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Biomedical subjects

R M Robertson

Publications and source records attributed to R M Robertson.

At least 73 records · Page 4Linked to original sources

Orthostatic hypotension of prolonged weightlessness: clinical models.

Orthostatic intolerance on return from space is a widely known consequence of space travel. Development of countermeasures against this problem is a major priority of the field of space physiology and medicine. The bedrest model is widely used in the investigation of this phenomenon, and has provided important data, but questions remain. In this article, we suggest that the disorders that produce chronic orthostatic hypotension have significant potential as models of microgravity-induced orthostatic intolerance. Understanding the pathophysiology of these syndromes may be useful to those involved in improving the operational aspects of manned space flight; four such syndromes and their possible relevance to space flight are described.

Autonomic Nervous System Diseases↗

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↗

Neuropeptide Y is a vasoconstrictor of human coronary arteries.

Neuropeptide Y (NPY) is a 36-amino-acid polypeptide which coexists with catecholamines in many adrenergic and noradrenergic neurons. It has been demonstrated to exert pressor effects in the perfused guinea pig heart and to constrict large cerebral and coronary blood vessels in animal studies. To determine if NPY might be a human coronary vasoconstrictor, the authors studied its effect on postmortem human coronary arteries. Proximal epicardial coronary rings were studied in a superfusion apparatus in Krebs-Ringer bicarbonate buffer (37 degrees C, pH 7.4) presaturated with 95% O2-5% CO2. Concentration-response curves were obtained using NPY in 0.1% bovine serum albumin in buffer and the responses were compared to those obtained in the presence of alpha 1, beta, and cyclooxygenase antagonists. A dose-related constrictor effect was obtained with NPY, which was significantly more potent than noradrenaline, constriction often being seen at 10(-12) M concentration. A vasorelaxant effect was seen in nonatherosclerotic vessels at higher concentrations. The vasoconstriction produced by noradrenaline was potentiated by subthreshold concentrations of NPY. The vasoconstrictor effect of NPY was not inhibited by prazosin (10(-6) M), and the vasodilatory effect was not inhibited by propranolol (10(-5) M). Indomethacin (3 X 10(-6) M) did not alter either vasoconstriction or vasorelaxation. The authors conclude that NPY is a potent constrictor of the human coronary artery at concentrations that may be achievable in vivo; it may thus be a contributor to sympathetic enhancement of coronary artery tone.

Coronary Vessels↗

A local circuit interaction in the flight system of the locust.

Most of the interneurons that have been identified in the locust flight system to date are spiking, intersegmental interneurons and the described interactions between them are spike-mediated postsynaptic potentials. We wished to discover whether the same interneurons also communicate via subthreshold interactions to form local circuits independent of their spike-mediated connections. Using a deafferented flight preparation of the locust and glass microelectrodes, we recorded simultaneously from the neuropil segments of different interneurons within a single thoracic ganglion. Interneuron 301 had an indirect connection with the contralateral 301 and an indirect connection feeding back to itself. The feedback circuit could be activated with subthreshold stimuli. Spikes in a 301 affected self and contralateral partner, whereas subthreshold stimuli affected only self. Thus, this paper demonstrates the existence of 2 pathways from a single interneuron that can be functionally separate depending on whether activity in the interneuron is subthreshold or suprathreshold for spiking. The results show that dendritic regions of spiking intersegmental interneurons in the locust can participate in local circuits whose operation could have a considerable role to play in neural integration.

Action Potentials↗

Cardiovascular and respiratory effects of adenosine in conscious man. Evidence for chemoreceptor activation.

The cardiovascular and respiratory effects of intravenous adenosine were studied in conscious normal volunteers. Bolus injections of adenosine increased systolic and diastolic pressures initially (+15 and +13 mm Hg after 100 micrograms/kg) followed by a subsequent reduction in systolic and diastolic pressures (-12 and -16 mm Hg). Heart rate increased during trough blood pressure (R-R interval shortening of 298 msec after 100 micrograms/kg). Adenosine steady-state infusions increased heart rate (+30 beats/min during 140 micrograms/kg/min), systolic pressure (+16 mm Hg), and pulse pressure (+21 mm Hg) but decreased diastolic pressure slightly (-5 mm Hg), resulting in no significant change in mean arterial pressure. Adenosine stimulated respiration, resulting in decreased PaCO2 (41 to 31 mm Hg), increased PaCO2 (101 to 113 mm Hg), and increased pH (7.42 to 7.50). The increased ventilation was not explained by bronchoconstriction, hypotension, or hypoxia. The observed pressor and tachycardic effects are mediated through reflex autonomic mechanisms since they are completely abolished in patients with severe autonomic failure. These autonomic mechanisms probably involve chemoreceptor activation since adenosine is pressor when infused in the aortic arch proximal to the origin of the carotid arteries but depressor when infused in the descending aorta. It is concluded that the hemodynamic and respiratory effects of adenosine observed in normal volunteers are in part due to chemoreceptor stimulation. These findings raise the possibility that adenosine is an endogenous modulator of respiration in man.

Adenosine↗

Electrocardiographic markers of cardiac metastasis.

Cardiac metastases are often clinically inapparent but have important prognostic significance. A total of 1046 consecutive autopsies performed between 1981 and 1983 were reviewed, and 210 patients with both premortem and autopsy diagnoses of cancer were found, in whom a recent (less than 3 months before death) ECG was available. Of these patients, 47 had cardiac metastases (group I) and 163 did not (group II). In group I, 19 patients had new ECG changes suggestive of myocardial ischemia or injury, including either diffuse T wave inversion (10%), segmental (ECG pattern suggestive of a specific coronary distribution) T wave inversion (80%), or ST elevation (10%). None of these patients had symptoms suggestive of myocardial ischemia. In group II, six patients had ECG changes suggestive of myocardial ischemia or injury: four patients with preterminal sepsis, one with myocardial infarction, and one with aspergillus nodules within the myocardium. New atrial arrhythmias (seven patients) and low voltage (10 patients) were found with greater frequency in group I patients (p less than 0.0005 and p less than 0.00001, respectively, vs group II). Patients with normal ECGs were unlikely to have cardiac metastases; however, the finding of nonspecific ST-T wave changes was not helpful in differentiating the two groups. In clinically stable patients with cancer and no cardiac symptoms suggestive of ischemia, any new ECG change should raise the suspicion of cardiac metastases. The ECG finding of myocardial ischemia or injury has high specificity (96%, p less than 0.000001) for cardiac metastases.

Adolescent↗