title: Relationship of basal heart rate variability to in vivo cytokine responses after endotoxin exposure.
abstract: Autonomic inputs from the sympathetic and parasympathetic nervous systems, as measured by heart rate variability (HRV), have been reported to correlate to the severity injury and responses to infectious challenge among critically ill patients. In addition, parasympathetic/vagal activity has been shown experimentally to exert anti-inflammatory effects via attenuation of splanchnic tissue TNF-alpha production. We sought to define the influence of gender on HRV responses to in vivo endotoxin challenge in healthy humans and to determine if baseline HRV parameters correlated with endotoxin-mediated circulating cytokine responses. Young (<30 years of age), healthy subjects (n = 30) received endotoxin (2 ng/kg), and HRV and blood samples were obtained serially thereafter. Plasma cytokines were measured by enzyme-linked immunosorbent assay, and HRV parameters were determined by analysis of serial 5-min epochs of heart rate monitoring. In addition, calculation of multiscale entropy deriving from cardiac monitoring data was performed. The influence of factors such as gender, body mass index, and resting heart rate on HRV after endotoxin exposure was assessed. We found that gender, body mass index, or resting heart rate did not significantly alter the HRV response after endotoxin exposure. Using entropy analysis, we observed that females had significantly higher entropy values at 24 h after endotoxin exposure. Using a serially sampling protocol for cytokine determination, we found a significant correlation of several baseline HRV parameters (percentage of interval differences of successive interbeat intervals more than 50 ms, r = 0.42, P < 0.05; high-frequency variability, r = 0.4, P < 0.05; and low-frequency/high-frequency ratio, r = -0.43, P < 0.05) on TNF-alpha release after endotoxin exposure.
authors.affiliation: Department of Surgery, Division of Surgical Sciences, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
authors.forename: Badar U
authors.initials: BU
authors.lastname: Jan
authors.forename: Susette M
authors.initials: SM
authors.lastname: Coyle
authors.forename: Marie A
authors.initials: MA
authors.lastname: Macor
authors.forename: Michael
authors.initials: M
authors.lastname: Reddell
authors.forename: Steve E
authors.initials: SE
authors.lastname: Calvano
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000328:Adult; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000494:pharmacology*; D019277:Entropy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D012737:Sex Factors
chemical_list: D016207:Cytokines; D004731:Endotoxins
references.citation: J Cardiovasc Electrophysiol. 2003 Aug;14(8):791-9
references.pmid: 12890036
references.citation: Am J Cardiol. 1999 Apr 15;83(8):1242-7
references.pmid: 10215292
references.citation: Clin Exp Immunol. 1999 Nov;118(2):235-41
references.pmid: 10540184
references.citation: Curr Opin Crit Care. 2005 Oct;11(5):449-53
references.pmid: 16175031
references.citation: Surg Clin North Am. 2009 Apr;89(2):311-26, vii
references.pmid: 19281886
references.citation: Ann Noninvasive Electrocardiol. 2008 Jul;13(3):270-7
references.pmid: 18713328
references.citation: Biophys J. 1965 Mar;5:145-62
references.pmid: 14268950
references.citation: Psychosom Med. 2007 Nov;69(8):709-16
references.pmid: 17942840
references.citation: J Pathol. 2007 Jan;211(2):144-56
references.pmid: 17200946
references.citation: Crit Care Med. 1996 Jul;24(7):1117-24
references.pmid: 8674322
references.citation: Shock. 2006 Dec;26(6):538-43
references.pmid: 17117126
references.citation: Nature. 2003 Jan 23;421(6921):384-8
references.pmid: 12508119
references.citation: J Trauma. 2006 Feb;60(2):363-70; discussion 370
references.pmid: 16508497
references.citation: J Exp Med. 2006 Jul 10;203(7):1623-8
references.pmid: 16785311
references.citation: J Trauma. 2006 Jun;60(6):1165-73; discussion 1173-4
references.pmid: 16766957
references.citation: Circulation. 1996 Mar 1;93(5):1043-65
references.pmid: 8598068
references.citation: Ann Surg. 2006 Jun;243(6):804-12; discussion 812-4
references.pmid: 16772784
references.citation: J Endotoxin Res. 2007;13(6):358-68
references.pmid: 18182463
references.citation: J Trauma. 1997 Dec;43(6):927-33
references.pmid: 9420107
references.citation: Clin Exp Immunol. 2007 Jan;147(1):28-34
references.pmid: 17177960
references.citation: Crit Care Med. 2008 Feb;36(2):580-7
references.pmid: 18091542
references.citation: Arthritis Rheum. 2002 Jan;46(1):250-8
references.pmid: 11817599
references.citation: Psychosom Med. 2001 Sep-Oct;63(5):788-96
references.pmid: 11573027
references.citation: Psychophysiology. 1997 Nov;34(6):623-48
references.pmid: 9401419
references.citation: Crit Care Med. 1996 Jul;24(7):1107-16
references.pmid: 8674321
references.citation: J Immunol. 1993 Mar 1;150(5):1999-2006
references.pmid: 8436830
references.citation: Shock. 2007 Dec;28(6):700-3
references.pmid: 17621262
references.citation: Clin Auton Res. 2005 Apr;15(2):107-15
references.pmid: 15834767
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R145-51
references.pmid: 17428894
references.citation: Crit Care Med. 2008 Mar;36(3):1025-7
references.pmid: 18431317
references.citation: Crit Care Med. 2001 Jul;29(7):1380-5
references.pmid: 11445691
references.citation: Ann Surg. 2009 May;249(5):750-6
references.pmid: 19387330
references.citation: Acad Emerg Med. 2007 May;14(5):392-7
references.pmid: 17389245
references.citation: J Natl Med Assoc. 1999 Jul;91(7):384-8
references.pmid: 10643210
references.citation: J Intern Med. 2005 Feb;257(2):156-66
references.pmid: 15656874
references.citation: Shock. 2008 Jul;30(1):17-22
references.pmid: 18323736
references.citation: Ann N Y Acad Sci. 2006 Nov;1088:361-72
references.pmid: 17192580
references.citation: Biol Psychol. 2007 Feb;74(2):165-73
references.pmid: 17045727
references.citation: J Infect Dis. 2005 Jun 15;191(12):2138-48
references.pmid: 15898001
references.citation: Psychosom Med. 1998 Nov-Dec;60(6):773-81
references.pmid: 9847039
references.citation: Shock. 2005 Dec;24 Suppl 1:94-100
references.pmid: 16374380
references.citation: Curr Opin Crit Care. 2002 Aug;8(4):311-5
references.pmid: 12386491
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R927-31
references.pmid: 14557228
references.citation: J Neurol Neurosurg Psychiatry. 2002 Jun;72(6):726-31
references.pmid: 12023413
references.citation: J Infect Dis. 1996 Nov;174(5):1040-5
references.pmid: 8896506
references.citation: Shock. 2007 Nov;28(5):549-53
references.pmid: 18075483
references.citation: Circulation. 2004 Nov 2;110(18):2786-91
references.pmid: 15505096
references.citation: J Clin Invest. 1996 Feb 1;97(3):713-9
references.pmid: 8609227
references.citation: Bull World Health Organ. 1995;73(5):673-80
references.pmid: 8846494
references.citation: J Appl Physiol (1985). 2007 Sep;103(3):1007-11
references.pmid: 17626836
references.citation: J Crit Care. 2008 Sep;23(3):399-405
references.pmid: 18725047
references.citation: Phys Rev Lett. 2002 Aug 5;89(6):068102
references.pmid: 12190613
references.citation: Am J Emerg Med. 2008 May;26(4):395-401
references.pmid: 18410805
references.citation: Nat Rev Immunol. 2009 Jun;9(6):418-28
references.pmid: 19461672
references.citation: Clin Invest Med. 2006 Feb;29(1):20-8
references.pmid: 16553360
references.citation: Nature. 2000 May 25;405(6785):458-62
references.pmid: 10839541
references.citation: J Mol Med (Berl). 2007 Nov;85(11):1239-51
references.pmid: 17657467