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Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control.

Power spectrum analysis of heart rate fluctuations provides a quantitative noninvasive means of assessing the functioning of the short-term cardiovascular control systems. We show that sympathetic and parasympathetic nervous activity make frequency-specific contributions to the heart rate power spectrum, and that renin-angiotensin system activity strongly modulates the amplitude of the spectral peak located at 0.04 hertz. Our data therefore provide evidence that the renin-angiotensin system plays a significant role in short-term cardiovascular control in the time scale of seconds to minutes.

Angiotensins↗

Novel consent process for research in dying patients unable to give consent.

OBJECTIVES: To develop a process of advance consent to enable research to be undertaken in patients in the terminal phase. DESIGN: Feasibility study of an advance consent process to support a randomised controlled trial of two antimuscarinic drugs (hyoscine hydrobromide and glycopyrronium bromide) in the management of noisy respirations associated with retained secretions ("death rattle"). SETTING: Palliative care wards in a major cancer centre. PARTICIPANTS: Patients admitted to a palliative care ward who may develop "death rattle" and thus be eligible for randomisation. MAIN OUTCOME MEASURES: Patient accrual; acceptability of the consent process. RESULTS: Of the 107 patients approached, 58 patients gave advance consent to participate in the study. Of these, 15 patients developed death rattle and were randomised to receive either hyoscine or glycopyrronium; 16 patients died elsewhere; 15 patients died on the palliative care wards but were not randomised; 12 patients are still alive. CONCLUSIONS: Initial assessment suggests that this is a workable consent process allowing research to be undertaken in patients who are unable to give consent at the time of randomisation. Patient accrual rates to date are lower than needed to recruit adequate numbers in the time allotted to answer the research question.

Advance Directives↗

A controlled trial of glycopyrronium and l-hyoscyamine in the long-term treatment of duodenal ulcer.

A controlled single-blind trial has been carried out to determine the value of long-term anticholinergic therapy in duodenal ulcer. Of 106 male patients with symptomatic and radiologically proven duodenal ulcer admitted to the trial, 91 completed the study. Patients were divided randomly into three groups. They received either glycopyrronium, or 1-hyoscyamine in a sustained-release form, or inert tablets for one year. Progress was judged on the basis of frequency and severity of symptoms, monthly assessments by patients, antacid consumption, and radiology. By all criteria, glycopyrronium and 1-hyoscyamine were not significantly superior to placebo. Symptomatic improvement, both subjective and objective, occurred in approximately 80% of all patients during the year of observation; there was no significant difference between the groups.

Adult↗

Central and peripheral effects of arecoline in patients with autonomic failure.

Increased plasma adrenalin (A) levels following arecoline in normal subjects and patients with multiple system atrophy (MSA) may result from nicotinic adrenal stimulation. Lack of this response in patients with pure autonomic failure (PAF) is consistent with peripheral sympathetic dysfunction. The mechanisms underlying diminished plasma corticotropin (ACTH) responses to arecoline may differ in patients with autonomic failure. Hypothalamic, cholinergic degeneration could prevent the response in MSA whereas patients with PAF do not manifest the normal increase in A which may be required to elicit an ACTH response. The appearance and exacerbation of tremor, vertigo, and pathological affect in the MSA group suggest that some central cholinergic receptors remain functional.

Adrenocorticotropic Hormone↗

Heart rate dynamics in monoamine oxidase-A- and -B-deficient mice.

Heart rate (HR) dynamics were investigated in mice deficient in monoamine oxidase A and B, whose phenotype includes elevated tissue levels of norepinephrine, serotonin, dopamine, and phenylethylamine. In their home cages, spectral analysis of R-R intervals revealed more pronounced fluctuations at all frequencies in the mutants compared with wild-type controls, with a particular enhancement at 1-4 Hz. No significant genotypic differences in HR variability (HRV) or entropies calculated from Poincaré plots of the R-R intervals were noted. During exposure to the stress of a novel environment, HR increased and HRV decreased in both genotypes. However, mutants, unlike controls, demonstrated a rapid return to baseline HR during the 10-min exposure. Such modulation may result from an enhanced vagal tone, as suggested by the observation that mutants responded to cholinergic blockade with a decrease in HRV and a prolonged tachycardia greater than controls. Monoamine oxidase-deficient mice may represent a useful experimental model for studying compensatory mechanisms responsible for changes in HR dynamics in chronic states of high sympathetic tone.

Animals↗

Hemodynamic regulation: investigation by spectral analysis.

We investigated the hypothesis that beat-to-beat variability in hemodynamic parameters reflects the dynamic interplay between ongoing perturbations to circulatory function and the compensatory response of short-term cardiovascular control systems. Spontaneous fluctuations in heart rate (HR), arterial blood pressure, and respiration were analyzed by spectral analysis in the 0.02- to 1-Hz frequency range. A simple closed-loop model of short-term cardiovascular control was proposed and evaluated in a series of experiments: pharmacological blockades of the parasympathetic, alpha-sympathetic, beta-sympathetic, and renin-angiotensin systems were used to open the principal control loops in order to examine changes in the spectral pattern of the fluctuations. Atrial pacing was used to examine blood pressure variability in the absence of HR variability. We found that respiratory frequency fluctuations in HR are parasympathetically mediated and that blood pressure fluctuations at this frequency result almost entirely from the direct effect of centrally mediated HR fluctuations. The sympathetic nervous system appears to be too sluggish to mediate respiratory frequency variations. Low-frequency (0.02-0.09 Hz) fluctuations in HR are jointly mediated by the parasympathetic and beta-sympathetic systems and appear to compensate for blood pressure fluctuations at this frequency. Low-frequency blood pressure fluctuations are probably due to variability in vasomotor activity which is normally damped by renin-angiotensin system activity. Blockade of the alpha-adrenergic system, however, does not significantly alter low-frequency blood pressure fluctuations.

Animals↗

Hygrophotographic technique for testing local antiperspirant activity.

Bilateral stopping of plantar perspiration in the mouse was obtained by application of a cotton-wool swab soaked in a 3% solution of BRL 556 in 60% ethanol for 1--2 min to the plantar surface of its right hind paw. For humans, aerosols which are at present on the market produce a sensible reduction in palmar sweating. The effect was recorded and illustrated by a modified hygrophotographic technique in which the sweat, released in the form of water vapor, was recorded by the hygrophotographic film, without any contact with the skin. In the mouse, the recording was carried out by the application to the plantar surface of a piece of hygrophotographic film, by the aid of an adhesive tape.

Administration, Topical↗

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling associated with chronic reduction in beta-adrenergic receptor agonist activation were found. First, there was coordinate downregulation of Gi alpha 2 and Gs alpha mRNA and protein expression in the left ventricle; reduced G-protein content was also found in the right atrium. Second, in the left ventricle, there was a twofold increase in beta-adrenergic receptor-dependent stimulation of adenylyl cyclase and a persistent high affinity state of the beta-adrenergic receptor. Finally, there was a reduction in left ventricular beta-adrenergic receptor kinase activity, suggesting a previously unrecognized association between the degree of adrenergic activation and myocardial beta-adrenergic receptor kinase expression. The heart appears to adapt in response to chronic beta-adrenergic receptor antagonist administration in a manner that would be expected to offset reduced agonist stimulation. The mechanisms for achieving this extend beyond beta-adrenergic receptor upregulation and include alterations in G-protein expression, beta-adrenergic receptor-Gs interaction, and myocardial beta-adrenergic receptor kinase activity.

Adaptation, Biological↗

Hyoscine vs glycopyrronium for drying respiratory secretions in dying patients.

The 'death rattle' is a common symptom among dying people, and causes a great deal of anxiety and upset to relatives and carers, including nurses. A mini-review was carried out to evaluate the effectiveness of two drugs--hyoscine hydrobromide and glycopyrronium--in drying up respiratory secretions in terminally ill patients. Searches were made of the Cochrane Library, Medline, Embase, Cinahl and Pharmline. Reference lists, trial databases and professional colleagues were also consulted. There was a scarcity of research material directly comparing the effects of the two drugs in the clinical setting. Two papers were used for comparison in the review but these produced conflicting results. Many discrepancies existed in terms of research methods, and in results. One paper demonstrated that hyoscine hydrobromide was the more effective drug; the other favoured glycopyrronium. There is no clear evidence to support the choice of one drug over the other, based on the clinical outcome selected for this review. Although clinical trials are difficult to conduct in this vulnerable patient group, more research is needed to facilitate the best management of this distressing symptom and allow clinical guidelines to be produced.

Dose-Response Relationship, Drug↗

Sialorrhea.

Explore the source record for details and available documents.

Cholinergic Antagonists↗

Controlling sialorrhoea: a review of available treatment options.

Sialorrhoea (drooling or excessive salivation) is a common symptom of many neurological diseases (e.g., amyotropic lateral sclerosis, cerebral palsy and Parkinson's disease) and otolaryngologic diseases (tumours of upper aerodigestive tract). It is mostly caused by poor oral and facial muscle control in patients with swallowing dysfunction (secondary sialorrhoea). However, some cases of sialorrhoea are due to hypersecretion of saliva. These cases represent so-called primary sialorrhoea.

Botulinum Toxins, Type A↗