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Biomedical subjects

R M Robertson

Publications and source records attributed to R M Robertson.

At least 19 recordsLinked to original sources

Administration of dexfenfluramine in pregnant rats: effect on brain serotonin parameters in offspring.

Dexfenfluramine (DFEN) was infused SC at doses of either 6 or 12 mg/kg/day during the last week of pregnancy in rats. Compared with untreated controls, weight gain of dams was attenuated by DFEN without effect on the number or birth weight of offspring. Brain serotonin (5-HT) concentration and/or paroxetine binding to the 5-HT uptake carrier was reduced by 20% on the day after birth in one study but not in two other studies. No decreases in brain 5-HT parameters were observed on or after the sixth postnatal day. In contrast, mothers sustained large depletions of brain 5-HT when measured at least 3 weeks after giving birth. These data indicate that fetal brains either are protected from or recover rapidly from the 5-HT-depleting actions of high-dosage regimens of DFEN in rats.

Animals

Case report: coronary vasospasm--relation to the hyperthyroid state.

While angina is not uncommonly seen in association with hyperthyroidism, only rare case reports have suggested that myocardial ischemia in this state may be due to coronary artery spasm. The authors review the literature and describe a case in which the repetitive occurrence of episodes of myocardial ischemia due to coronary spasm correlated with repeated transient elevations in thyroid hormone levels, thus clarifying this relationship. The importance of defining thyroid status in patients presenting with coronary vasospasm is emphasized and the effects of thyroid hormone on the heart are reviewed.

Coronary Vasospasm

Sensory adaptation: extracellular recording from locust wing hinge stretch receptor.

Good student laboratory exercises that do not require much manipulative or technical expertise of the student and that have minor equipment demands are hard to find. One experiment that has these desirable characteristics is the description of adaptation of the firing frequency of the locust forewing stretch receptor after elevation of the wing. Unambiguous recordings of the activity of the stretch receptor can be made using a simple monopolar hook electrode inserted into the thoracic cavity of a decapitated locust. Elevation movements of the forewing are simple to perform and measure. The response of the stretch receptor as a function of time and the stimulus history is monitored. Within a relatively short time it is possible to collect enough data to characterize thoroughly the adequate stimulus of a single sensory neuron. There is considerable scope for student innovation, and several important concepts of sensory physiology can be discussed.

Adaptation, Physiological

Chronic hypotension. In the shadow of hypertension.

Understanding the causes and treatment of chronic hypotension is of benefit to affected patients and may also shed light on the physiology and genetics of mechanisms of blood pressure control. Symptomatic hypotension (almost always with a blood pressure fall greater than or equal to 20/10 mm Hg) may reflect unrecognized medication effects or a variety of other causes. Autonomic neuropathies include those secondary to diabetes, peripheral autonomic impairment (the Bradbury-Eggleston syndrome), central autonomic impairment (the Shy-Drager syndrome), or newly described gene defects such as dopamine-beta-hydroxylase deficiency (which causes the absence of norepinephrine with an accumulation of dopamine). Baroreceptor dysfunction causes wide swings in blood pressure that are unrelated to posture, whereas a variety of stimuli (cough, micturition, or carotid sinus pressure) may precipitate paroxysmal parasympathetic activation, and sympathetic orthostatic hypotension associated with hypovolemia may occur with mitral valve prolapse or as an idiopathic condition. The differentiation of these and other causes of symptomatic hypotension may in many cases lead to beneficial therapy.

Chronic Disease

Delayed excitatory connections in the flight system of the locust.

1. Synaptic interactions between identified neurons in the flight system of the locust were investigated by the use of standard intracellular recording and staining techniques. The intent was to determine the distribution and functional significance of delayed excitatory connections, which have been previously described. 2. For one inhibitory connection it was demonstrated that subthreshold depolarization of the presynaptic neuron was sufficient to cause release of transmitter at the synapse. This established the existence of graded interactions between spiking flight neurons. 3. Three inhibitory interneurons were found to cause delayed excitatory responses in several other neurons. Often these were coupled with direct inhibitory connections between the same pre- and postsynaptic neurons, resulting in an inhibitory/excitatory (I/E) postsynaptic potential (PSP). The two phases of this PSP were variable. 4. Delayed excitatory connections appeared powerful while the flight system was inactive. However, these connections were disabled during flight rhythms at the phase when the presynaptic neuron was depolarized and firing action potentials. This was likely to be due to the nature of the disynaptic disinhibitory interaction being via (an) intervening neuron(s) with oscillating membrane potentials and thresholds for release of transmitter. 5. Thus connections demonstrated when flight rhythms were not expressed changed their character during flight rhythms. The delayed excitatory connections in this system probably reflect complex circuits of inhibition mediated by graded interactions and have little functional significance as phenomena in their own right.

Action Potentials

Adenosine increases sympathetic nerve traffic in humans.

BACKGROUND: Adenosine is an effective hypotensive agent in experimental animals and in anesthetized patients, producing little if any evidence of reflex sympathetic activation. In contrast, adenosine increases systolic blood pressure and heart rate in conscious subjects. To determine whether this response is related to sympathetic activation, we studied the cardiovascular and respiratory effects of adenosine in normal subjects while measuring muscle sympathetic nerve traffic through direct recordings from a peroneal nerve. METHODS AND RESULTS: Adenosine (80 micrograms/kg/min i.v.) increased heart rate (+32 +/- 3 beats/min), systolic blood pressure (+10 +/- 2 mm Hg), and minute ventilation (+7 +/- 1 l/min). This was accompanied by a dose-dependent increase in muscle sympathetic nerve activity (from 198 +/- 52 to 451 +/- 92 units/min). Adenosine also produced a small, but consistent, decrease in diastolic blood pressure (-6 +/- 3 mm Hg). Adenosine produced a greater increase in sympathetic nerve traffic (145 +/- 32% above baseline) than did nitroprusside (65 +/- 16%) at doses that resulted in equivalent decreased in diastolic blood pressure. Arterial baroreceptor unloading, therefore, could not totally explain the increase in sympathetic traffic produced by adenosine. CONCLUSIONS: Given the constellation of findings of increased ventilation and sympathetic activity, we, therefore, propose that adenosine increases sympathetic tone by activating afferent nerves, including arterial chemoreceptors. Contrary to the known inhibitory actions of adenosine on central and peripheral efferent systems, this and other reports suggest that adenosine-induced activation of afferent nerves, leading to sympathetic activation, may be a more widespread phenomenon than previously recognized.

Adenosine

Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation.

Dopamine beta-hydroxylase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.

Adult

Effects of caffeine on baroreflex activity in humans.

The effects of caffeine or placebo on blood pressure, heart rate, and baroreflex activation (elicited by phenylephrine) were studied on young normotensive volunteers after a 7-day caffeine-free period. Subjects received oral doses of either 250 mg caffeine (n = 6) or placebo (n = 4), and hemodynamic changes were studied at 0, 30, 60, 120, and 180 minutes after drug administration. Thirty minutes after the caffeine dose, blood pressure had risen from 127 +/- 8/57 +/- 4 mm Hg to 136 +/- 3/68 +/- 5 mm Hg, heart rate was unchanged, and the baroreflex slope had decreased from 31 +/- 7 msec/mm Hg to 11.6 +/- 2 msec/mm Hg. Baroreflex sensitivity remained inhibited for the rest of the single-dose experimental period. In contrast, no significant changes were observed after either long-term caffeine ingestion in the same group or in the placebo group during the single- or multiple-dose study. These findings indicate that single but not multiple caffeine administration inhibits baroreflex activation in normotensive volunteers and this could contribute to the acute hemodynamic effects of caffeine.

Administration, Oral

Reflex control of sympathetic nerve activity in dopamine beta-hydroxylase deficiency.

Patients with autonomic failure secondary to dopamine beta-hydroxylase deficiency lack the enzyme activity necessary for the conversion of dopamine to norepinephrine in sympathetic nerve terminals and the adrenal medulla. These patients have virtually undetectable norepinephrine and epinephrine in plasma and cerebrospinal fluid. The presence of intact sympathetic nerve activity in these patients has been suggested by the enhanced release of dopamine (but not norepinephrine) in response to maneuvers that augment sympathetic outflow in normal subjects. In the present study, we recorded sympathetic nerve traffic by using microneurography in a patient with dopamine beta-hydroxylase deficiency and measured sympathetic neural responses to static exercise, the cold pressor test, and pharmacological alterations of blood pressure. At rest, sympathetic nerve activity was abundant and was modulated in a normal manner by handgrip (+278%), the cold pressor test (+169%), hypotension induced with isoproterenol (+102%), and hypertension induced with phenylephrine (-85%). These results provide the first electrophysiological evidence for intact regulation of sympathetic neural outflow in a patient with dopamine beta-hydroxylase deficiency and suggest that central norepinephrine and epinephrine pathways believed essential for the control of sympathetic neurotransmission in humans may be supplanted by alternative redundant mechanisms.

Adult

Morphological study of flight motor neurons in the cricket.

The motor innervation of the major flight muscles powering the fore- and hindwings of the cricket Teleogryllus oceanicus was investigated. The morphology of the motor neurons was determined by filling them via their axons in the periphery with either Lucifer Yellow or cobalt chloride followed by silver intensification. Details of the location of branches of motor neurons within the ganglion were obtained by serially sectioning ganglia containing filled neurons. For each flight muscle at least two motor neurons were found. The somata of motor neurons were located in two clusters in the ganglion, the anterior lateral cluster and the posterior lateral cluster. Motor neurons in the same cluster had similar morphologies. Most of the arborizations of these motor neurons were in the dorsal neuropil with a few branches in the lateral intermediate neuropil. The morphology of flight motor neurons was compared with the morphology of leg motor neurons in consideration of the possible functional organization of the ganglion. A comparison was made between motor neurons innervating homologous muscles of the cricket and the locust to determine the extent of the difference between the flight systems of these two groups.

Animals

Management of chronic orthostatic hypotension.

Chronic orthostatic hypotension is characterized by recurrent symptoms of cerebral hypoperfusion due to low upright blood pressure levels. The initial approach should be to identify and correct reversible causes. Persistence of orthostatic hypotension suggests autonomic failure. The goal of management is to minimize symptoms and maximize functional capacity; therefore the magnitude of blood pressure fall is not as important as the advent of symptoms. Therapy is based upon the underlying pathophysiology and the risk/benefit ratio of interventions. Patient education and nondrug measures form the cornerstone of management. Drug therapy is often limited by unacceptable supine hypertension. Rational drug use can be governed by individualized trials of therapy. Patients with moderate or severe orthostatic hypotension are difficult to treat, but can be helped toward resumption of a normal life.

Activities of Daily Living

The structure and function of the labrum in the lobster Homarus gammarus (L.).

The labrum of decapod crustaceans is a soft lobe overhanging the mouth. The labral skeleton, musculature and innervation of Homarus gammarus are described. There are three bilateral groups of sensory neurons innervating the floor, lobe and lateral walls of the labrum. These are probably responsible for the phasic afferent activity that can be recorded from the inner labral nerve on mechanical deformation of the labrum. The labrum undergoes rhythmical retraction-protraction movements during ingestion and is shown to be active during both mandibular activity and oesophageal peristalsis. Studies were made on the duration and frequency of labral "swallowing" activity. The role of the labrum in feeding is discussed.

Animals

Oesophageal sensors and their modulatory influence on oesophageal peristalsis in the lobster, Homarus gammarus.

The musculature and innervation of the oesophagus of Homarus gammarus are described as a prerequisite to studies on the mechanisms and control of food ingestion. Of particular interest are two paired sensors (the anterior and posterior oesophageal sensors) which are bilaterally situated at the oesophageal-cardiac sac valve. These are similar to contact chemoreceptors previously described in insects and are classified as such on morphological grounds and with indirect electrophysiological evidence. Oesophageal peristalsis is effected by the coordinated contraction of the Oesophageal musculature. This is controlled by rhythmical bursting neuronal activity, which can be recorded from the nerve trunks in the area. A characteristic burst recorded from the superior oesophageal nerve is used as an indication of oesophageal dilatation during peristalsis for studies on the feedback effects of the oesophageal sensors. Electrical and chemical stimulation of the posterior oesophageal sensors can initiate and increase the frequency of oesophageal peristalsis, while stimulation of the anterior oesophageal sensors can slow and terminate oesophageal peristalsis. The results are discussed and a model presented of the role of the oesophageal sensors in feeding.

Animals

Variant angina pectoris: investigation of indexes of sympathetic nervous system function.

One thousand forty-five spontaneous episodes of S-T segment elevation were observed in three patients over a total of 72 days of continuous electrocardiographic monitoring. Eighty-nine percent of episodes were asymptomatic; chest pain tended to occur with episodes longer than 3 minutes, and ventricular ectopy occurred almost exclusively with symptomatic episodes. Nitroglycerin regularly relieved angina or S-T elevation, or both. Plasma and urinary catecholamines and their metabolites were normal. Episodes of variant angina were not associated with a generalized increase in sympathetic outflow because serum catecholamine levels at the onset and termination of the S-T abnormalities were not elevated. Controlled trials of propranolol showed no significant beneficial effect. Propranolol significantly increased the length of episodes of S-T elevation in one patient, increasing ventricular irritability. The overall course of variant angina was quite variable, with spontaneous and long-lasting remissions, necessitating cautions interpretation of clinical trials.

Angina Pectoris