In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at approximately 0.25 Hz and a low frequency at approximately 0.1 Hz, with a normalized low frequency:high frequency ratio of 3.6 +/- 0.7. With tilt, the low-frequency component became largely predominant (90 +/- 1%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency:high frequency ratio induced by tilt. Chronic beta-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency:high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency:high frequency ratio (0.7 +/- 0.1); during tilt, the increase in the low frequency:high frequency ratio (8.3 +/- 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency:high frequency ratio at rest of 2.8 +/- 0.7, which became 17 +/- 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation.(ABSTRACT TRUNCATED AT 400 WORDS)

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Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1469-8986.1997.tb02140.x

Heart rate variability: Origins, methods, and interpretive caveats

Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.

The inflammatory reflex

BACKGROUNDWe studied 715 patients 2 weeks after myocardial infarction to establish the associations between six frequency domain measures of heart period variability (HPV) and mortality during 4 ye...

Frequency domain measures of heart period variability and mortality after myocardial infarction.

This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.

Arterial baroreceptor reflex: its central and peripheral neural mechanisms.

1. In the guinea pig, the central projections of somatic and visceral C-afferent fibers were compared by tracing arborizations labeled through injection of Phaseolus vulgaris leucoagglutinin (PHA-L) intracellularly into single neurons of the 13th thoracic dorsal root ganglia (DRG). 2. Two of 27 somatic C-afferent neurons that responded to electrical stimulation of the 13th thoracic (subcostal) nerve (conduction velocity: 0.69 +/- 0.14 m/s, mean +/- SD) were well enough marked to allow delineation of their central processes. In both cases, the entering axon ran rostrally, giving off branches that converged on a single terminal field located in the substantia gelatinosa (lamina II) with some extension in lamina I. The terminal field in each case extended approximately 400 microns rostrocaudally and 100 microns mediolaterally. 3. Intracellular recordings were obtained from 31 afferent units that responded to electrical stimulation of the celiac ganglion. Units with onset latencies of greater than 15 ms were classified as having visceral C-afferent fibers because the shortest course from the celiac ganglion stimulation electrodes to the DRG was greater than 7 mm (i.e., a conduction velocity of less than 0.5 m/s). 4. Seven visceral C-afferent fibers were labeled well enough to follow their central trajectories. Each had a main ascending and a descending central branch. Each main branch in turn issued several collaterals that terminated in the superficial dorsal horn (laminae I and II), laminae IV, V, and X, and occasionally in the dorsal and lateral funiculi. A few collaterals reached the contralateral laminae V and X.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers

Beat-to-beat changes observed in cardiac vagal and sympathetic nerve activity and their effects on cardiac cycle length were studied during slow wave blood pressure and heart rate fluctuations (third order rhythm) and during respiratory sinus arrhythmia. Recordings were made from both nerves simultaneously in chloralose anesthetized and artificially ventilated dogs. During slow wave fluctuations in heart rate, a linear relationship was found to exist between the number of spikes per pulse interval recorded from vagal and sympathetic nerves and the length of pulse intervals. During respiratory sinus arrhythmia the time course of rhythmic changes in nerve activity and in cardiac cycle length was analyzed. Comparison of time courses indicated that vagal discharges affected the timing of not the following beat, but the one after; while the sympathetic effect was further delayed, affecting the third beat after the discharge. Baroreceptor stimulation, which resulted in lengthening the cardiac cycle, shifted this relationship by one cycle, i.e. vagal discharges affecting the occurrence of the following beat, while sympathetic discharges affecting the beat after. These results provide evidence for the conclusion that in dogs both vagal and symphathetic nerve activity contribute to the control of cardiac cycle length, however, with different time relations and effectiveness.

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations.

In 55 anesthetized and paralyzed adult rabbits, 161 spontaneously active neurons which responded to electrical stimulation of A-fibers of the aortic nerve were found within the ventrolateral medulla (VLM). They were termed barosensory VLM neurons, since the aortic nerve A-fibers were considered to consist exclusively of afferents from arterial baroreceptors. Forty percent of barosensory VLM neurons tested (49/123) were activated antidromically by stimulation of the dorsolateral funiculus indicating that they send descending bulbospinal projections. Spontaneous discharges of barosensory VLM neurons were invariably inhibited by stimulation of aortic nerve A-fibers. Ninety-three percent of 80 neurons tested also responded to stimulation of aortic nerve C-fibers, a mixture of barosensory and nonbarosensory afferents. Natural stimulation of carotid sinus baroreceptors by an intravenous injection of phenylephrine in 19 vagotomized rabbits with aortic nerves disrupted inhibited spontaneous activity of all the 50 barosensory VLM neurons tested. By contrast, pharmacological stimulation of right or left carotid body chemoreceptors by close arterial injection of NaCN into the carotid sinus augmented activity of 93% of barosensory VLM neurons tested (41/44). The neuronal response was always greater to stimulation of chemoreceptors in the contralateral carotid sinus. Seven out of 8 barosensory VLM neurons tested (88%) were orthodromically excited by stimulation of the posterior hypothalamic area. In 74% of the 97 neurons examined in 29 vagotomized animals, a distinct respiratory-related rhythm, locked to that of phrenic nerve activity, was discerned. Thus, spontaneous activity of barosensory VLM neurons is inhibited by afferent inputs from aortic and carotid sinus baroreceptors, but is excited by incoming signals from carotid body chemoreceptors and the posterior hypothalamic area. It is also subject to the influence of the central mechanism generating the respiratory rhythm.

Barosensory neurons in the ventrolateral medulla in rabbits and their responses to various afferent inputs from peripheral and central sources.

Simultaneous recording of activity in the vagal and sympathetic supplies to the heart has revealed that in reflexly and centrally evoked activity these two "antagonists" do not necessarily change action reciprocally. Coactivation occurs in chemoreceptor reflexes and related reactions, upon stretching of the sinoatrial nodal region of the right atrium and when certain hypothalamic regions are stimulated. The objective of the present work was to assay the physiological importance of coactivation of the two potentially antagonistic cardiac nerves in anesthetized dogs. Output from the heart was monitored by recording volume flow in the thoracic aorta just below the aortic arch; cardiac contractility was measured as left ventricular dp/dt. Tape recordings of vagus and sympathetic nerve activity during chemoreceptor and baroreceptor reflexes, during reciprocal and nonreciprocal changes produced by hypothalamic stimulation, and during hypoxia and hypercapnia were used to trigger stimulators feeding a stimulus per action potential to cardiac vagus and sympathetic nerves after central connections were cut. The vagus stimulation alone produced a decrease in aortic blood flow; stimulation of the sympathetic nerve alone resulted in increased aortic blood flow. Simultaneous stimulation of vagus and sympathetic, however, produced an even greater cardiac output (measured by aortic blood flow). Intermediate degrees of heart rate and strength of myocardial contraction were maintained in coactivation. Obviously, an association of increased vagus and sympathetic actions, which can be effected reflexly or by action of higher centers, is of physiological benefit. In control reactions that relate cardiac function to body need, both reciprocal and synergistic actions (coactivation) of cardiac nerves are used.

https://www.pnas.org/content/pnas/79/6/2116.full.pdf

Naohito Terui

Papers

Arterial baroreceptor reflex: its central and peripheral neural mechanisms.

Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations.

Barosensory neurons in the ventrolateral medulla in rabbits and their responses to various afferent inputs from peripheral and central sources.

Functional significance of coactivation of vagal and sympathetic cardiac nerves