Skip to main content

Pathophysiological and Systems Biology Considerations

  • Chapter
  • First Online:
  • 3834 Accesses

Abstract

Outline: In this chapter some general arguments about the significance of changed time series patterns as a surrogate of a system are presented. I introduce the idea of decreased heart rate variability as a sign for illness and emphasize specially entropy and other nonlinear parameters. In the next section several subsystems of the body that may influence heart rate variability are discussed. I include commonly known (and already mentioned) elements, like the autonomic nervous system, the lung and the circulatory system, as well as other peripheral parts, such as the endocrinological system in general or the immune system. This discussion will be essential for the next chapter, in which I present and discuss different models for heart rate variability.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Aguilera G. Corticotropin releasing hormone, receptor regulation and the stress response. Trends Endodrinol Metab. 1998;9:329–36.

    CAS  Google Scholar 

  • Ahren B, Taborsky GJ, Porte D. Neuropeptidergic versus cholinergic and adrenergic regulation of islet hormone secretion. Diabetologia. 1986;29:827–36.

    PubMed  CAS  Google Scholar 

  • Althaus M, Mulder LJM, Mulder G, van Roon AM, Minderaa RB. Influence of respiratory activity on the cardiac response pattern to mental effort. Psychophysiology. 1998;35:420–30.

    PubMed  CAS  Google Scholar 

  • Aon MA, Cortassa S, O’Rourke BO. The fundamental organization of cardiac mitochondria as a network of coupled oscillators. Biophys J. 2006;91:4317–27.

    PubMed  CAS  Google Scholar 

  • Aoyagi N, Ohashi K, Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol. 2003;285:R171–6.

    CAS  Google Scholar 

  • Araujo F, Antelmi I, Pereira AC, et al. Lower heart rate variability is associated with higher serum high-sensitivity C-reactive protein concentration in healthy individuals aged 46 or more. Int J Cardiol. 2006;107:333–7.

    PubMed  Google Scholar 

  • Aronson D, Mittleman MA, Burger AJ. Role of endothelin in modulation of heart rate variability in patients with decompensated heart failure. Pacing Clin Electrophysiol. 2001a;24:1607–15.

    PubMed  CAS  Google Scholar 

  • Aronson D, Mittleman MA, Burger AJ. Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure. J Cardiovasc Electrophysiol. 2001b;12:294–300.

    PubMed  CAS  Google Scholar 

  • Bathnagar S, Dallman M. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neuroscience. 1998;84:1025–39.

    Google Scholar 

  • Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15:74–80.

    PubMed  CAS  Google Scholar 

  • Barnett PA, Spence JD, Manuck SB, Jennings JR: Psychological stress and the progression of carotid artery disease. J Hypertens 1997;15:49–55.

    PubMed  CAS  Google Scholar 

  • Bergfeldt L, Haga Y. Power spectral and Poincaré plot characteristics in sinus node dysfunction. J Appl Physiol. 2003;94:2217–24.

    PubMed  Google Scholar 

  • Berntson GG, Bigger Jr JT, Eckberg DL, Grossman P, Kaufmann PG, Malik M, Nagaraja HN, Porges SW, Saul JP, Stone PH, van der Molen MW. Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology. 1997;34:623–48.

    PubMed  CAS  Google Scholar 

  • Berthoud HR, Jeanrenaud B. Acute hyperinsulinemia and its reversal by vagotomy after lesions of the ventromedial hypothalamus in anesthetized rats. J Clin Invest. 1979;105:146–51.

    CAS  Google Scholar 

  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458–61.

    PubMed  CAS  Google Scholar 

  • Boucsein W, Backs RW, editors. Engineering psychophysiology: issues and applications. London: Lawrence Erlbaum; 2000.

    Google Scholar 

  • Buccelletti F, Bocci MG, Gilardi E, Fiore V, Calcinaro S, Fragnoli C, Maviglia R, Franceschi F. Linear and nonlinear heart rate variability indexes in clinical practice. Comput Math Methods Med. 2012; Article ID 219080. doi:10.1155/2012/219080.

  • Cacioppo JT, Malarkey WB, Kiecolt-Glaser JK, Uchino BN, Sgoutas-Emch SA, Sheridan JF, Berntson GG, Glaser R. Heterogeneity in neuroendocrine and immune responses to brief psychological stressors as a function of autonomic cardiac activation. Psychosom Med. 1995;57:154–64.

    PubMed  CAS  Google Scholar 

  • Carney RM, Freedland KE, Veith RC: Depression, the autonomic nervous system and coronary heart disease. Psychosom Med 2005;67 (Suppl 1): S29–S33.

    PubMed  Google Scholar 

  • Carney RM, Freedland KE, Stein PK, et al. Heart rate variability and markers of inflammation and coagulation in depressed patients with coronary heart disease. J Psychosom Res. 2007;62:463–7.

    PubMed  Google Scholar 

  • Cooley RL, Montano N, Cogliati C, van de Borne P, Richenbacher W, Oren R, Somers VK. Evidence for a central origin of the low frequency oscillation in RR-interval variability. Circulation. 1998;98:556–61.

    PubMed  CAS  Google Scholar 

  • Dallman MF, La Fluer S, Pecoraro NC, Gomez F, Houshyar H, Akana SF. Minreview: glucocorticoids- food intake, abdominal obesity, and wealthy nations in 2004. Endocrinology. 2004;145:2633–8.

    PubMed  CAS  Google Scholar 

  • Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa M, Nakazato M. Orexins, orixigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci. 1999;96:748–53.

    PubMed  CAS  Google Scholar 

  • Degangi GA, DiPietro JA, Greenspan SI, Porges SW. Psychophysiological characteristics of the regularly disordered infant. Infant Behav Dev. 1991;14:37–50.

    Google Scholar 

  • Denver JW, Reed SF, Porges SW. Methodological issues in the quantification of respiratory sinus arrhythmia. Biol Psychol. 2007;74:286–94.

    PubMed  Google Scholar 

  • Duschek S, Muckenthaler M, Werner N, del Paso GA. Relationships between features of autonomic cardiovascular control and cognitive performance. Biol Psychol. 2009;81:110–7.

    PubMed  Google Scholar 

  • Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52:595–638.

    PubMed  CAS  Google Scholar 

  • Ferrannini E, Iozzo P. Is insulin resistance atherogenic? A review of the evidence. Atheroscler Suppl. 2006;7:5–10.

    PubMed  CAS  Google Scholar 

  • Gaykema RPA, Dijkstra I, Tilders FJH. Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of hypothalamic corticotropin-releasing hormones neurons and ACTH secretion. Endocrinology. 1995;136:4717–20.

    PubMed  CAS  Google Scholar 

  • Glynn LM, Christenfeld N, Gerin W. The role of rumination in recovery from reactivity: cardiovascular consequences of emotional states. Psychosom Med. 2002;64:714–26.

    PubMed  Google Scholar 

  • Goehler LE, Gaykema RP, Nguyen KT, Lee JE, Filder FJ, Maier SF, Watkins LR. Interleukin-1 in immune cells of the abdominal vagus nerve: a link between the immune and the nervous system? J Neurosci. 1999;19:2799–806.

    PubMed  CAS  Google Scholar 

  • Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci. 2000;85:49–59.

    PubMed  CAS  Google Scholar 

  • Goldberger AL. Fractal variability versus pathological periodicity: complexity loss and stereotypy in disease. Perspect Biol Med. 1997;40:543–61.

    PubMed  CAS  Google Scholar 

  • González-Clemente JM, Vilardell C, Broch M, Megia A, Caixàs A, Giménez-Palop O, Richart C, Simón I, Martínez-Riquelme A, Arroyo J, Mauricio D, Vendrell J. Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes. Eur J Endocrinol. 2007;157:31–8.

    PubMed  Google Scholar 

  • Haensel A, Mills PJ, Nelesen RA, et al. The relationship between heart rate variability and inflammatory markers in cardiovascular diseases. Psychoneuroendocrinology. 2008;33:1305–12.

    PubMed  CAS  Google Scholar 

  • Hansen MK, Nguyen KT, Fleshner M, Goehler LE, Gaykema RP, Maier SF, Watkins LR. Effects of vagotomy on serum endotoxine, cytokines and corticosterone after intraperitoneal lipopolysaccharide. Am J Physiol. 2000;278:R331–6.

    CAS  Google Scholar 

  • Hartman ML, Pincus SM, Johnson ML, Matthews DH, Faunt LM, Vance ML. Enhanced basal and disorderly growth hormone (GH) secretion distinguish acromegalic from normal pulsatile GH release. J Clin Invest. 1994;94:1277–88.

    PubMed  CAS  Google Scholar 

  • Hayano J, Yasuma F, Okada A, Mukai S, Fujinami T. Respiratory sinus arrhythmia. A phenomenon improving pulmonary gas exchange and circulatory efficiency. Circulation. 1996;94:842–7.

    PubMed  CAS  Google Scholar 

  • Herrmann GE, Emch GS, Tovar CA, Rogers RC. C-fos generation in the dorsal vagal complex after systemic endotoxin is not dependent on the vagus nerve. Am J Physiol. 2001;280:R289–99.

    Google Scholar 

  • Ishizuka Y, Ishida Y, Kunitake T, Kato K, Hanamori T, Mitsuyama Y, Kannan H. Effects of area postrema lesion and abdominal vagotomy on interleukin 1beta-induced norepinephrine release in the hypothalamic paraventricular nucleus region in the rat. Neurosci Lett. 1997;223:57–60.

    PubMed  CAS  Google Scholar 

  • Ivanov PC, Nunes Amaral LA, Goldberger AL, Havlin S, Rosenblum MG, Struzik ZR, Stanley HE. Multifractality in human heartbeat dynamics. Nature. 1999;399:461–5.

    PubMed  CAS  Google Scholar 

  • Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840–6.

    PubMed  CAS  Google Scholar 

  • Karasek R, Baker D, Marxer F, Ahlbom A, Theorell T. Job decision latitude, job demands, and cardiovascular disease: a prospective study of Swedish men. Am J Public Health. 1981;71:694–705.

    PubMed  CAS  Google Scholar 

  • Kawashima K, Fuji T. Extraneural cholinergic system in lymphocytes. Pharmacol Ther. 2000;86:29–48.

    PubMed  CAS  Google Scholar 

  • Kemp AH, Quintana DS, Kuhnert RL, Griffiths K, Hickie IB, Guastella AJ. Oxytocin increases heart rate variability in humans at rest: implications for social approach-related motivation and capacity for social engagement. PLoS One. 2012;7(8):e44014.

    PubMed  CAS  Google Scholar 

  • Kiyono K, Struzik ZR, Aoyagi N, Sakata R, Hayano J, Yamamoto Y. Critical scale invariance in a healthy human heart rate. Phys Rev Lett. 2004;93:178103.

    PubMed  Google Scholar 

  • Kiyono K, Struzik ZR, Aoyagi N, Togo F, Yamamoto Y. Phase transition in a healthy human heart rate. Phys Rev Lett. 2005;95:058101.

    PubMed  Google Scholar 

  • Koivikko ML, Salmela PI, Airaksinen KE, Tapanainen JS, Ruokonen A, Mäkikallio TH, Huikuri HV. Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes. Diabetes. 2005;54:744–50.

    PubMed  CAS  Google Scholar 

  • Kon H, Nagano M, Tanaka F, et al. Association of decreased variation of R-R interval and elevated serum c-reactive protein level in a general population in Japan. Int Heart J. 2006;47:867–76.

    PubMed  CAS  Google Scholar 

  • Kop WJ, Stein PK, Tracy RP, Barzilay JI, Schulz R, Gottdiener JS. Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression. Psychosom Med. 2010;72:626–35.

    PubMed  Google Scholar 

  • Leung RS, Bowman ME, Diep TM, Lorenzi-Filho G, Floras JS, Bradley TD. Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure. J Appl Physiol. 2005;99:1689–96.

    PubMed  Google Scholar 

  • Lieb DC, Parson HK, Mamikunian G, Vinik AI. Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation. Exp Diabetes Res. 2012;2012:878760.

    PubMed  Google Scholar 

  • Lipsitz LA. Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol. 2002;57A:B115–25.

    Google Scholar 

  • Lipsitz LA, Goldberger AL. Loss of ‘complexity’ and aging potential applications of fractals and chaos theory to senescence. JAMA. 1992;267:1806–9.

    PubMed  CAS  Google Scholar 

  • Malave HA, Taylor AA, Nattama J, Deswal A, Mann DL. Circulating levels of tumor necrosis factor correlate with indexes of depressed heart rate variability. Chest. 2003;123:716–24.

    PubMed  CAS  Google Scholar 

  • Malpas SC. Neural influences on cardiovascular variability: possibilities and pitfalls. Am J Physiol Heart Circ Physiol. 2002;282:H6–20.

    PubMed  CAS  Google Scholar 

  • Mani AR, Montagnese S, Jackson CD, Jenkins CW, Head IM, Stephens RC, Moore KP, Morgan MY. Decreased heart rate variability in patients with cirrhosis relates to the presence and severity of hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2009;296:G330–8.

    PubMed  CAS  Google Scholar 

  • Mathe G. The need of a physiologic and pathophysiologic definition of stress. Biomed Pharmacother. 2000;54:119–21.

    PubMed  CAS  Google Scholar 

  • Mathews KA, Owens JF, Kuller KH, Sutton-Tyrell K, Lassila HC, Wolfson SK. Stress induced pulse pressure change predict women’s carotid atherosclerosis. Stroke. 1998;29:1525–30.

    Google Scholar 

  • Miller DB, O’Callagan JP. Neuroendocrine aspects of the response to stress. Metabolism. 2002;51(Suppl1):5–10.

    PubMed  CAS  Google Scholar 

  • Mioni C, Bazzani C, Giuliani D, et al. Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats. Crit Care Med. 2005;33:2621–8.

    PubMed  CAS  Google Scholar 

  • Mulders HPG, Meijman TF, O’Hanlon JF, Mulder G. Differential psychophysiological reactivity of city bus drivers. Ergonomics. 1982;25:1003–11.

    PubMed  CAS  Google Scholar 

  • Nigro J, Osman N, Dart AM, Little PJ. Insulin resistance and atherosclerosis. Endocr Rev. 2006;27:242–59.

    PubMed  CAS  Google Scholar 

  • Pasquali R, Vicennati V. Activity of the hypothalamic-pituitary-adrenal axis in different obesity phenotypes. Int J Obes. 2000;24 Suppl 2:S47–9.

    CAS  Google Scholar 

  • Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003;9:125–34.

    PubMed  CAS  Google Scholar 

  • Pilowsky P. Good vibrations? Respiratory rhythms in the central control of blood pressure. Clin Exp Pharmacol Physiol. 1995;22:594–604.

    PubMed  CAS  Google Scholar 

  • Pincus SM. Greater signal regularity may indicate increased system isolation. Math Biosci. 1994;122:161–81.

    PubMed  CAS  Google Scholar 

  • Pincus S, Singer BH. Randomness and degrees of irregularity. Proc Natl Acad Sci U S A. 1996;93:2083–8.

    PubMed  CAS  Google Scholar 

  • Pincus SM, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD. Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. Proc Natl Acad Sci U S A. 1996;93:14100–5.

    PubMed  CAS  Google Scholar 

  • Pontiroli AE, et al. Body weight and glucose metabolism have a different effect on circulating levels of ICAM-1; E-selcetin and endothelin- 1 in humans. Eur J Endocrinol. 2004;150:195–200.

    PubMed  CAS  Google Scholar 

  • Rivest S. How circulating cytokines trigger the neural circuits that control the hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology. 2001;26:761–88.

    PubMed  CAS  Google Scholar 

  • Rosol TJ, Yarrington JT, Latendresse J, et al. Adrenal gland: structure, function, and mechanisms of toxicity. Toxicol Pathol. 2001;29:41–8.

    PubMed  CAS  Google Scholar 

  • Rozanski A, Kubzansky LD. Psychologic functioning and physical health: a paradigm of flexibility. Psychosom Med. 2005;67(Suppl1):S47–53.

    PubMed  Google Scholar 

  • Rozanski A, Blumenthal JA, Davidson KW, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging fields of behavioural cardiology. J Am Coll Cardiol. 2005;45:637–51.

    PubMed  Google Scholar 

  • Saeed RW, Varma S, Peng-nemeroff T, et al. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2005;201:1113–23.

    PubMed  CAS  Google Scholar 

  • Saeki Y, Atogami F, Rakahashi K, Yoshizawa T. Reflex control of autonomic function induced by posture change during the menstrual cycle. J Auton Nerv Syst. 1997;66:69–74.

    PubMed  CAS  Google Scholar 

  • Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8:171–81.

    PubMed  CAS  Google Scholar 

  • Sato N, Miyake S. Cardiovascular reactivity to mental stress: relationship with menstrual cycle and gender. J Physiol Anthropol Appl Human Sci. 2005;23:215–23.

    Google Scholar 

  • Sato KZ, Fuji T, Watanabe Y, Yamada S, Ando T, Kazuko F, Kawashima K. Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. Neurosci Lett. 1999;266:17–20.

    PubMed  CAS  Google Scholar 

  • Schlotz W, Hellhammer J, Schulz P, Stone AA. Perceived work overload and chronic worrying predict weekend-weekday differences in the cortisol awakening response. Psychosom Med. 2004;66:207–44.

    PubMed  CAS  Google Scholar 

  • Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med. 1999;160:1101–6.

    PubMed  CAS  Google Scholar 

  • Spiegel K, Leproult R, Cauter EV. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354:1435–9.

    PubMed  CAS  Google Scholar 

  • Steptoe A, Kunz-Ebrecht S, Owen N, Feldman PJ, Willemsen G, Kirschbaum C, Marmot M. Socioeconomic status and stress-related biological responses over the working day. Psychosom Med. 2003;65:461–70.

    PubMed  Google Scholar 

  • Stolarz K, Staessen JA, Kawecka Jaszcz K, Brand E, Bianchi G, Kuznetsova T, Tikhonoff V, Thijs L, Reineke T, Babeanu S, Casiglia E, Fagard R, Filipovsky J, Peleska J, Niktin Y, Struijker-Boudier H, Grodzicki T on behalf the European project on genes in hypertension (EPOGH) Investigators. Genetic variation in CYP11B2 and AT1R influences heart rate variability conditional on sodium excretion. Hypertension. 2004;44:156–62.

    Google Scholar 

  • Straburzynska-Migaj E, Ochotny R, Wachowiak-Baszynska H, Straburzynska-Lupa A, Lesniewska K, Wiktorowicz K, Cieslinski A. Cytokines and heart rate variability in patients with chronic heart failure. Kardiol Pol. 2005;63:478–85.

    PubMed  Google Scholar 

  • Struzik ZR, Hayano J, Sakata S, Kwak S, Yamamoto Y. 1/f scaling in heart rate requires antagonistic autonomic control. Phys Rev E. 2004;70:050901(R).

    Google Scholar 

  • Suadicani P, Hein HO, Gyntelberg F. Are social inequalities associated with the risk of ischemic heart disease – a result of psychosocial working conditions? Atherosclerosis. 1993;101:165–75.

    PubMed  CAS  Google Scholar 

  • Suarez EC, Kuhn CM, Schanberg SM, Williams RB, Zimmermann EA. Neuroendocrine, cardiovascular, and emotional responses of hostile men: the role of interpersonal challenge. Psychosom Med. 1998;60:78–88.

    PubMed  CAS  Google Scholar 

  • Tayebati SK, El Assouad D, Ricci A, Amenta F. Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes. J Neuroimmunol. 2002;132:147–55.

    PubMed  CAS  Google Scholar 

  • Thayer JF. On the importance of inhibition: central and peripheral manifestations of nonlinear inhibitory processes in neural systems. Dose Response. 2006;4:2–21.

    PubMed  CAS  Google Scholar 

  • Thayer JF, Friedman BH. Stop that! Inhibition, sensitization, and their neurovisceral concomitants. Scand J Psychol. 2002;43:123–30.

    PubMed  Google Scholar 

  • Thayer JF, Sternberg E. Beyond heart rate variability: vagal regulation of allostatic systems. Ann N Y Acad Sci. 2006;1088:361–72.

    PubMed  CAS  Google Scholar 

  • Thayer JF, Ahs F, Fredrikson M, Sollers 3rd JJ, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36:747–56.

    PubMed  Google Scholar 

  • Thomas KS, Nelesen RA, Ziegler MG, Bardwell WA, Dimsdale JE. Job strain, ethnicity, and sympathetic nervous system activity. Hypertension. 2004;44:895–6.

    Google Scholar 

  • Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–9.

    PubMed  CAS  Google Scholar 

  • Vaillancourt DE, Newell KM. Changing complexity in human behaviour and physiology through aging and disease. Neurobiol Aging. 2002;23:1–11.

    PubMed  Google Scholar 

  • Van Dam AM, Bol JG, Gaykema RP, Goehler LE, Maier SF, Watkins LR, Tilders FJ. Vagotomy does not inhibit high dose LPS-induced interleukin1beta immunoreactivity in the rat brain and pituitary gland. Neurosci Lett. 2000;285:169–72.

    PubMed  Google Scholar 

  • Van den Berg G, Pincus SM, Veldhuis JD, Frölich M, Roelfsema F. Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing’s disease. Eur J Endocrinol. 1997a;136:394–400.

    PubMed  Google Scholar 

  • Van den Berg MP, Haaksma J, Brouwer J, Tieleman RG, Mulder G, Crijns HJ. Heart rate variability in patients with atrial fibrillation is related to vagal tone. Circulation. 1997b;19:1209–16.

    Google Scholar 

  • Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444:875–80.

    PubMed  Google Scholar 

  • Van Roon AM, Mulder LJM, Veldmann JBP, Mulder G. Beat-to-beat blood-pressure measurements applied on studies on mental workload. Homeostasis. 1995;36:316–24.

    Google Scholar 

  • Van Westerloo DJ, Giebelen IA, Florquin S, et al. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. Gastroenterology. 2006;130:1822–30.

    PubMed  Google Scholar 

  • Veglio F, Melchio R, Rabbia F, Molino P, Martini G, Chiandussi L. Spectral characteristics of heart rate and blood pressure variability in primary aldosteronism. Am J Hypertens. 1995;8:479–86.

    PubMed  CAS  Google Scholar 

  • Veltman JA, Gaillard AWK. Indices of mental workload in a complex task environment. Neuropsychobiology. 1993;28:72–5.

    PubMed  CAS  Google Scholar 

  • Veltman JA, Gaillard AWK. Physiological workload reactions to increasing levels of task difficulty. Ergonomics. 1998;41:656–69.

    PubMed  CAS  Google Scholar 

  • Vinik AI. The conductor of the autonomic orchestra. Front Endocrinol (Lausanne). 2012;3:71.

    Google Scholar 

  • Vrijkotte TG, van Doornen LJ, de Geus EJ. Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension. 2000;44:880–6.

    Google Scholar 

  • Wang H, Yang H, Czura CJ, Sama AE, Tracey KJ. HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med. 2001;164:1768–73.

    PubMed  CAS  Google Scholar 

  • Wang H, Kiao H, Ochani M. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004;10:1216–21.

    PubMed  CAS  Google Scholar 

  • West BJ. Physiology in fractal dimensions: error tolerance. Ann Biomed Eng. 1990;18:135–49.

    PubMed  CAS  Google Scholar 

  • Yasuma F, Hayano JI. Respiratory sinus arrhythmia: why does the heartbeat synchronize with respiratory rhythm? Chest. 2004;125:683–90.

    PubMed  Google Scholar 

  • Ziegler D, Zentai CP, Perz S, et al. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study. Diabetes Care. 2008;31:556–61.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Ernst, G. (2014). Pathophysiological and Systems Biology Considerations. In: Heart Rate Variability. Springer, London. https://doi.org/10.1007/978-1-4471-4309-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4309-3_6

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4308-6

  • Online ISBN: 978-1-4471-4309-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics