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Biomedical subjects

W G Dail

Publications and source records attributed to W G Dail.

At least 37 records · Page 2Linked to original sources

Penile erection in the rat: stimulation of the hypogastric nerve elicits increases in penile pressure after chronic interruption of the sacral parasympathetic outflow.

Penile erection, a vascular event mediated by the autonomic nervous system, is often adversely affected by injury to the spinal cord. To further characterize the laboratory rat as an animal model of penile erection and to investigate erectile responses following neural injury, the present study has examined pressor penile responses in intact rats and in animals deprived of sacral parasympathetic outflow. Increases in penile pressure result from graded stimulation of postganglionic parasympathetic fibers. The vasodilator response is insensitive to blockade with atropine, a cholinergic antagonist. Penile tumescence also results from stimulation of the pelvic nerve, but not the hypogastric nerve. However, beginning 3 days after unilateral interruption of the pelvic nerve, stimulation of the ipsilateral hypogastric nerve results in an increase in penile pressure. This novel response, which is blocked by a ganglionic antagonist, is maximally developed at 1 week post-lesion, is stable for at least 3 months and remains confined to the side of the lesion. These results suggest that the rat, although relatively small, can be used to obtain quantitative data on penile erection. Moreover, the model may lend itself to an analysis of the mechanisms of altered control of visceral tissues following injury to the nervous system.

Animals↗

Autoradiographic evidence of muscarinic cholinergic receptors in the corpora cavernosa penis of the rat.

Recent studies have questioned the role of acetylcholine in the physiology of penile erectile tissue. The responsiveness of penile erectile tissue to acetylcholine would depend, in part, on the presence of cholinergic receptors on the smooth muscle. The specific binding of [3H]quinuclidinyl benzilate (QNB) to cholinergic receptors in sections of penile crura of the rat was analyzed by in vitro neurotransmitter autoradiography. Silver grain density measurements indicated that muscarinic cholinergic receptor binding sites are located almost entirely over the corpora cavernosa penis. Virtually no specific [3H]QNB binding was present in the tunica albuginea or adjacent skeletal muscle tissue. Within the erectile tissue, specific binding occurred both over the columns of intrinsic smooth muscle which form the walls of the cavernous spaces and around the more distal branches of the penile arteries. The high concentration of muscarinic cholinergic receptors in the corpora cavernosa penis is consistent with the suggestion that acetylcholine has an important, albeit undefined role in the function of penile erectile tissue.

Animals↗

Responses of smooth muscle strips from penile erectile tissue to drugs and transmural nerve stimulation.

1. The mechanical response to drugs and to electrical stimulation of nerves was investigated in isolated strips of intrinsic smooth muscle from the corpora cavernosa penis of the rat. 2. Noradrenaline caused muscle strips to contract in a dose-dependent manner. Contractions could be blocked by pretreatment with the alpha-adrenoreceptor antagonist, phentolamine. 3. Acetylcholine and carbachol had no effect on the baseline tension of muscle strips. Both drugs were relatively ineffective in relaxing noradrenaline-contracted strips. 4. Field stimulation of isolated muscle strips elicited contractions which were blocked by tetrodotoxin and greatly attenuated with phentolamine or reserpine pretreatment. Acetylcholine inhibited the excitatory response to field stimulation. This inhibitory effect of acetylcholine could be blocked with atropine. 5. Field stimulation of noradrenaline-contracted muscle strips caused relaxation. This inhibitory effect, due to nerves which arise from the pelvic plexus, is unaffected by substances which act on cholinergic systems. 6. The results suggest that the erectile muscle of the rat is similar to that of man in that it receives an excitatory noradrenergic innervation and an inhibitory innervation which may have a non-cholinergic component. Although acetylcholine may have a role in penile physiology of the rat, it is unlikely that it has a postsynaptic action.

Acetylcholine↗

Adrenergic innervation of the gills, pulmonary arterial plexus, and dorsal aorta in the neotenic salamander, Ambystoma tigrinum.

The presence of adrenergic innervation was investigated in four different vascular segments of the neotenic tiger salamander, Ambystoma tigrinum, by histofluorescent staining for catecholamines. The segments were the respiratory section of the gill, the branchial shunt vessels, a vascular plexus in the pulmonary artery, and the dorsal aorta. No adrenergic fibers were detected in the respiratory section of the gill or the pulmonary arterial plexus. In contrast, the branchial shunt vessels contained both adrenergic varicosities and catecholamine-containing cell bodies. These cells resemble Type I cells of the mammalian carotid body and amphibian carotid labyrinth. Adrenergic innervation of the dorsal aorta was sparse and restricted to the adventitia. The results suggest that adrenergic nerves may directly regulate blood flow in the gill, and thus gas exchange, by controlling vascular resistance of the branchial shunts. The contractile state of the dorsal aorta may also be under adrenergic control. In addition, it is suggested that the adrenergic cells of the branchial shunts may serve a receptor function in being sensitive to arterial blood gases.

Adrenergic Fibers↗

Composition of the pelvic nerve.

Surgical interruption of the pelvic nerve elevated immunoreactive vasoactive intestinal polypeptide in the major pelvic ganglion of the rat. Two changes were noted: (i) varicose and smooth fibers appeared in the neuropil and (ii) a small number of ganglion cells became highly reactive for the polypeptide. A more proximal transection of preganglionic parasympathetic fibers, at their origin from spinal nerves, had no effect on vasoactive intestinal polypeptide immunoreactivity. Ganglion cells were labeled when a dye was applied to the cut distal end of the pelvic nerve. We conclude that a population of vasoactive intestinal polypeptide-containing neurons in the major pelvic ganglion send their axons proximally in the pelvic nerve.

Animals↗

The hypogastric nerve pathway to penile erectile tissue: histochemical evidence supporting a vasodilator role.

Retrograde dye staining, combined with histochemical and immunohistochemical techniques, were used to characterize penile neurons in the major pelvic ganglion of the rat. Of the penile neurons 92% were immunoreactive for vasoactive intestinal polypeptide, while 95% of penile neurons stained intensely for acetylcholinesterase. None of the neurons were immunoreactive for tyrosine hydroxylase. Penile neurons in the pelvic plexus receive preganglionic input from the pelvic and the hypogastric nerve, yet the shared histochemical features of the postganglionic neurons suggest that the two pathways have a similar role in penile erectile tissue.

Acetylcholinesterase↗

Substance P immunoreactivity in the major pelvic ganglion of the rat.

Substance P immunoreactivity in the major pelvic ganglion (MPG) of the rat was studied to define a possible role for this neuropeptide in functions of the pelvic portion of the autonomic nervous system. Substance P immunoreactivity was found in three locations in the ganglion: 1) as a plexus of varicose fibers, 2) in small intensely fluorescent (SIF) cells, and 3) after colchicine pretreatment, in some principal neurons. The perineuronal plexus of fibers appeared as small varicosities closely related to the somae of principal neurons. Approximately 10-20% of principal neurons were enclosed by a substance P-positive plexus. SIF cells were intensely stained for substance P. The general relationships of SIF cells in this ganglion were confirmed by their staining for substance P: their occurrence singly or in large clusters, their short tapering processes often related to principal neurons, and the occasional presence of a beaded process. Colchicine treatment resulted in the appearance of rare principal neurons that stained for substance P. The pelvic nerve was surgically interrupted to determine whether the perineuronal plexus of varicose fibers had an intrinsic origin or arose from cell bodies outside the ganglion. The perineuronal plexus was virtually absent following this procedure. The results of this study indicate that principal neurons in the major pelvic ganglion may be subject to the influence of substance P derived from two sources: 1) intrinsic substance P-containing SIF cells and 2) neurons probably residing in dorsal root ganglia. The nature of principal neurons that acquire staining for substance P after colchicine is unclear.

Animals↗

The hypogastric nerve innervates a population of penile neurons in the pelvic plexus.

Retrograde dye staining, enkephalin immunocytochemistry and nerve lesion paradigms were used to determine if penile neurons in the pelvic plexus are innervated by fibers in the hypogastric nerve. In the intact major pelvic ganglion of the rat, some 80% of penile neurons are enclosed by an enkephalin-positive fiber plexus. Following surgical interruption of the pelvic nerve, 20% of penile neurons were still surrounded by an enkephalin plexus. After interruption of the pelvic nerve and the hypogastric nerve, the enkephalin plexus in the ganglion was virtually absent, including the plexus around penile neurons. Therefore, possible intrinsic sources of the enkephalin fibers such as enkephalin-positive principal neurons and small intensely fluorescent cells, do not account for the delicate enkephalin fiber system in the pelvic ganglion. It is concluded that the pelvic nerve is the major source of preganglionic innervation to penile neurons in the major pelvic ganglion. However, it is significant that the hypogastric nerve is preganglionic to about 20% of penile neurons. The pathway through the hypogastric nerve may represent an alternate vasodilator system to penile erectile tissue.

Animals↗

Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat.

Vasoactive intestinal polypeptide was localized by immunocytochemical techniques in the major pelvic ganglion and penile erectile tissue of the rat. Vasoactive intestinal polypeptide fibers were concentrated in penile crura with the density of innervation decreasing distally. The helicine arteries were very densely innervated while fewer fibers surrounded the deep artery of the penis. Intrinsic smooth muscle of the cavernous bodies received a moderate supply of vasoactive intestinal polypeptide immunoreactive fibers. Dorsal vascular structures, including the deep dorsal vein were innervated by vasoactive intestinal polypeptide fibers. Vasoactive intestinal polypeptide immunoreactive cell bodies were found in the major pelvic ganglion, concentrated on one end of the ganglion. Retrograde studies with a dye injected into the penile crura indicated that neurons in major pelvic ganglion projected to the penis. Combined dye and immunofluorescent studies showed that all the dye-labeled neurons were immunoreactive for vasoactive intestinal polypeptide. It is concluded that all vascular beds in the penis of the rat are innervated by vasoactive intestinal polypeptide fibers and that the extent of the innervation is related to the occurrence of smooth muscle. Neurons in the major pelvic ganglion probably are the main source of vasoactive intestinal polypeptide fibers to the penis.

Animals↗

Modified radical mastectomy with immediate breast reconstruction.

Surgery for breast cancer continues to evolve. Less radical procedures and increasing concern about appearance and rehabilitation are now the trend. Such considerations prompted a detailed anatomic study and review of the location and course of the medial and lateral pectoral nerves, the development of a technique for immediate reconstruction of the breast during modified radical mastectomy that protects the innervation of the pectoral muscles and incorporates them in the construction of a submuscular pocket to receive a silicone breast prosthesis, and the administration of low doses of heparin sodium to prevent necrosis of ischemic breast flaps. Fifty immediate reconstructions of the breast after modified radical mastectomy were performed in 48 women with carcinoma of the breast. We believe this procedure greatly enhances rehabilitation and quality of life without diminishing the ability to diagnose or treat recurrent disease.

Adult↗

The Manx cat as an animal model for neurogenic vesical dysfunction associated with myelodysplasia: a preliminary report.

The Manx cat breeds consistently for spinal dysraphism (myelodysplasia) and has spinal cord neuropathologic abnormalities similar to those of myelodysplastic humans. The results of detailed urodynamic and histochemical evaluation of 1 Manx kitten and limited anatomic study of another Manx kitten are described. Urodynamic evaluation revealed significant abnormalities of vesicourethral function: detrusor areflexia, autonomous pressure response to bladder filling, a dysfunctional proximal urethra and poor quality pelvic floor electromyographic activity. Of particular interest, catecholaminergic histochemical studies of the bladder and urethra demonstrated a complete absence of adrenergic fibers, even in the trigone area where they are reported to be abundant. This finding correlated with the urodynamic dysfunction of the proximal urethra. Cholinergic histochemical studies were normal. Examination of the spinal cord revealed moderate hydromyelia throughout the entire length of the cord. The similarities of normal vesicourethral function in man and the cat and our preliminary findings of vesicourethral dysfunction in the Manx cat suggest that this animal may be a particularly valuable model for further research.

Adrenergic Fibers↗

Evidence for direct neural control of ovarian steroidogenesis in rats.

Electrical stimulation of the superior ovarian nerve of intact anaesthetized dioestrous rats for 30 min reduced ovarian progesterone levels, even when papaverine and propranolol were also given. The administration of phentolamine (an alpha receptor antagonist) before stimulation reversed this effect. The results suggest that a neural control of ovarian steroidogenesis may be either excitatory through the stimulation of beta receptors or inhibitory through the stimulation of alpha receptors.

Animals↗

Responses to cortical injury: I. Methodology and local effects of contusions in the rat.

In order to develop some understanding of the evolution of cortical contusions, interdisciplinary studies including behavior, morphology and histochemistry were conducted at varying intervals after standardized injuries. A method for producing graded and reproducible focal cortical contusions in the rat is described. When these impact injuries are made in the "hindpaw cortical area,' specific trauma dose dependent behavioral deficits can be readily observed in the contralateral hindlimb. While most functional recovery occurs in the first two weeks after trauma, with severe contusions, deficits persist beyond 90 days. Morphologically these injuries progress from hemorrhages in white matter directly under contused cortex during the first hours after injury to the development of a necrotic cavity by 24 hours. The cavitation appears to expand over the subsequent two weeks and by 15 days is lined with fibroblast-like elements and macrophages. Intense acid phosphatase activity is seen on the borders of the area of necrosis. This lysosomal enzyme may participate in autolysis and development of focal cavitation following cortical contusion.

Acid Phosphatase↗

Responses to cortical injury: II. Widespread depression of the activity of an enzyme in cortex remote from a focal injury.

As a part of a broader study of the reaction of the brain to injury, we report here an interesting loss of the activity of an enzyme in areas quite remote from the site of direct injury. At 36 h following a laceration or contusion injury to the hindpaw area of the motor cortex, a peculiar loss of staining for the enzyme alpha glycerophosphate dehydrogenase (alpha-GPDH) was noted. alpha-GPDH activity was markedly depressed in cortical layers II and III throughout the hemisphere on the side of the injury. The depression of alpha-GPDH activity extended far laterally across the rhinal fissure into the pyriform cortex. The decrease in alpha-GPDH staining was prominent 4 days after the injury: however, the staining pattern had returned to normal at 9 days. Enzyme changes in animals lesioned in the occipital cortex paralleled that seen in animals with a lesion in the motor cortex. Animals which had received an undercut lesion in the motor cortex 56 days earlier were contused in the occipital cortex. The old injury site presented the same sequelae of changes as seen in other lesioned animals. Additionally, a suction ablation injury involving only a small part of motor cortex resulted in the same widespread reduction of staining for alpha-GPDH in layers II and III. The derangement in energy metabolism suggests that cells in layers II and III of the cerebral cortex may be particularly vulnerable to perturbations induced by cortical trauma. These findings may be related to the diffuse and transient functional losses observed after head injury in man.

Animals↗

Cardiac catecholamine stores after cardiac sympathectomy, 6-OHDA, and cardiac denervation.

Sympathetic nerves are known to reach the heart via classical vagal pathways. Bilateral cervicothoracic sympathectomy (CS) might be expected therefore to leave significant amounts of releasable catecholamines in the myocardium if the vagi are left intact. Cardiac responses to tyramine (500 micrograms intracoronary) were compared in animals with CS, extrinsic cardiac denervation (CD), and chemical sympathectomy with 6-hydroxydopamine (6-OHDA). Dogs were placed on cardiopulmonary bypass and isovolumic pressures were recorded from the heart. In control animals, tyramine caused profound increases in rate (58%) and isovolumic pressures (86-170%). Ten CS animals demonstrated responses indistinguishable from control animals. Four CD and four 6-OHDA animals showed no response to tyramine. Cervical vagal stimulation after atropine in the CS animals produced tachycardia. Histofluorescent studies demonstrated the presence of significant numbers of cardiac adrenergic fibers in this group. The normal tyramine responsiveness of the CS animals was attributed to 1) significant numbers of vagal adrenergic fibers remaining in the heart after cervicothoracic sympathectomy, and 2) denervation supersensitivity, rendering the heart very responsive to the catecholamine that remains.

Animals↗

Effects of p-chloroamphetamine, a serotonin-depleting drug, on the median eminence and pituitary pars intermedia.

p-Chloroamphetamine (PCA), an agent known to cause depletion of levels of brain serotonin in rodents, was administered to rats in three sequential injections (10mg/kg) to study effects on the hypothalamic median eminence and pituitary gland. One week following the initial sequence of injections of PCA, light and electron micrographs revealed degenerate fibers in the outer zone of the median eminence. Lower drug doses or single 10-mg/kg doses did not lead to morphologic changes. Neuronal processes located in the pituitary intermediate lobe appeared normal although there was a significant increase in the numbers of secretory granules contained within intermediate lobe cells drug-treated rats, as compared to controls. Fluorometric analysis of levels of catecholamine and indoleamine showed a decrease in serotonin in median eminence and pons-medulla, but no change in that of the pituitary. Levels of dopamine and norepinephrine remained unchanged after PCA treatment. The data suggest that fibers affected in the median eminence contain serotonin. Processes in the intermediate lobe may be resistant to the serotonin-lowering effects of PCA observed in brain tissue. In addition, PCA may directly affect granule release from pituitary cells, or may alternatively act on hypothalamic regions which affect the release of intermediate lobe cell hormones.

Animals↗