Decreased physiologic variability as a generalized response to human endotoxemia*

Rassias, Athos J.; Holzberger, Peter T.; Givan, Alice L.; Fahrner, Scott L.; Yeager, Mark P.

doi:10.1097/01.ccm.0000155908.46346.ed

Cited by 55 publications

(34 citation statements)

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“…Elective administration of endotoxin to otherwise healthy human volunteers has been used to study systemic inflammation and gain insight into behavior of inflammatory mediators encountered in acute, as well as chronic, inflammatory disease. Human endotoxemia precipitates signs and symptoms characteristic of clinical sepsis (6,48) and ARDS (15), inducing a reduction in HRV (28,65). While we do not argue that the human endotoxin (LPS) challenge model precisely replicates an acute infectious or sepsis condition, human endotoxin challenge does serve as a useful model of Toll-like receptor 4 (TLR4) agonist-induced systemic inflammation by providing a reproducible experimental platform tying systemic inflammation to physiological signal generation and alterations in HRV.…”

Section: Methodsmentioning

confidence: 99%

“…Responses observed in human endotoxemia experiments mimic observed responses in systemic inflammation in ICU patients, albeit over different timescales (30), thus making the human endotoxemia model an excellent platform for exploring mechanistic underpinnings of the systemic inflammatory response. A key component in the response to endotoxemia is a decrease in HRV, concomitant with imbalances in autonomic activity reflected by perturbed autonomic oscillatory responses in heart rate (HR) (28,35,36,65).Despite an understanding of the importance of inflammation in a wide variety of disorders and a large number of experiments elucidating the details of the inflammatory response, novel treatments aimed at controlling inflammation remain elusive (25). The complexity of the interacting, redundant pathways involved in the inflammatory response necessitates a systems-level understanding of inflammation (72,80), thus leading to interest in the inflammatory response from a systems biology perspective (79).…”

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Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia

Scheff¹,

Mavroudis

Calvano

et al. 2011

Physiological Genomics

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Scheff JD, Mavroudis PD, Calvano SE, Lowry SF, Androulakis IP. Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia. Physiol Genomics 43: 951-964, 2011. First published June 14, 2011 doi:10.1152/physiolgenomics.00040.2011.-Heart rate variability (HRV), the quantification of beat-to-beat variability, has been studied as a potential prognostic marker in inflammatory diseases such as sepsis. HRV normally reflects significant levels of variability in homeostasis, which can be lost under stress. Much effort has been placed in interpreting HRV from the perspective of quantitatively understanding how stressors alter HRV dynamics, but the molecular and cellular mechanisms that give rise to both homeostatic HRV and changes in HRV have received less focus. Here, we develop a mathematical model of human endotoxemia that incorporates the oscillatory signals giving rise to HRV and their signal transduction to the heart. Connections between processes at the cellular, molecular, and neural levels are quantitatively linked to HRV. Rhythmic signals representing autonomic oscillations and circadian rhythms converge to modulate the pattern of heartbeats, and the effects of these oscillators are diminished in the acute endotoxemia response. Based on the semimechanistic model developed herein, homeostatic and acute stress responses of HRV are studied in terms of these oscillatory signals. Understanding the loss of HRV in endotoxemia serves as a step toward understanding changes in HRV observed clinically through translational applications of systems biology based on the relationship between biological processes and clinical outcomes. systems biology; inflammation; circadian HEART RATE VARIABILITY (HRV) is generally defined as the quantification of the distribution of time intervals between successive heartbeats. Reduction in HRV, a manifestation of altered autonomic function under stress, is potentially a useful predictor of outcome in myocardial infarction (42), congestive heart failure (63), diabetic neuropathy (58), and neonatal sepsis (46). Diminished HRV has also been observed in critically ill patients in intensive care units (ICU) (52), which motivates interest in HRV as a critical variable in the recovery from critical illness (50). Due to this clinical relevance, dynamic characteristics of HRV have been assessed by time domain, frequency domain (76), and nonlinear metrics (46, 60). The majority of HRV research has thus far focused on the interpretation of the patterns of HRV (45) rather than linking cellular-level mechanisms to patterns (11). The realization that health may be characterized by a certain degree of variability of human heart signals motivates the hypothesis that appropriate physiological variability is the manifestation of robust dynamics of control signals whose fluctuations equip the host with the ability to anticipate external and internal disturbances. We hypothesize that these variable dynamics are driven by the convergence of rhythmic physiological signals on...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia

Scheff¹,

Mavroudis

Calvano

et al. 2011

Physiological Genomics

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“…Loss of cardiac complexity has also been shown to be associated with inflammation and cardiovascular disease burden (37,48). Lifestyle modification in the form of dietary alteration and exercise is currently recommended as a means of primary cardiovascular disease prevention in African Americans (12).…”

Section: Perspectives and Significancementioning

confidence: 99%

C-reactive protein and cardiac vagal activity following resistance exercise training in young African-American and white men

Heffernan¹,

Jae²,

Vieira³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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B. C-reactive protein and cardiac vagal activity following resistance exercise training in young African-American and white men. Am J Physiol Regul Integr Comp Physiol 296: R1098-R1105, 2009. First published February 4, 2009 doi:10.1152 doi:10. /ajpregu.90936.2008 Americans have a greater prevalence of hypertension and diabetes compared with white Americans, and both autonomic dysregulation and inflammation have been implicated in the etiology of these disease states. The purpose of this study was to examine the cardiac autonomic and systemic inflammatory response to resistance training in young African-American and white men. Linear (time and frequency domain) and nonlinear (sample entropy) heart rate variability, baroreflex sensitivity, tonic and reflex vagal activity, and postexercise heart rate recovery were used to assess cardiac vagal modulation. C-reactive protein (CRP) and white blood cell count were used as inflammatory markers. Twenty two white and 19 African-American men completed 6 wk of resistance training followed by 4 wk of exercise detraining (Post 2). Sample entropy, tonic and reflex vagal activity, and heart rate recovery were increased in white and African-American men following resistance training (P Ͻ 0.05). Following detraining (Post 2), sample entropy, tonic and reflex vagal activity, and heart rate recovery returned to baseline values in white men but remained above baseline in African-American men. While there were no changes in white blood cell count or CRP in white men, these inflammatory markers decreased in African-American men following resistance training, with reductions being maintained following detraining (P Ͻ 0.05). In conclusion, resistance training improves cardiac autonomic function and reduces inflammation in African-American men, and these adaptations remained after the cessation of training. Resistance training may be an important lifestyle modification for improving cardiac autonomic health and reducing inflammation in young African-American men.heart rate variability; exercise; heart rate recovery; inflammation

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“…Decreased HRV is consistent with the pathogenesis of MODS, which involves the physiological uncoupling of vital organ systems. In fact, HRV decreases in response to human endotoxemia Rassias et al, 2005), and is a good index of cardiac mortality (Schmidt et al, 2001). Moreover, patients with sepsis (Barnaby et al, 2002) and MODS (Korach et al, 2001;Schmidt et al, 2005) have an impaired sympatho-vagal balance.…”

Section: Pathophysiology Of Sepsis and Multiple Organ Dysfunction Synmentioning

confidence: 99%

Neural Reflex Control of Inflammation During Sepsis Syndromes

Fernández¹,

Acuña-Castillo²

2012

Sepsis - An Ongoing and Significant Challenge

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Decreased physiologic variability as a generalized response to human endotoxemia*

Abstract: Increased regularity, or decreased variability, of organ functions is a generalized response to systemic inflammation that occurs in widely divergent systems during endotoxemia.

Cited by 55 publications

References 55 publications

Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia

Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia

C-reactive protein and cardiac vagal activity following resistance exercise training in young African-American and white men

Neural Reflex Control of Inflammation During Sepsis Syndromes

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