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Biomedical subjects

A M Booth

Publications and source records attributed to A M Booth.

32 records · Page 2Linked to original sources

Use of intracoronary KCl in the beating and asystolic heart to determine the mechanism of initiation of the left ventricular mechanoreceptor reflex.

To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkaloids, but with a negative inotropic effect, was studied in beating and verapamil-asystolic hearts. Five dogs were placed on a total cardiac bypass, pneumonectomised and their coronary and systemic circulations isolated and perfused separately, at a constant rate, so that changes in systemic pressure reflected changes in systemic resistance. Injection of 5 mmol X litre-1 KCl into the isolated coronary circulation caused cardiac asystole and a resultant reflex rise in systemic pressure (resistance) of 26 +/- 9% (p less than 0.05) above the control of 10.5 +/- 0.7 kPa (79 +/- 5 mmHg). This pressure rise, which indicates predominance of KCl's mechanical, negative inotropic over its chemical depolarising effect, was abolished by vagotomy, indicating its reflex nature. Contrariwise, in five other pneumonectomised dogs, similarly perfused on total cardiac bypass but with cardiac asystole from intracoronary verapamil, a subsequent, similar intracoronary dose of KCl now produced a fall in systemic pressure (resistance) of 8 +/- 2% (p less than 0.005) below the control of 12.8 +/- 0.5 kPa (96 +/- 4 mmHg). This pressure fall, presumably due to chemical depolarisation of the left ventricular mechanoreceptors, was also abolished by vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The presence of leucine-enkephalin in the sacral preganglionic pathway to the urinary bladder of the cat.

Leucine-enkephalin (L-ENK) nerve terminals which surround the cholinergic neurons in ganglia of the cat urinary bladder are eliminated after transection of the sacral ventral roots or the pelvic nerve. These findings, coupled with other anatomical and physiological data, suggest that L-ENK may be a cotransmitter with acetylcholine in the sacral preganglionic pathways to the urinary bladder.

Animals↗

Parasympathetic ganglia: naloxone antagonizes inhibition by leucine-enkephalin and GABA.

Synaptic transmission in parasympathetic ganglia of the cat urinary bladder was depressed by low doses (0.1-10 micrograms i.a.) of Leu- or Met-enkephalin but only by larger doses (10 micrograms-1 mg i.a.) of morphine. Naloxone blocked the depressant effects of the opiates as well as the depression produced by GABA, but did not block the depressant effects of norepinephrine. Intracellular recording revealed that Leu-enkephalin reduced EPSP-amplitude and lowered the probability of synaptically evoked firing without altering postsynaptic membrane potential or resistance. These findings suggest that enkephalinergic inhibition in bladder ganglia is mediated at least in part by a presynaptic site of action on delta opiate receptors.

Animals↗

The effects of naloxone on the neural control of the urinary bladder of the cat.

Naloxone in doses ranging from 0.5 to 512 micrograms/kg i.v., enhanced reflex contractions of the urinary bladder of the cat. At the lowest doses (threshold, 0.5-5 micrograms/kg) the drug increased the frequency of spontaneous bladder contractions. In large doses (10-100 micrograms/kg) the drug produced an initial tonic contraction of bladder lasting 15-40 min followed by a period of high frequency rhythmic activity. Multiunit firing in parasympathetic postganglionic nerves on the surface of the urinary bladder was also enhanced. Bursts of firing which in untreated animals occurred during large bladder contractions occurred continuously during the entire sustained contraction of the bladder following large doses of naloxone. Various evidence indicates that the site of action of naloxone is in the central nervous system. These findings suggest that the parasympathetic reflex pathway to the urinary bladder may be subject to tonic enkephalinergic inhibitory control.

Animals↗

Parasympathetic preganglionic neurons in the sacral spinal cord.

Two types of preganglionic neurons have been identified in the sacral parasympathetic nucleus (SPN) of the cat. These neurons could be differentiated by various characteristics including axonal conduction velocities, morphology, location in the nucleus, organ of innervation and central reflex mechanisms controlling their activity. Neurons having myelinated axons (B-PGNs) with conduction velocities between 3.3 and 13 m/s were located in the lateral band of the SPN and innervated the urinary bladder. Neurons with unmyelinated axons (C-PGNs) with conduction velocities of 0.5-1.4 m/s were located in the dorsal band of the nucleus and innervated the large intestine. B-PGNs were excited by distention of the bladder and inhibited by distension or mechanical stimulation of the intestine, whereas C-PGNs exhibited the opposite responses to these stimuli. C-PGNs often exhibited a low level of spontaneous discharge in absence of stimulation but exhibited marked firing (3.5-10 spikes/s) during a defecation reflex elicited by mechanical stimulation of the rectum-anal canal. The excitatory responses were elicited by C-fiber afferents via a spinal reflex pathway. B-PGNs were inactive when intravesical pressure was below the threshold for inducing micturition (5 cm H2O) but raising the pressure above the threshold induced firing consisting of repetitive bursts of action potentials occurring at relatively high frequencies (15-60 spikes/s). These bursts coincided with rhythmic bladder contractions. The frequency of bladder contractions and associated bursts of PGN-firing and the mean PGN-firing rate (2-8 spikes/s) increased as intravesical pressure was increased in steps between 5 and 30 cm H2O. However, as indicated by interspike interval histograms, the frequency of firing within a burst of action potentials was unchanged. It is concluded that the micturition reflex pathway is organized as a simple on-off switching circuit and that B-PGNs receive a maximal synaptic input when intravesical pressure exceeds the micturition threshold. This circuit was triggered by vesical A delta afferents via a spinobulbospinal pathway. Transection of the spinal cord interrupted the reflex pathway and blocked micturition. However, in chronic spinal animals a spinal reflex mechanisms emerged which contributed to the recovery of bladder function. This mechanism, which was weak or non-existent in animals with an intact neuraxis, exhibited a number of important differences from the normal micturition reflex, most notably being activated by a C-fiber afferent rather than a A delta afferent limb. The mechanism underlying the emergence of C-fiber evoked bladder reflexes in spinal animals is uncertain.

Action Potentials↗

Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine.

Electrophysiological and horseradish peroxidase (HRP) techniques have provided new insights into the organization of the sacral parasympathetic reflex pathways to the large intestine and urinary bladder. The innervation of the two organs arises from separate groups of sacral preganglionic cells: (1) a dorsal band of cells in laminae V and VI providing an input to the intestine; and (2) a lateral band of cells in lamina VII providing an input to the bladder. These two groups of cells were separated by an interband region containing tract cells and interneurons. Neurons in the interband region received a visceral afferent input and exhibited firing correlated with the activity of intestine and urinary bladder. It seems reasonable therefore to consider the interband region as a third component of the sacral parasympathetic nucleus. Anterograde transport of HRP revealed that visceral afferents from the intestine and bladder projected into the parasympathetic nucleus. Most of the projections were collaterals from afferent axons in Lissauer's tract that passed in lamina I laterally and medially around the dorsal horn. These afferent collaterals were located in close proximity to preganglionic perikarya and dendrites in laminae I, V and VI. The proximity of visceral afferents and efferents in the sacral cord probably reflects the existence of polysynaptic rather than monosynaptic connections since electrophysiological studies revealed that both the defecation and micturition reflexes occurred with very long central delays (45-70 msec). The reflex pathways mediating defecation and micturition in cats with an intact neuraxis were markedly different. Defecation was dependent upon a spinal reflex with unmyelinated (C-fiber) peripheral afferent and efferent limbs. On the other hand, micturition was mediated by a spinobulbospinal pathway with myelinated peripheral afferent (A-fiber) and efferent axons (B-fiber). Transection of the spinal cord at T12-L2 blocked the micturition reflex but only transiently depressed the defecation reflex. In chronic spinal cats the micturition reflex recovered 1-2 weeks after spinalization; however, in these animals bladder-to-bladder micturition reflexes were elicited by C-fiber rather than A-fiber afferents. The C-fiber afferent-evoked reflex was weak or undetectable in animals with an intact neuraxis. Transection of the spinal cord also changed the micturition reflex in neonatal kittens (age 5-28 days). In neonates with an intact neuraxis bladder-to-bladder reflexes occurred via a long latency spinobulbospinal pathway (325-430 msec). The long latency is attributable to the slow conduction velocity in immature unmyelinated peripheral and central axons. In chronic spinal kittens (3-7 days after spinalization) the long latency reflex was abolished and a shorter latency (90-150 msec) bladder reflex was unmasked. The emergence of this spinal pathway may reflect axonal sprouting and the formation of new reflex connections within the sacral parasympathetic nucleus.

Afferent Pathways↗

Physiology of the urinary bladder and urethra.

Activation of the parasympathetic pathways to the detrusor muscle and inhibition of somatic input to the external urethral sphincter are the essential neuronal events initiating release of urine. The former occurs via a spinobulbospinal pathway, whereas the latter is produced by inhibitory mechanisms in the sacral spinal cord. The sympathetic outflow to the urinary tract promotes urine storage by increasing urethral resistance and depressing detrusor contractions. Sympathetic activity is generated at least in part by a spinal vesicosympathetic reflex pathway. Evidence indicates that the integration of sympathetic and parasympathetic inputs to the bladder can occur at the level of the peripheral autonomic ganglion as well as at levels of the effector organ. The existence of facilitatory and adrenergic inhibitory mechanisms in ganglia and the identification of spontaneously active ganglion cells raise the possibility that vesical ganglia may have a role in modulating or "filtering" the efferent neural input to the bladder.

Animals↗

Physiology of male sexual function.

The male sexual response cycle consists of excitement, plateau, orgasm, and resolution. The initial event, penile erection, is produced by arteriolar dilatation and increased blood flow to the erectile tissue of the penis. Erection is a reflex response initiated by visual, olfactory, or imaginative stimuli impinging upon supraspinal centers or by genital stimulation that in turn activates spinal reflex mechanisms. Sacral parasympathetic and thoracolumbar sympathetic nerves provide the efferent vasodilator input to the penis. Parasympathetic nerves also stimulate secretion from the seminal vesicles and prostate and Cowper's glands during the plateau phase. The orgasmic phase is characterized by seminal emission and ejaculation and the accompanying sensations. Emission of semen into the urethra depends on sympathetic nerves that elicit contractions of smooth muscles in the vas deferens, seminal vesicles, and prostate. Rhythmic contractions of striated muscle (bulbocavernosus and ischiocavernosus) generated by efferent pathways in the pudendal nerve eject semen from the urethra.

Animals↗

Inhibition and facilitation in parasympathetic ganglia of the urinary bladder.

Neurons in vesical parasympathetic ganglia receive excitatory and inhibitory inputs from both divisions of the autonomic nervous system. Sacral parasympathetic pathways (cholinergic) provide the major excitatory input to these ganglia via activation of nicotinic receptors. Parasympathetic pathways also activate muscarinic inhibitory and excitatory receptors, which may exert a modulatory influence on transmission. Cholinergic transmission is relatively inefficient when preganglionic nerves are stimulated at low frequencies (< 1 Hz). However, excitatory postsynaptic potentials (EPSPs) and postganglionic firing markedly increase during repetitive stimulation at frequencies of 1-10 Hz. It is concluded that enhanced transmitter release accounts for the temporal facilitation and that vesical ganglia function as "high pass filters" that amplify the parasympathetic excitatory input to the detrusor muscle during micturition. Transmission in vesical ganglia is also sensitive to adrenergic inhibitory and facilitatory synaptic mechanisms elicited by efferent pathways in the hypogastric nerves. The effects of exogenous norepinephrine indicate that adrenergic inhibition is mediated by alpha receptors and reflects primarily a presynaptic depression of transmitter release although postsynaptic adrenergic hyperpolarizing and depolarizing effects have also been noted. Adrenergic facilitation is mediated by beta receptors as well as unidentified receptors. Norepinephrine also can inhibit or excite spontaneously active neurons in vesical ganglia. The existence of inhibitory and facilitatory synaptic mechanisms in vesical ganglia provides the basis for a complex ganglionic modulation of the central autonomic outflow to the bladder.

Animals↗

Pediatric angiosarcoma of the heart: a unique presentation and metastatic pattern.

We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII-related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed.

Antigens, Neoplasm↗

The role of neuropeptides in the sacral autonomic reflex pathways of the cat.

Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve terminals in peripheral ganglia on the surface of the urinary bladder and in the parasympathetic nucleus in the sacral spinal cord. In colchicine-treated animals L-Enk was also detected in sacral preganglionic neurons (sPGN) identified by retrograde transport of a fluorescent dye. L-Enk terminals in bladder ganglia are believed to arise from sPGN since the terminals were eliminated by transection of the sacral ventral roots. Pharmacological studies indicated that exogenous as well as endogenously released enkephalins have an inhibitory action at both ganglionic and spinal sites in the sacral outflow to the urinary bladder. Peptides were also associated with afferents nerves in the sacral autonomic system. The distribution of substance P, VIP and cholecystokinin in the sacral dorsal horn paralleled the distribution of visceral afferent projections as demonstrated with HRP techniques. Dye labeling combined with immunohistochemistry revealed that some dorsal root ganglion cells projecting to the pelvic viscera contain substance P or VIP.

Animals↗