Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations

Vasilios Papaioannou, Ioannis Pneumatikos, Nikos Maglaveras, Vasilios Papaioannou, Ioannis Pneumatikos, Nikos Maglaveras

Abstract

Many experimental and clinical studies have confirmed a continuous cross-talk between both sympathetic and parasympathetic branches of autonomic nervous system and inflammatory response, in different clinical scenarios. In cardiovascular diseases, inflammation has been proven to play a pivotal role in disease progression, pathogenesis and resolution. A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals' processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers. However, a lot of open questions remain to be addressed, regarding the existence of a true association between heart rate variability and autonomic nervous system output or its adoption for risk stratification and therapeutic monitoring at the bedside. Finally, potential therapeutic implications will be discussed, leading to autonomic balance restoration in relation with inflammatory control.

Keywords: autonomic nervous system; cardiovascular disease; coronary artery disease; heart rate variability; inflammation; mortality.

Figures

Figure 1
Figure 1
(A) Longitudinal trends over time of mean values of CRP and LF/HF ratio, reflecting sympathovagal balance, for patients with SOFA > 10, during the 6 days of study period. [log transformed data, adapted from Papaioannou et al. (2009)]. It appears that LF/HF changes inversely with CRP. (B) Longitudinal trends over time of mean values of CRP and SDNN (secs), for patients with SOFA > 10, during the 6 days of study period. [log transformed data, adapted from Papaioannou et al. (2009)]. There is a progressive increase in SOFA score from day 1 until day 4 (development of septic shock) and a subsequent downward shift in its values. At the same time, the variability of heart rate signals estimated with SDNN seems to be significantly reduced during the development of septic shock.

References

    1. Abuissa H., O'Keefe J. H., Harris W., Jr., Lavie C. J. (2005). Autonomic function, Omega-3, and cardiovascular risk. Chest 127, 1088–1091
    1. Akselroad S., Gordon D., Madwed J. B., Shannon D. C., Barger A. C., Cohen R. J. (1981). Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213, 220–222
    1. Albert C. M., Ma J., Rifai N., Stampfer M. J., Ridker P. M. (2002). Prospective study of C-reactive protein, homocystein, and plasma lipid levels as predictors of sudden cardiac death. Circulation 105, 2595–2599 10.1161/01.CIR.0000017493.03108.1C
    1. Aronson D., Mittleman M. A., Burger A. J. (2001). Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure. J. Cardiovasc. Electrophysiol. 12, 294–300 10.1046/j.1540-8167.2001.00294.x
    1. Bernardi L., Salvucci F., Suardi R., Solda P. L., Salciati A., Perlini S., et al. (1990). Evidence for an intrinsic mechanism regulating heart rate variability in the transplanted and the intact heart during submaximal dynamic exercise? Cardiovasc. Res. 24, 969–981 10.1093/cvr/24.12.969
    1. Berthhoud H. R., Neuhuber W. L. (2000). Functional anatomy of afferent vagal system. Auton. Neurosci. 85, 1–17 10.1016/S1566-0702(00)00215-0
    1. Bibevski S., Dunlap M. E. (2011). Evidence for impaired vagus nerve activity in heart failure. Heart Fail Rev. 16, 129–135 10.1007/s10741-010-9190-6
    1. Bilchick K. C., Fetics B., Djoukeng R., Fisher S. G., Fletcher R. D., Singh S. N., et al. (2002). Prognostic value of heart rate variability in chronic congestive heart failure (Veterans Affairs' Survival Trial of Anti-arrhythmic Therapy in Congestive Heart Failure). Am. J. Cardiol. 90, 24–28
    1. Billman G. E. (2013). The LH/HF ratio does not accurately measure cardiac sympatho-vagal balance. Front. Physiol. 4:26. 10.3389/fphys.2013.00026
    1. Billman G. E. (2012). Effect of dietary omega-3 polyunsaturated fatty acids on heart rate and heart rate variability in animals susceptible or resistant to ventricular fibrillation. Front. Physiol. 3:71. 10.3389/fphys.2012.00071
    1. Billman G. E., Harris W. S. (2011). Effect of dietary omega-3 fatty acids on heart rate and the heart rate variability responses to myocardial ischemia or exercise. Am. J. Physiol. Heart Circ. Physiol. 300, H2288–H2299 10.1152/ajpheart.00140.2011
    1. Briest W., Holzl A., Raβler B., Deten A., Leicht M., Bada H. A., et al. (2001). Cardiac remodeling after long term norepinephrine treatment in rats. Cardiovasc. Res. 52, 265–273
    1. Brunner E. J., Hemingway H., Walker B. R., Page M., Clarke P., Juneja M., et al. (2002). Adreno-cortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study. Circulation 106, 2659–2665 10.1161/
    1. Buchman T. G. (2002). The community of the self. Nature 420, 246–251 10.1038/nature01260
    1. Calvillo L., Vanoli E., Andreoli E., Besana A., Omodeo E., Gneechi M., et al. (2011). Vagal stimulation, through its nicotinic action limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J. Cardiovasc. Pharmacol. 58, 500–507 10.1097/FJC.0b013e31822b7204
    1. Christensen J. H. (2011). Omega-3 polyunsaturated fatty acids and heart rate variability. Front. Physiol. 2:84. 10.3389/fphys.2011.00084
    1. Christensen J. H., Christensen M. S., Dyerberg J., Schmidt E. B. (1999). Heart rate variability and fatty acid content of blood cell membranes: a dose-response study with n-3 fatty acids. Am. J. Clin. Nutr. 70, 331–337
    1. Chrousos G. P. (1995). The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. New Engl. J. Med. 332, 1351–1362 10.1056/NEJM199505183322008
    1. Chung M. K., Gulik T. S., Rotondo R. E., Schreiner G. F., Lange L. G. (1990). Mechanisms of action of cytokine inhibition of β-adrenergic agonist stimulation of cyclic AMP in rat cardiac myocytes: impairment of signal transduction. Circ. Res. 67, 753–763 10.1161/01.RES.67.3.753
    1. Commural C., Singh K., Pimentel D. R., Colucci W. S. (1998). Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the β-adrenergic pathway. Circulation 98, 1329–1334 10.1161/01.CIR.98.13.1329
    1. DeBoer R. W., Karemaker J. M., Strackee J. (1987). Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model. Am. J. Physiol. 253, 680–689
    1. De Ferrari G. M., Crijns H. J., Borggrefe M., Milasinovic G., Smid J., Zabel M., et al. (2011). Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur. Heart J. 32, 847–855 10.1093/eurheartj/ehq391
    1. de Jonge W. J., van der Zanden E. P., Bijlsma M. F., van Westerloo D. J., Bennink R. J., Berthoud H. R., et al. (2005). Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat. Immun. 6, 844–851 10.1038/ni1229
    1. Dekker J. M., Schouten E. G., Klootwijk P., Pool, J, Swenne C. A., Kromhout D., et al. (1997). Heart rate variability from short electro-cardiographic recordings predicts mortality from all causes in middle-aged and elderly men. Am. J. Epidemiol. 145, 899–908 10.1093/oxfordjournals.aje.a009049
    1. Eckberg D. L. (1997). Sympathovagal balance. Circulation 96, 3224–3232 10.1161/01.CIR.96.9.3224
    1. Elenkov I. J., Wilder R. L., Chrousos G. P., Vizi E. S. (2000). The sympathetic nerve-an integrative interface between two super-systems: the brain and the immune system. Pharmacol. Rev. 52, 595–638
    1. Fairchild K. D., Saucerman J. J., Raynor L. L., Sivak J. A., Xiao Y., Lake D. E., et al. (2009). Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, 1019–1027 10.1152/ajpregu.00132.2009
    1. Fleckenstein A. (1971). Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions, in Calcium and the Heart, ed Opie H. P. (London, Academic Press: ), 135–188
    1. Frasure S. N., Lesperance F. (2006). Depression and coronary artery disease. Herz 31, 64–68
    1. Friedland J. S., Porter J. C., Daryanani S., Bland J. M., Screaton N. J., Vesely M. J., et al. (1996). Plasma proinflammatory cytokine concentrations, APACHE III scores and survival in patients in an intensive care unit. Crit. Care Med. 24, 1775–1781 10.1097/00003246-199611000-00003
    1. Gao L., Wang W., Li Y-L., Schultz H. D., Liu D., Cornisch K. G., et al. (2005). Simvastatin therapy normalizes sympathetic neural control in experimental heart failure. Roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation 112, 1763–1770 10.1161/CIRCULATIONAHA.105.552174
    1. Garder M. L., von Karel R. (2006). Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms. Eur. J. Cardiovasc. Prev. Rehabil. 13, 165–172 10.1097/01.hjr.0000214606.60995.46
    1. Godin P. J., Buchman T. G. (1996). Uncoupling of biological oscillators: a complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Crit. Care Med. 24, 1107–1116 10.1097/00003246-199607000-00008
    1. Goldberg J., Curran B., Vitek M. E., Henderson W. G., Boyko E. J. (2002). The vietnam era twin registry. Twin Res. 5, 476–481
    1. Goldberger A. L. (1996). Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside. Lancet 347, 1312–1314 10.1016/S0140-6736(96)90948-4
    1. Goldberger A. L., Amaral L. A. N., Hausdorff J. M., Ivanov P. C., Peng C. K., Stanley H. E. (2002). Fractal dynamics in physiology: alterations with disease and aging. Proc. Natl. Acad. Sci. U.S.A. 99, 2466–2472 10.1073/pnas.012579499
    1. Goldberger J. J., Challapalli S., Tung R., Parker M. A., Kadish A. H. (2001). Relationship of heart rate variability to parasympathetic effect. Circulation 103, 1977–1983 10.1161/01.CIR.103.15.1977
    1. Goldsmith R. L., Bigger J. T., Bloomfield D. M., Krum H., Steinman R. C., Sackner-Bernstein J., et al. (1997). Long-term carvedilol therapy increases parasympathetic nervous system activity in chronic heart failure. Am. J. Cardiol. 80, 1101–1104 10.1016/S0002-9149(97)00616-4
    1. Goldstein B., Buchman T. G. (1998). Heart rate variability in intensive care. Intensive Care Med. 13 252–265
    1. Goldstein B., Fiser D. H., Kelly M. M., Mickelsen D., Ruttiman U., Pollack M. M. (1998). Decomplexification in critical illness and injury: relationship between heart rate variability, severity of illness, and outcome. Crit. Care Med. 26, 352–557 10.1097/00003246-199802000-00040
    1. Griffin M. P., Lake D. E., Bissonette E. A., Harrell F. E., Micheal, O'Shea T., et al. (2005). Heart rate characteristics: novel physiomarkers to predict neonatal infection and death. Pediatrics 116, 1070–1074
    1. Haensel A., Mills P. J., Nelesen R. A., Ziegler M. G., Dimsdale J. E. (2008). The relationship between heart rate variability and inflammatory markers in cardio-vascular diseases. Psychoneuroendocrinology 33, 1305–1312 10.1016/j.psyneuen.2008.08.007
    1. Hamaad A., Sosin M., Blann A. D., Patel J., Lip G. Y. H., MacFadyen R. G. (2005). Markers of inflammation in acute coronary syndromes: association with increased heart rate and reductions in heart rate variability. Clin. Cardiol. 28, 570–576 10.1002/clc.4960281207
    1. Hauptman P. J., Schwartz P. J., Gold M. R., Borggrefe M., Van Veldhuisen D. J., Starling R. C., et al. (2012). Rational and study design of the INcrease Of Vagal TonE in Heart Failure Study: INOVATE-HF. Am. Heart J. 163, 954–962 10.1016/j.ahj.2012.03.021
    1. Hrushesky W. J., Fader D., Schmitt O., Gilbertsen V. (1984). The respiratory sinus arrhythmia: a measure of cardiac age. Science 224, 1001–1004 10.1126/science.6372092
    1. Huston J. M., Ochani M., Rosas-Ballina M., Liao H., Ochani K., Pavlov V. A., et al. (2006). Splenectomy inactivates the cholinergic anti-inflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J. Exp. Med. 203, 1623–1628 10.1084/jem.20052362
    1. Janszky I., Ericson M., Lekander M., Blom M., Buhlin K., Georgiades A., et al. (2004). Inflammatory markers and heart rate variability in women with coronary heart disease. J. Intern. Med. 256, 421–428 10.1111/j.1365-2796.2004.01403.x
    1. Kleiger R. E., Miller J. P., Bigger J. T. (1987). Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am. J. Cardiol. 59, 256–262 10.1016/0002-9149(87)90795-8
    1. Koj A. (1997). Initiation of acute phase response and synthesis of cytokines. Biochim. Biophys. Acta 1317, 84–94
    1. Kop W. J., Stein P. K., Tracy R. P., Barzilay J. I., Schulz R., Gottdiener J. S. (2010). Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression. Psychosom. Med. 72, 626–635 10.1097/PSY.0b013e3181eadd2b
    1. Kox M., Ramakers B. P., Pompe J. C., van der Hoeven J. C., Hoedemaekers C. W., Pickkers P. (2011). Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers. Shock 36, 115–120 10.1097/SHK.0b013e31821c2330
    1. La Rovera M. T., Bigger J. T., Marcus F. I., Mortara A., Maestri R., Schwartz P. J. (1998). Baroreflex sensitivity and heart rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351, 478–484 10.1016/S0140-6736(97)11144-8
    1. Lampert J. R., Ickovics R., Viscoli C. J., Horwitz R. I., Lee F. A. (2003). Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the beta-blocker heart attack trial. Am. J. Cardiol. 91, 137–142 10.1016/S0002-9149(02)03098-9
    1. Lampert R., Bremmer J. D., Su S., Miller A., Lee F., Cheema F., et al. (2008). Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. Am. Heart J. 156, 759e1–759e7.
    1. Lanfranchi P. A., Somers V. K. (2002). Arterial baroreflex function and cardio-vascular variability: interactions and implications. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, 815–826
    1. Lanza G. A., Sgueglia G. A., Cianflone D., Rebuzzi A. G., Angeloni G., Sestito A., et al. (2006). Relation of heart rate variability to serum levels of C-reactive protein in patients with unstable angina pectoris. Am. J. Cardiol. 97, 1702–1706 10.1016/j.amjcard.2006.01.029
    1. Lefer D. J. (2002). Statins as potent anti-inflammatory drugs. Circulation 106, 2041–2042 10.1161/01.CIR.0000033635.42612.88
    1. Li M., Zheng C., Sato T., Kawada T., Sugimachi M., Sunagawa K. (2004). Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109, 120–124 10.1161/01.CIR.0000105721.71640.DA
    1. Lombardi F., Sandrone G., Pernptuner S., Sala R., Garimoldi M., Cerutti S., et al. (1987). Heart rate variability as an index of sympathovagal interaction after myocardial infarction. Am. J. Cardiol. 60, 1239–1245 10.1016/0002-9149(87)90601-1
    1. Madsen T., Christensen J. H., Toft E., Schmidt E. B. (2007). C-reactive protein is associated with heart rate variability. Ann. Noninvasive Electrocardiol. 12, 216–222 10.1111/j.1542-474X.2007.00164.x
    1. Malave H. A., Taylor A. A., Nattama J., Deswal A., Mann D. L. (2003). Circulating levels of tumor necrosis factor correlate with indexes of depressed heart rate variability. Chest 123, 716–724 10.1378/chest.123.3.716
    1. Malik M., Camm A. J. (1993). Components of heart rate variability: what they really mean and what we really measure. Am. J. Cardiol. 72, 821–822 10.1016/0002-9149(93)91070-X
    1. Malpas S. C. (2002). Neural influences on cardiovascular variability: possibilities and pitfalls. Am. J. Physiol. Heart Circ. Physiol. 282, H6–H20
    1. Mann D. L., Kent R. L., Parsons B., Cooper G. (1992). Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 85, 790–804 10.1161/01.CIR.85.2.790
    1. Montano N., Gnecchi-Ruscone T., Porta A., Lombardi F., Malliani A., Barman S. M. (1996). Presence of vasomotor and respiratory rhythms in the discharge of single medullary neurons involved in the regulation of cardiovascular system. J. Auton. Nerv. Syst. 57, 116–122 10.1016/0165-1838(95)00113-1
    1. Mozaffarian D., Stein P. K., Prineas R. J., Siscovick D. S. (2008). Dietary Fish ω-3 fatty acid consumption and heart rate variability in US adults. Circulation 117, 1130–1137 10.1161/CIRCULATIONAHA.107.732826
    1. Muller-Werdan U., Buerke M., Ebelt H., Heinroth K. M., Herklotz A., Loppnow H., et al. (2006). Septic cardiomyopathy-a not yet discovered cardiomyopathy? Exp. Clin. Cardiol. 11, 226–236
    1. Nolan R. P., Reid G. J., Seidelin P. H., Lau H. K. (2007). C-reactive protein modulates vagal heart rate control in patients with coronary artery disease. Clin. Sci. 112, 449–456 10.1042/CS20060132
    1. Opie L. H., Walpoth B., Barsacchi R. (1985). Calcium and catecholamines: Rele-vance to cardiomyopathies and significance to therapeutic strategies. J. Mol. Cell Cardiol. 17, 21–34 10.1016/0022-2828(85)90005-7
    1. Owen N., Steptoe A. (2003). Natural killer cell and proinflammatory cytokine responses to mental stress: associations with heart rate and heart rate variability. Biol. Psychol. 63, 101–115 10.1016/S0301-0511(03)00023-1
    1. Papaioannou V., Dragoumanis C., Theodorou V., Gargaretas C., Pneumatikos I. (2009). Relation of heart rate variability to serum levels of C-reactive protein, interleukin 6 and 10 in patients with sepsis and septic shock. J. Crit. Care 24, 625e1–625e7.
    1. Phillips A. N., Neaton J. D., Cook D. G., Grimm R. H., Shaper A. G. (1992). Leukocyte count and risk of major coronary heart disease events. Am. J. Epidemiol. 136, 59–70
    1. Pizzi C., Manzoli L., Mancini S., Maria-Costa G. (2008). Analysis of potential predictors of depression among coronary heart disease risk factors including heart rate variability, markers of inflammation and endothelial function. Eur. Heart J. 29, 1110–1117 10.1093/eurheartj/ehn137
    1. Pliquett R. U., Cornish K. G., Zucker I. H. (2002). Statin therapy restores sympathovagal balance in experimental heart failure. J. Appl. Physiol. 95, 700–704
    1. Pontes-Arruda A., Aragao A. M., Albuquerque J. D. (2006). Effects of enteral feeding with eicosa-pentaenoic acid, gamma-linolenic acid, and anti-oxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit. Care Med. 34, 2325–2333 10.1097/01.CCM.0000234033.65657.B6
    1. Priori S. G., Aliot E., Blomstrom-Lundqvist C., Bossaert L., Breithardt G., Brugada P., et al. (2001). Task force on sudden cardiac death of the european society of cardiology. Eur. Heart J. 16, 1374–1450 10.1053/euhj.2001.2824
    1. Psychari S. N., Apostolou T. S., Iliodromitis E. K., Kourakos P., Liakos G., Kremastinos D. T. (2007). Inverse relation of C-reactive protein levels to heart rate variability in patients after acute myocardial infarction. Hellenic. J. Cardiol. 48, 64–71
    1. Reichilin S. (1993). Neuroendocrine-immune interactions. New Engl. J. Med. 329, 1246–1253 10.1056/NEJM199310213291708
    1. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. (1997). Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. New Engl. J. Med. 336, 973–979 10.1056/NEJM199704033361401
    1. Rona G., Chappel G. I., Balazs T., Gaudry R. (1959). An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch. Pathol. 67, 443–455
    1. Ross T. (1993). The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801–809 10.1038/362801a0
    1. Sajadieh A., Nielsen O. W., Rasmussen V., Hein H. O., Abedini S., Hansen J. F. (2004). Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur. Heart J. 25, 363–370 10.1016/j.ehj.2003.12.003
    1. Schwartz P. J., De Ferrari G. M., Sanzo A., Landolina M., Rordorf R., Raineri C., et al. (2008). Long term vagal stimulation in patients with advanced heart failure. First experience in man. Eur. J. Heart Fail 10, 884–891 10.1016/j.ejheart.2008.07.016
    1. Seely A. J. E., Christou N. V. (2000). Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Crit. Care Med. 28, 2193–2200 10.1097/00003246-200007000-00003
    1. Shehab A. M., MacFadyen R. J., McLaren M., Tavendale R., Belch J. J., Struthers A. D. (2004). Sudden unexpected death in heart failure may be preceded by short term, intra-individual increases in inflammation and in autonomic dys-function: a pilot study. Heart 90, 1263–1268 10.1136/hrt.2003.028399
    1. Sherry R. M., Cue J. I., Gobbard J. K., Parramore J. B., DiPiro J. T. (1996). Interleukin-10 is associated with the development of sepsis in trauma patients. J. Trauma. 40, 613–616 10.1097/00005373-199604000-00016
    1. Singer P., Shapiro H., Theilla M., Anbar R., Singer J., Cohen J. (2008). Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensive Care Med. 34, 1580–1592 10.1007/s00134-008-1142-4
    1. Singer P., Theilla M., Fisher H., Gibstein L., Grozovski E., Cohen J. (2006). Benefit of an enteral diet enriched with eico-sapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit. Care Med. 34, 1033–1038 10.1097/01.CCM.0000206111.23629.0A
    1. Sloan R. P., McCreath H., Tracey K. J., Sidney S., Liu K., Seeman T. (2007). RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol. Med. 13, 178–184
    1. Sporn M. B. L. (1997). The importance of context in cytokine action. Kidney Int. 51, 1352–1354 10.1038/ki.1997.184
    1. Task Force of the European Society of Cardiology the North American Society of Pacing and Electrophysiology. (1996). Standards of measurement, physio-logical interpretation and clinical use Circulation 93, 1043–1065 10.1161/01.CIR.93.5.1043
    1. Tateishi Y., Oda S., Nakamura M., Watanabe K., Kuwaki T., Moriguchi T., et al. (2007). Depressed heart rate variability is associated with high IL-6 blood level and decline in blood pressure in septic patients. Shock 28, 549–553 10.1097/shk.0b013e3180638d1
    1. Tracey K. J. (2002). The inflammatory reflex. Nature 420, 853–859 10.1038/nature01321
    1. Tracey K. J. (2007). Physiology and immunology of the cholinergic anti-inflammatory pathway. J. Clin. Invest. 117, 289–296 10.1172/JCI30555
    1. Tsuji H., Venditti F. J., Manders E. S., Evans J. C., Larson M. G., Feldman C. L., et al. (1994). Reduced heart rate variability and mortality risk in an elderly cohort: the Framingham Heart Study. Circulation 90, 878–883 10.1161/01.CIR.90.2.878
    1. van der Poll T., Coyle S. M., Barbosa K., Braxton C. C., Lowry S. F. (1996). Epinephrine inhibits tumor necrosis factor-α and potentiates interleukin-10 production during human endotoxemia. J. Clin. Invest. 97, 713–719 10.1172/JCI118469
    1. Verkerk A. O., den Ruijiter H. M., Bourier J., Boukens B. J., Brouwer I. A., Wilders R., et al. (2009). Dietary fish oil reduces pacemaker current and heart rate in rabbit. Heart Rhythm 6, 1485–1492 10.1016/j.hrthm.2009.07.024
    1. von Känel R., Carney R. M., Zhao S., Whooley M. A. (2011). Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart diseases: finding from the Heart and Soul Study. Clin. Res. Cardiol. 100, 241–247 10.1007/s00392-010-0236-5
    1. Vrtovec B., Okrajsek R., Golisnik A., Ferjan M., Starc V., Radovancevic B. (2005). Atorvastatin therapy increases heart rate variability, decreases QT variability and shortens QTc interval duration in patients with advanced chronic heart failure. J. Card. Fail. 11, 684–690
    1. Wang H., Liao H., Ochani M., Justiniani M., Lin X., Yang L., et al. (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat. Med. 10, 1216–1221 10.1038/nm1124
    1. Wang H., Yu M., Ochani M., Amella CA., Tanovic M., Susarla S., et al. (2003). Nicotinic acetylcholine receptor α 7 subunit is an essential regulator of inflammation. Nature 421, 384–388 10.1038/nature01339
    1. Webster J. I., Tonelli L., Sternberg E. M. (2002). Neuroendocrine regulation of immunity. Annu. Rev. Immunol. 20, 125–163 10.1146/annurev.immunol.20.082401.104914
    1. Welzig C. M., Shin D.-G., Park H.-J., Kim Y. J., Saul J. P., Galper J. B. (2003). Lipid lowering by pravastatin increases parasympathetic modulation of heart rate: G(alpha) i2, a possible molecular marker for parasympathetic responsiveness. Circulation 108, 2743–2746 10.1161/01.CIR.0000103680.61390.16
    1. Wolf M. M., Varigos G. A., Hunt D., Sloman J. G. (1978). Sinus arrhythmia in acute myocardial infarction. Med. J. Aust. 2, 52–53
    1. Zaza A., Lombardi F. (2001). Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node. Cardiovsc. Res. 50, 434–442 10.1016/S0008-6363(01)00240-1
    1. Zhang Y., Popovic Z. B., Bibevski S., Fakhry I., Sica D. A., Van Wagoner D. R., et al. (2009). Chronic vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circ. Heart Fail 2, 692–699
    1. Zhou M., Yang S., Koo D. J., Ornan D. A., Chaudry I. H., Wang P. (2001). The role of Kupffer cell α2adrenoceptors in norepinephrine-induced TNF-α production. Biochim. Biophys. Acta 1537, 49–57 10.1016/S0925-4439(01)00055-2

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다