspiration reflex' elicited from the epipharynx was characterized by brief bursts of high-frequency activity in the phrenic nerve and diaphragm, and was usually not followed by any expiratory activity in the rectus abdominis or its motoneurones.4. In paralysed, artificially ventilated cats stimulation of the laryngeal and tracheobronchial regions caused large increases both in total lung resistance and in tracheal constrictor nerve fibre activity, indicating reflex tracheo-bronchoconstriction; similar stimulation of the epipharyngeal and nasal mucosae decreased both total lung resistance and tracheal constrictor nerve fibre activity, indicating reflex bronchodilation.5. In paralysed cats, stimulation of each of the four sites in the respiratory tract caused a reflex increase in systemic blood pressure, the largest hypertensive response coming from the epipharynx. Nervous activity in cervical sympathetic efferent fibres was increased by the stimulations, especially those of the epipharyngeal and laryngopharyngeal regions.6. There was good correlation in time and magnitude between the changes in total lung resistance and in bronchoconstrictor fibre activity, and also between the changes in blood pressure and in efferent sympathetic discharge, although the mechanical changes lagged behind the nervous ones.7. In anaesthetized, spontaneously breathing cats stimulation of the respiratory tract evoked large variations in blood pressure accompanying the spasmodic respiratory efforts, probably by mechanical effects.

Fine structural localization of acetylcholinesterase at a cholinergic vasodilator nerve-arterial smooth muscle synapse.

An electron-microscope study of the localization of acetylcholinesterase (AChE) has been made in the main uterine artery of the guinea pig, which is supplied by cholinergic dilator and adrenergic constrictor nerves. Large bundles of nonterminal axons were present in the outer adventitia, and terminal axons, containing numerous vesicles, were scattered through the inner adventitia up to 1µ away from the outer layer of smooth muscle cells. About 50% of these axons were within 0.2µ of a muscle cell; the minimum neuromuscular gap found was 0.05µ. No axons were within the media. The outer membranes of axons stained either heavily or lightly for AChE. These two distinct classes appear to represent cholinergic and noncholinergic axons, respectively. In late pregnancy, all cholinergic terminal axons which contained vesicles and were not separated from the muscle by Schwann or elastic tissue were associated with heavy postsynaptic staining which was restricted to that region of the muscle membrane adjacent to the axon. In tissue from virgin animals, most cholinergic terminal axons were associated with only scanty postsynaptic staining. The increase in postsynaptic AChE during pregnancy can be correlated with the increase in sensitivity of the arterial muscle to acetylcholine over this period. Assuming that the association of heavy AChE staining both pre- and postsynaptically is indicative of a functional cholinergic synapse, acetylcholine released up to 1µ away from the muscle may participate in transmission from vasodilator axons in this vessel. Since postsynaptic AChE staining is restricted to discrete areas on the outer muscle cells, probably only these cells are directly affected by transmitter released from nerves.

The accumulation of noradrenaline in constricted sympathetic nerves as studied by fluorescence and electron microscopy.

The effects of constricting post-ganglionic sympathetic nerves have been studied in the cat splenic nerve and guinea-pig hypogastric nerve. The results obtained using a fluorescence method for the histochemical localization of noradrenaline have been compared with electron microscopic findings. A close correlation was found between the accumulation of fluorescent material, attributable to noradrenaline, and of vesicles with an electron dense core (granular vesicles) believed to contain noradrenaline, proximal to the constriction in these nerves. This accumulation of noradrenaline was visible by 1 h after operation and increased rapidly in amount during the succeeding hours. It apparently reached a maximum after approximately 2 days and was found in what appeared to be newly formed axons 3 to 4 days after operation. Reserpine reduces the fluorescence and the number of vesicles with electron dense cores which accumulate proximal to the constriction. It is suggested, (1) that the fluorescent material is due, at least in part, to the presence of the granular vesicles, and (2) that the constriction has blocked the normal proximo-distal movement of noradrenaline which is believed to occur in post-ganglionic sympathetic axons.

The control of the circulation in skeletal muscle during arterial hypoxia in the rabbit.

1. The effects of arterial hypoxia on muscle blood flow were examined in normal unanaesthetized rabbits in relation to simultaneously determined changes in cardiac output, arterial pressure and heart rate. Muscle blood flow was estimated from the difference between total limb flow (local thermodilution) and the estimated skin flow (using a calibrated heat conductivity method). The role of the arterial chemoreceptors and baro-receptors in the control of muscle blood flow was examined and the nature of the sympathetic efferent discharge analysed.2. In mild hypoxia (P(O2) > 35 mm Hg) in the rabbit, muscle blood flow did not change, although cardiac output increased. During moderate hypoxia (P(O2) 30-35 mm Hg) there was initial vasoconstriction in muscle, followed by a return to control values paralleling the changes in cardiac output. In severe arterial hypoxia (P(O2) < 30 mm Hg) the initial vasoconstriction was less marked, and during the ;steady state' there was a large vasodilatation and increase in muscle blood flow, at a time when the cardiac output was not elevated.3. The early vasoconstriction in arterial hypoxia is mediated mainly through sympathetic vasoconstrictor nerves as a result of strong arterial chemoreceptor stimulation.4. Increased secretion of adrenaline is an important factor in restoring muscle blood flow to control values during moderate arterial hypoxia, and in elevating the muscle blood flow above these values in severe hypoxia. The peripheral dilator (beta-) effects of adrenaline oppose the peripheral constrictor (alpha-) effects resulting from increased activation of sympathetic constrictor nerves during arterial hypoxia.

EFFECT OF HEMORRHAGIC SHOCK ON THE REACTIVITY OF RESISTANCE AND CAPACITANCE VESSELS AND ON CAPILLARY FILTRATION TRANSFER IN CAT SKELETAL MUSCLE.

During hemorrhagic shock there is impairment, and eventually abolition, of the responses of both the resistance and the capacitance vessels in cat skeletal muscle to regional lumbar sympathetic vasoconstrictor nerve fiber stimulation and to close intra-arterial infusion of l -norepinephrine. The rate of decline of reactivity is faster, and the time to abolition shorter, for the resistance response than for the capacitance response. Also, the pre-capillary resistance response declines faster and is abolished earlier than the post-capillary resistance response. This impairs and eventually abolishes the ability of constrictor nerve stimulation to decrease mean capillary hydrostatic pressure, and, thereby, causes a net inward movement of extravascular fluid. Preservation of the post-capillary response beyond that of the pre-capillary results eventually in a net outward movement of capillary fluid on nerve stimulation. Replacement of the shed blood restores vascular reactivity to normal. This can occur even when nerve stimulation results in a net loss of capillary fluid, but may not, if this period of shock has been very long. The evidence indicates that pre-capillary functions (small arteries, arterioles, and pre-capillary sphincters) are more under the influence of local metabolic factors than of extrinsic nervous influence. On the other hand, post-capillary functions (post-capillary resistance vessels, and main capacitance vessels) are more dominated by extrinsic nervous influence. However, even in this section the nervous influence may be overcome by relatively large concentrations of "metabolites" as is seen late in the period of hemorrhagic shock. From the results obtained here, it is suggested that early in hemorrhagic shock the sympathetics, at least with respect to skeletal muscle, act in a compensatory manner by maintaining "venous return" (maintained capacitance response) and by increasing circulating blood volume (inward movement of extravascular fluid). The dominant action of local dilator factors on pre-capillary functions has the effect of limiting the magnitude of nerve-induced increased resistance to blood flow and, by impairing the reactivity of the pre-capillary sphincters, distributes the available blood flow over a greater than normal fraction of the capillary bed. Late in the course of hemorrhagic shock, with abolition of pre-capillary responses, the action of the sympathetics would appear to be decompensatory, in that they cause a loss of fluid from the capillaries. This phenomenon may provide a partial explanation for the observed beneficial effect of sympatholytic agents in hemorrhagic shock. The sequence of deteriorating vascular reactivity in skeletal muscle, while not necessarily representative of all tissues, serves to explain many of the hitherto puzzling features of the peripheral vasculature in shock. It also suggests a mechanism, common to all states with reduced tissue blood flow, that may explain lack of response to treatment.

Endoneurial edema in constricted nerve

Endoneurial edema in constricted nerve

An analysis of the relations of the coronary constrictor and dilator nerves in the cervical vagosympathetic of the dog

1. 1. Vagosection was performed above the ganglion nodosum. The animals were allowed to recover and the nerves to undergo a variable period of degeneration and repair after which functional tests were applied. 2. 2. Dogs with vagosection exhibit a total, or almost total, loss of coronary constriction in response to cervical vagosympathetic stimulation. Two animals have shown a mild degree of coronary constriction after cervical dilator control was reduced by injections of nicotine into the cervical sympathetic ganglia. 3. 3. These more distally placed coronary constrictor neurones have only a moderate total effect and are not always present. A satisfactory explanation of this occasional type of animal is that some few neuroblasts have migrated distally in early embryonic development. 4. 4. The loss of coronary constriction after vagotomy and degeneration indicates that the vagus is the sole pathway of the efferent coronary constrictor nerves. 5. 5. After the coronary constrictors are degenerated, stimulation of the cervical vagosympathetic produces coronary dilation of variable amount. 6. 6. Coronary dilation from stimulation of the cervical vagosympathetic trunk after vagal degeneration does not occur in all animals, and varies in amount from nothing to a medium degree of dilation among those animals in which it is present. 7. 7. There is greater reaction to stimulation of the lower cervical region just above the inferior cervical ganglion. A definite palpable middle cervical ganglion is rarely present in the dog. Histological sections, however, show that strands of nerve cells may be present among the bundles of axones of the vagosympathetic trunk at approximately the region of the middle cervical ganglion. These cells function as links in the chain of efferent coronary dilator pathways. 8. 8. Cardiac inhibitory fibers were completely absent from the degenerated vagi of the animals reported in this series.

THE INFLUENCE OF EPINEPHRIN UPON THE CORONARY CIRCULATION OF THE MONKEY

Decrease in coronary flow was the constant response of freshly isolated monkey hearts to epinephrin. These hearts were perfused with autogenous hirudinized blood diluted with Locke solution. The results were constant at high or low perfusion pressures, in beating or resting hearts, and with all adequate doses. Increased coronary flow was obtained constantly in rabbit hearts under identical conditions. In the light of previous work upon isolated human coronary arteries, the general conclusion is drawn that, while actively dilating the coronary vessels in the dog, cat, rabbit, ox, sheep, and pig, epinephrin constricts the coronary vessels in man and the monkey. The coronary arteries of the last two species are presumably supplied with constrictor nerves of true sympathetic (thoracicolumbar) origin.