Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cardiovascular Toxicology
Published in: Cardiovascular Toxicology 1/2007

01-03-2007

Heart rate variability in rodents: uses and caveats in toxicological studies

Authors: William H. Rowan III, Matthew J. Campen, Lindsay B. Wichers, William P. Watkinson

Published in: Cardiovascular Toxicology | Issue 1/2007

Login to get access

Abstract

Heart rate variability (HRV) is a measure of cardiac pacing dynamics that has recently garnered a great deal of interest in environmental health studies. While the use of these measures has become popular, much uncertainty remains in the interpretation of results, both in terms of human and animal research. In humans, HRV endpoints, specifically chronic alterations in baseline HRV patterns, have been reasonably well characterized as prognostic indicators of adverse outcomes for a variety of diseases. However, such information is lacking for reversible HRV changes that may be induced by short-term exposures to environmental toxicants. Furthermore, there are minimal substantive data, either acute or chronic, regarding the pathological interpretation or prognostic value of toxicant-induced changes in HRV in rodents. The present report summarizes the physiological and clinical aspects of HRV, the methodological processes for obtaining these endpoints, and previous human and animal studies in the field of environmental health. Furthermore, we include a discussion of important caveats and recommendations for the interpretation of HRV data in animal research.
Literature
1.
Hon, E. H., & Lee, S. T. (1963). The fetal electrocardiogram. I The electrocardiogram of the dying fetus. American Journal of Obstetrics and Gynecology, 87, 804–813.PubMed
2.
Magari, S. R., Schwartz, J., Williams, P. L., Hauser, R., Smith T. J., & Christiani, D. C. (2002). The association of particulate air metal concentrations with heart rate variability. Environmental Health Perspectives, 110, 875–880.PubMed
3.
Schwartz, J., Litonjua, A., Suh, H., Verrier, M., Zanobetti, A., Syring, M., Nearing, B., Verrier, R., Stone, P., MacCallum, G., Speizer, F. E., & Gold, D. R. (2005). Traffic related pollution and heart rate variability in a panel of elderly subjects. Thorax, 60, 455–461.PubMed
4.
de Paula Santos, U., Braga, A. L., Giorgi, D. M., Pereira, L. A., Grupi, C. J., Lin, C. A., Bussacos, M. A., Zanetta, D. M., do Nascimento Saldiva, P. H., & Filho, M. T. (2005). Effects of air pollution on blood pressure and heart rate variability: A panel study of vehicular traffic controllers in the city of Sao Paulo, Brazil. European Heart Journal, 26, 193–200.PubMed
5.
Liao, D., Duan, Y., Whitsel, E. A., Zheng, Z. J., Heiss, G., Chinchilli, V. M., & Lin, H. M. (2004). Association of higher levels of ambient criteria pollutants with impaired cardiac autonomic control: A population-based study. American Journal of Epidemiology, 159, 768–777.PubMed
6.
Holguin, F., Tellez-Rojo, M. M., Hernandez, M., Cortez, M., Chow J. C., Watson, J. G., Mannino, D., & Romieu, I. (2003). Air pollution and heart rate variability among the elderly in Mexico City. Epidemiology, 14, 521–527.PubMed
7.
Tarkiainen, T. H., Timonen, K. L., Vanninen, E. J., Alm, S., Hartikainen, J. E., & Pekkanen, J. (2003). Effect of acute carbon monoxide exposure on heart rate variability in patients with coronary artery disease. Clinical Physiology Functional Imaging, 23, 98–102.
8.
Pope, C. A. 3rd, Verrier, R. L., Lovett, E. G., Larson, A. C., Raizenne, M. E., Kanner, R. E., Schwartz, J., Villegas, G. M., Gold D. R., & Dockery, D. W. (1999). Heart rate variability associated with particulate air pollution. American Heart Journal, 138, 890–899.PubMed
9.
Liao, D., Creason, J., Shy, C., Williams, R., Watts, R., & Zweidinger, R. (1999). Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environmental Health Perspectives, 107, 521–525.PubMed
10.
Corey, L. M., Baker, C., & Luchtel, D. L. (2006). Heart-rate variability in the apolipoprotein E knockout transgenic mouse following exposure to Seattle particulate matter. Journal of Toxicology and Environmental Health A, 69, 953–965.
11.
Wellenius, G. A., Saldiva, P. H., Batalha, J. R., Krishna Murthy G. G., Coull, B. A., Verrier, R. L., & Godleski, J. J. (2002). Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction. Toxicological Sciences, 66, 327–335.PubMed
12.
Rivero, D. H., Soares, S. R., Lorenzi-Filho, G., Saiki, M., Godleski, J. J., Antonangelo, L., Dolhnikoff, M., & Saldiva, P.H (2005). Acute cardiopulmonary alterations induced by fine particulate matter of Sao Paulo, Brazil. Toxicological Sciences, 85, 898–905.PubMed
13.
Harder, V., Gilmour, P., Lentner, B., Karg, E., Takenaka, S., Ziesenis, A., Stampfl, A., Kodavanti, U., Heyder, J., & Schulz, H. (2005). Cardiovascular responses in unrestrained WKY rats to inhaled ultrafine carbon particles. Inhalation Toxicology, 17, 29–42.PubMed
14.
Chen, L. C., & Hwang, J. S. (2005). Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. IV Characterization of acute and chronic effects of ambient air fine particulate matter exposures on heart-rate variability. Inhalation Toxicology, 17, 209–216.PubMed
15.
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. (1996). Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. European Heart Journal, 17, 354–381.
16.
Schwartz, J., Park, S. K., O’Neill, M. S., Vokonas, P. S., Sparrow D., Weiss, S., & Kelsey, K. (2005). Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles: Gene-by-drug-by-environment interaction. American Journal of Respiratory and Critical Care Medicine, 172, 1529–1533.PubMed
17.
Delfino, R. J., Sioutas, C., & Malik, S. (2005). Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environmental Health Perspectives, 113, 934–946.PubMed
18.
Zareba, W., Nomura, A., & Couderc, J. P. (2001). Cardiovascular effects of air pollution: What to measure in ECG? Environmental Health Perspectives, 109(Suppl 4), 533–538.PubMed
19.
Timonen, K. L., Vanninen, E., de Hartog, J., Ibald-Mulli, A., Brunekreef, B., Gold, D. R., Heinrich, J., Hoek, G., Lanki, T., Peters, A., Tarkiainen, T., Tiittanen, P., Kreyling, W., & Pekkanen, J. (2005). Effects of ultrafine and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery disease: The ULTRA study. Journal of Exposure Analysis and Environmental Epidemiology, 16(4), 332-341.
20.
Vermylen, J., Nemmar, A., Nemery, B., Hoylaerts, M. F. (2005) Ambient air pollution and acute myocardial infarction. Journal of Thrombosis and Thrombolysis 3, 1955–1961.
21.
Dockery, D. W. (2001). Epidemiologic evidence of cardiovascular effects of particulate air pollution. Environmental Health Perspectives, 109 (Suppl 4), 483–486.PubMed
22.
Pope, C. A. 3rd (2000). What do epidemiologic findings tell us about health effects of environmental aerosols? Journal of Aerosol Medicine, 13, 335–354.PubMed
23.
Brook, R. D., Franklin, B., Cascio, W., Hong, Y., Howard, G., Lipsett, M., Luepker, R., Mittleman, M., Samet, J., Smith, S. C. Jr, & Tager, I. (2004). Air pollution and cardiovascular disease: A statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation, 109, 2655–2671.PubMed
24.
Peters, A. (2005). Particulate matter and heart disease: Evidence from epidemiological studies. Toxicology and Applied Pharmacology, 207, 477–482.PubMed
25.
Bhatnagar, A. (2004). Cardiovascular pathophysiology of environmental pollutants. American Journal of Physiology-Heart and Circulatory Physiology, 286, H479–485PubMed
26.
Schwartz, J., & Morris, R. (1995). Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. American Journal of Epidemiology, 142, 23–35.PubMed
27.
Samet, J. M., Dominici, F., Curriero, F. C., Coursac, I., & Zeger, S. L. (2000). Fine particulate air pollution and mortality in 20 US cities, 1987–1994. New England Journal of Medicine, 343, 1742–1749.PubMed
28.
Peters, A., Liu, E., Verrier, R. L., Schwartz, J., Gold, D. R., Mittleman, M., Baliff, J., Oh, J. A., Allen, G., Monahan, K., & Dockery, D. W. (2000). Air pollution and incidence of cardiac arrhythmia. Epidemiology, 11, 11–17.PubMed
29.
Watkinson, W. P., Campen, M. J., Lyon, J. Y., Highfill, J. W., Wiester, M. J., & Costa, D. L. (1997). Impact of the hypothermic response in inhalation toxicology studies. Annals of the New York Academy of Sciences, 813, 849–863.PubMed
30.
Watkinson, W. P., Campen, M. J., & Costa, D. L. (1998). Cardiac arrhythmia induction after exposure to residual oil fly ash particles in a rodent model of pulmonary hypertension. Toxicological Science, 41, 209–216.
31.
Watkinson, W. P., Campen, M. J., Nolan, J. P., & Costa, D.L (2001). Cardiovascular and systemic responses to inhaled pollutants in rodents: Effects of ozone and particulate matter. environ health perspect, 109 (Suppl 4), 539–546.PubMed
32.
Wichers, L. B., Nolan, J. P., Winsett, D. W., Ledbetter, A. D., Kodavanti, U. P., Schladweiler, M. C., Costa, D. L., & Watkinson, W.P (2004). Effects of instilled combustion-derived particles in spontaneously hypertensive rats. Part I: Cardiovascular responses. Inhalation Toxicology, 16, 391–405.PubMed
33.
Watkinson, W. P., Campen, M. J., Wichers, L. B., Nolan, J. P., & Costa, D. L. (2003). Cardiac and thermoregulatory responses to inhaled pollutants in healthy and compromised rodents: Modulation via interaction with environmental factors. Environmental Research, 92, 35–47.PubMed
34.
Campen, M. J., Nolan, J. P., Schladweiler, M. C., Kodavanti, U. P., Costa, D. L., & Watkinson, W. P. (2002). Cardiac and thermoregulatory effects of instilled particulate matter-associated transition metals in healthy and cardiopulmonary-compromised rats. Journal of Toxicology and Environmental Health A, 65, 1615–1631.
35.
Watkinson, W. P., & Gordon, C. J. (1993). Caveats regarding the use of the laboratory rat as a model for acute toxicological studies: Modulation of the toxic response via physiological and behavioral mechanisms. Toxicology, 81, 15–31.PubMed
36.
Vassalle, M., Zhang, H. (2001). On the mechanisms of cholinergic control of the sinoatrial node discharge. Journal of Cardiovascular Pharmacology, 37, 173–186.PubMed
37.
Jokkel, G., Bonyhay, I., & Kollai, M. (1995). Heart rate variability after complete autonomic blockade in man. Journal of the Autonomic Nervous System, 51, 85–89.PubMed
38.
Japundzic, N., Grichois, M.-L., Zitoun, P., Laude, D., & Elghozi, J.-L. (1990). Spectral analysis of blood pressure and heart rate in conscious rats: effects of autonomic blockers. Journal of the Autonomic Nervous System, 30, 91–100.PubMed
39.
Cerutti, C., Gustin, M. P., Paultre, C. Z., Lo, M., Julien, C., Vincent, M., & Sassard, J. (1991). Autonomic nervous system and cardiovascular variability in rats: A spectral analysis approach. American Journal of Physiology, 261, H1292–H1299.PubMed
40.
Kuwahara, M., Yayou, K., Ishii, K., Hashimoto, S., Tsubone, H., & Sugano, S. (1994). Power spectral analysis of heart rate variability as a new method for assessing autonomic activity in the rat. Journal of Electrocardiology, 27, 333–337.PubMed
41.
Aubert, A. E., Ramaekers, D., Beckers, F., Breem, R., Denef, C., van de Werf, F., & Ector, H. (1999). The analysis of heart rate variability in unrestrained rats. Validation of method and results. Computer Methods and Programs in Biomedicine, 60, 197–213.PubMed
42.
Hashimoto, M., Kuwahara, M., Tsubone, H., & Sugano, S. (1999). Diurnal variation of autonomic nervous activity in the rat: Investigation by power spectral analysis of heart rate variability. Journal of Electrocardiology, 32, 167–171.PubMed
43.
Cohen, M. A., & Taylor, J. A. (2002). Short-term cardiovascular oscillations in man: measuring and modelling the physiologies. Journal of Physiology, 542, 669–683.PubMed
44.
Malliani, A., Pagani, M., Lombardi, F., & Cerutti, S. (1991) Cardiovascular neural regulation explored in the frequency domain. Circulation, 84, 482–492.PubMed
45.
Malpas, S. C. (2002). Neural influences on cardiovascular variability: Possibilities and pitfalls. American Journal of Physiology-Heart and Circulatory Physiology, 282, H6–H20.PubMed
46.
Stauss, H. M. (2003). Heart rate variability. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 285, R927–931.
47.
Stein, P. K., & Kleiger, R. E. (1999). Insights from the study of heart rate variability. Annual Review of Medicine, 50, 249–261.PubMed
48.
Gang, Y., & Malik, M. (2002). Heart rate variability in critical care medicine. Current Opinion in Critical Care, 8, 371–375.PubMed
49.
Pumprla, J., Howorka, K., Groves, D., Chester, M., & Nolan, J. (2002). Functional assessment of heart rate variability: Physiological basis and practical applications. International Journal of Cardiology, 84, 1–14.PubMed
50.
Beckers, F., Ramaekers, D., Speijer, G., Ector, H., Vanhaecke J., Verheyden, B., Van Cleemput, J., Droogne, W., Van de Werf, F., & Aubert, A. E. (2004). Different evolutions in heart rate variability after heart transplantation: 10-year follow-up. Transplantation, 78, 1523–1531.PubMed
51.
Goldberger, A. L. (2006). Giles f. Filley lecture. Complex systems. Proceedings of the American Thoracic Society, 3, 467–471.PubMed
52.
Baudrie, V., Tulen, J. H., Blanc, J., & Elghozi, J. L. (1997). Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats. Journal of Autonomic Pharmacology, 17, 303–309.PubMed
53.
Takeuchi, H., Enzo, A., & Minamitani, H. (2001). Circadian rhythm changes in heart rate variability during chronic sound stress. Medical & Biological Engineering Computing, 39,113–117.
54.
Yang, C. C. H., Shaw, F.-Z., Lai, C. J., Lai, C.-W., & Kuo, T. B. J (2003). Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in rats. Neuroscience Letters, 336, 21–24.PubMed
55.
Campen, M. J., Tagaito, Y., Li, J., Balbir, A., Tankersley, C. G., Smith, P., Schwartz, A., & O’Donnell, C. P. (2004). Phenotypic variation in cardiovascular responses to acute hypoxic and hypercapnic exposure in mice. Physiol Genomics, 20, 15–20.PubMed
56.
Moody, G. B. (1992). ECB-based indices of physical activity. IEEE Computer Cardiology, 19, 403–406.
57.
Jasson, S., Medigue, C., Maison-Blanche, P., Montano, N., Meyer L., Vermeiren, C., Mansier, P., Coumel, P., Malliani, A., & Swynghedauw, B. (1997). Instant power spectrum analysis of heart rate variability during orthostatic tilt using a time-/frequency-domain method. Circulation, 96, 3521–3526.PubMed
58.
Pereira de Souza Neto, E., Custaud, M., Somody, L., & Gharib, C. (2001). Assessment of autonomic cardiovascular indices in non-stationary data in rats. Comparative Biochemistry and Physiology A-Molecular and Integrative Physiology, 128, 105–115.
59.
Rubini, R., Porta, A., Baselli, G., Cerutti, S., & Paro, M. (1993). Power spectrum analysis of cardiovascular variability monitored by telemetry in conscious unrestrained rats. Journal of the Autonomic Nervous System, 45, 181–190.PubMed
60.
Mansier, P., Medigue, C., Charlotte, N., Vermeiren, C., Coraboeuf, E., Deroubai, E., Ratner, E., Chevalier, B., Clairambault, J., Carre, F., Dahkli, T., Bertin, B., Briand, P., Strosberg, D., & Swynghedauw, B. (1996). Decreased heart rate variability in transgenic mice overexpressing atrial beta 1-adrenoceptors. American Journal of Physiology, 271, H1465–H1472.PubMed
61.
Mansier, P., Clairambault, J., Charlotte, N., Medigue, C., Vermeiren, C., LePape, G., Carre, F., Gounaropoulou, A., & Swynghedauw, B. (1996). Linear and non-linear analyses of heart rate variability: A minireview. Cardiovascular Research, 31, 371–379.PubMed
62.
Pereira de Souza Neto, E., Custaud, M. A., Frutoso, J., Somody L., Gharib, C., & Fortrat, J. O. (2001). Smoothed pseudo Wigner-Ville distribution as an alternative to Fourier transform in rats. Autonomic Neuroscience, 87, 258–267.
63.
Akselrod, S., Eliash, S., Oz, O., & Cohen, S. (1987). Hemodynamic regulation in SHR: Investigation by spectral analysis. American Journal of Physiology, 253, H176–H183.PubMed
64.
Dunlap, E. D., Samols, E., Waite, L. C., & Pfeifer, M. A. (1987). Development of a method to determine autonomic nervous system function in the rat. Metabolism, 36, 193–197.PubMed
65.
Ferrari, A. U., Daffonchio, A., Albergati, F., & Mancia, G. (1987). Inverse relationship between heart rate and blood pressure variabilities in rats. Hypertension, 10, 533–537.PubMed
66.
Murphy, C. A., Sloan, R. P., & Myers, M. M. (1991). Pharmacologic responses and spectral analyses of spontaneous fluctuations in heart rate and blood pressure in SHR rats. Journal of the Autonomic Nervous System, 36, 237–250.PubMed
67.
Baselli, G., & Cerutti, S. (1985). Identification techniques applied to processing of signals from cardiovascular systems. Medical Informatics (London) 10, 223–235.CrossRef
68.
Pagani, M., Lombardi, F., Guzzetti, S., Rimoldi, O., Furlan, R., Pizzinelli, P., Sandrone, G., Malfatto, G., Dell’Orto, S., & Piccaluga, E., et al. (1986). Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circulation Research, 59, 178–193.PubMed
69.
Boardman, A., Schlindwein, F. S., Rocha, A. P., & Leite, A. (2002). A study on the optimum order of autoregressive models for heart rate variability. Physiological Measurement, 23, 325–336.PubMed
70.
Tankersley, C. G., Campen, M., Bierman, A., Flanders, S. E., Broman, K. W., & Rabold, R. (2004). Particle effects on heart-rate regulation in senescent mice. Inhalation Toxicology, 16, 381–390.PubMed
71.
Campen, M. J., Tagaito Y., Jenkins, T. P., Balbir, A., & O’Donnell, C. P. (2005). Heart rate variability responses to hypoxic and hypercapnic exposures in different mouse strains. Journal of Applied Physiology, 99, 807–813.PubMed
72.
Pinna, G. D., Maestri, R., Di Cesare, A., Colombo, R., & Minuco, G. (1994). The accuracy of power-spectrum analysis of heart-rate variability from annotated RR lists generated by Holter systems. Physiological Measurement, 15, 163–179.PubMed
73.
Perlini, S., Giangregorio, F., Coco, M., Radaelli, A., Solda, P. L., Bernardi, L., & Ferrari, A. U. (1995). Autonomic and ventilatory components of heart rate and blood pressure variability in freely behaving rats. American Journal of Physiology, 269, H1729–1734.PubMed
74.
Furlan, R., Guzzetti, S., Crivellaro, W., Dassi, S., Tinelli M., Baselli, G., Cerutti, S., Lombardi, F., Pagani, M., & Malliani, A. (1990). Continuous 24-h assessment of the neural regulation of systemic arterial pressure and RR variabilities in ambulant subjects. Circulation, 81, 537–547.PubMed
75.
Baselli, G., Cerutti, S., Civardi, S., Malliani, A., & Pagani, M. (1988). Cardiovascular variability signals: Towards the identification of a closed-loop model of the neural control mechanisms. IEEE Transactions on Biomedical Engineering, 35, 1033–1046.PubMed
76.
Just, A., Faulhaber, J., & Ehmke, H. (2000). Autonomic cardiovascular control in conscious mice. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 279, R2214–R2221.
77.
Gehrmann, J., Hammer, P. E., Maguire, C. T., Wakimoto, H., Triedman, J. K., & Berul, C. I. (2000). Phenotypic screening for heart rate variability in the mouse. American Journal of Physiology-Heart and Circulatory Physiology, 279, H733–H740.PubMed
78.
Swynghedauw, B., Jasson, S., Clairambault, J., Chevalier, B., Heymes, C., Medigue, C., Carre, F., & Mansier, P. (1997). Myocardial determinants in regulation of the heart rate. Journal of Molecular Medicine, 75, 860–866.PubMed
79.
Routledge, H. C., Chowdhary, S., & Townend, J. N. (2002). Heart rate variability–a therapeutic target? Journal of Clinical Pharmacy and Therapeutics, 27, 85–92.PubMed
80.
Kass, D. A., Hare, J. M., & Georgakopoulos, D. (1998). Murine cardiac function: A cautionary tail. Circulation Research, 82, 519–522.PubMed
81.
Towa, S., Kuwahara, M., & Tsubone, H. (2004). Characteristics of autonomic nervous function in Zucker-fatty rats: Investigation by power spectral analysis of heart rate variability. Experimental Animals, 53, 137–144.PubMed
82.
Hashimoto, M., Harada, T., Ishikawa, T., Obata, M., & Shibutani, Y. (2001). Investigation on diabetic autonomic neuropathy assessed by power spectral analysis of heart rate variability in WBN/Kob rats. Journal of Electrocardiology, 34, 243–250.PubMed
83.
De Angelis, K., Schaan, B. D., Maeda, C. Y., Dall’Ago P., Wichi, R. B., & Irigoyen, M. C. (2002). Cardiovascular control in experimental diabetes. Brazilian Journal of Medical and Biological Research, 35, 1091–1100.PubMed
84.
Schaan, B. D., Maeda, C. Y., Timm, H. B., Medeiros, S., Moraes R. S., Ferlin, E., Fernandes, T. G., Ribeiro, J. P., Schmid, H., & Irigoyen, M. C. (1997). Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin. Brazilian Journal of Medical and Biological Research, 30, 1081–1086.PubMed
85.
Howarth, F. C., Jacobson, M., Shafiullah, M., & Adeghate, E. (2005). Long-term effects of streptozotocin-induced diabetes on the electrocardiogram, physical activity and body temperature in rats. Experimental Physiology, 90, 827–835.PubMed
86.
Howarth, F. C., Jacobson, M., Shafiullah, M., & Adeghate, E. (2006). Effects of insulin treatment on heart rhythm, body temperature and physical activity in streptozotocin-induced diabetic rat. Clinical and Experimental Pharmacology and Physiology, 33, 327–331.PubMed
87.
Das, S., & O’Keefe, J. H. (2006). Behavioral cardiology: recognizing and addressing the profound impact of psychosocial stress on cardiovascular health. Current Atherosclerosis Reports, 8, 111–118.PubMed
88.
Curtis, B. M., & O’Keefe, J. H. Jr. (2002). Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clinic Proceedings, 77, 45–54.PubMedCrossRef
89.
Sgoifo, A., Koolhaas, J., De Boer, S., Musso, E., Stilli, D., Buwalda, B., & Meerlo, P. (1999). Social stress, autonomic neural activation, and cardiac activity in rats. Neuroscience & Biobehavioral Reviews, 23, 915–923.
90.
Sgoifo, A., Koolhaas, J. M., Musso, E., & De Boer, S. F. (1999). Different sympathovagal modulation of heart rate during social and nonsocial stress episodes in wild-type rats. Physiology & Behavior, 67, 733–738.
91.
Sgoifo, A., Pozzato, C., Costoli, T., Manghi, M., Stilli, D., Ferrari, P. F., Ceresini, G., & Musso, E. (2001). Cardiac autonomic responses to intermittent social conflict in rats. Physiology & Behavior, 73, 343–349.
92.
Sgoifo, A., Buwalda, B., Roos, M., Costoli, T., Merati, G., & Meerlo, P. (2006). Effects of sleep deprivation on cardiac autonomic and pituitary-adrenocortical stress reactivity in rats. Psychoneuroendocrinology, 31, 197–208.PubMed
93.
Inagaki, H., Kuwahara, M., & Tsubone, H. (2004). Effects of psychological stress on autonomic control of heart in rats. Experimental Animals, 53, 373–378.PubMed
94.
Inagaki, H., Kuwahara, M., & Tsubone, H. (2005). Changes in autonomic control of heart associated with classical appetitive conditioning in rats. Experimental Animals, 54, 61–69.PubMed
95.
Grippo, A. J., Moffitt, J. A., & Johnson, A. K. (2002) Cardiovascular alterations and autonomic imbalance in an experimental model of depression. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 282, R1333–R1341.
96.
Grippo, A. J., Beltz, T. G., & Johnson, A. K. (2003). Behavioral and cardiovascular changes in the chronic mild stress model of depression. Physiology & Behavior, 78, 703–710.
97.
Nijsen, M. J., Croiset, G., Diamant, M., Stam, R., Delsing, D., de Wied, D., & Wiegant, V. M. (1998). Conditioned fear-induced tachycardia in the rat: Vagal involvement. European Journal of Pharmacology, 350, 211–222.PubMed
98.
Grippo, A. J., Santos, C. M., Johnson, R. F., Beltz, T. G., Martins, J. B., Felder, R. B., & Johnson, A. K. (2004). Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression. American Journal of Physiology-Heart and Circulatory Physiology, 286, H619–H626.PubMed
99.
Cohen, H., & Zohar, J. (2004). An animal model of posttraumatic stress disorder: The use of cut-off behavioral criteria. Annals of the New York Academy of Sciences, 1032, 167–178.PubMed
100.
Pope, C. A. 3rd, Burnett, R. T., Thurston, G. D., Thun, M. J., Calle, E. E., Krewski, D., & Godleski, J. J. (2004). Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation, 109, 71–77.PubMed
101.
Dominici, F., Peng, R. D., Bell, M. L., Pham, L., McDermott, A., Zeger, S. L., & Samet, J. M. (2006). Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. Jama, 295, 1127–1134.PubMed
102.
Gong, H., Linn, W. S., Terrell, S. L., Anderson, K. R., Clark K. W., Sioutas, C., Cascio, W. E., Alexis, N., & Devlin, R. B. (2004). Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution. Inhalation Toxicology, 16, 731–744.PubMed
103.
Campen, M. J., Tagaito, Y., Jenkins, T. P., Balbir, A., & O’Donnell, C. P. (2005). Heart rate variability responses to hypoxic and hypercapnic exposures in different mouse strains. Journal of Applied Physiology, 99, 807–813.PubMed
104.
Kodavanti, U. P., Moyer, C. F., Ledbetter, A. D., Schladweiler M. C., Costa, D. L., Hauser, R., Christiani, D. C., & Nyska, A. (2003). Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat. Toxicological Sciences, 71, 237–245.PubMed
105.
Elder, A. C., Gelein, R., Azadniv, M., Frampton, M., Finkelstein, J., & Oberdorster, G. (2004). Systemic effects of inhaled ultrafine particles in two compromised, aged rat strains. Inhalation Toxicology, 16, 461–471.PubMed
106.
Lippmann, M., Gordon, T., & Chen, L. C. (2005). Effects of subchronic exposures to concentrated ambient particles in mice. IX Integral assessment and human health implications of subchronic exposures of mice to CAPs. IX Integral assessment and human health implications of subchronic exposures of mice to CAPs. Inhalation Toxicology, 17, 255–261.PubMed
107.
Habler, H. J., Janig, W., & Michaelis, M. (1994). Respiratory modulation in the activity of sympathetic neurones. Progress in Neurobiology, 43, 567–606.PubMed
108.
Malik, M., & Camm, A. J. (1993). Components of heart rate variability—what they really mean and what we really measure. American Journal of Cardiology, 72, 821–822.PubMed
109.
Rentero, N., Cividjian, A., Trevaks, D., Pequignot, J. M., Quintin, L., & McAllen, R. M. (2002). Activity patterns of cardiac vagal motoneurons in rat nucleus ambiguus. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 283, R1327–R1334.
110.
Tzeng, Y.-C., Galletly, D. C., & Larsen, P. D. (2005) Paradoxical respiratory sinus arrhythmia in the anesthetized rat. Autonomic Neuroscience, 118, 25–31.PubMed
111.
Bouairi, E., Neff, R., Evans, C., Gold, A., Andresen, M. C., & Mendelowitz, D. (2004). Respiratory sinus arrhythmia in freely moving and anesthetized rats. Journal of Applied Physiology, 97, 1431–1436.PubMed
112.
Neff, R. A., Wang, J., Baxi, S., Evans, C., & Mendelowitz, D. (2003). Respiratory sinus arrhythmia: Endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons. Circulation Research, 93, 565–572.PubMed
113.
Jose, A. D. (1966). Effect of combined sympathetic and parasympathetic blockade on heart rate and cardiac function in man. American Journal of Cardiology, 18, 476–478.PubMed
114.
Wickman, K., Nemec, J., Gendler, S. J., & Clapham, D. E. (1998) Abnormal heart rate regulation in GIRK4 knockout mice. Neuron, 20, 103–114.PubMed
115.
Georgakopoulos, D., & Kass, D. (2001). Minimal force-frequency modulation of inotropy and relaxation of in situ murine heart. Journal of Physiology, 534, 535–545.PubMed
116.
Langer, S. F., Lambertz, M., Langhorst, P., & Schmidt, H.D (1999). Interbeat interval variability in isolated working rat hearts at various dynamic conditions and temperatures. Research in Experimental Medicine (Berl) 199, 1–19.
117.
Bastille, A. M., Matthew, C. B., Gonzalez, R. R., Sils, I. V., & Hoyt, R. W. (2004). Application of heart rate variability to determine physiologic changes in hypothermic rats. Journal of Thermal Biology, 29, 237–243.
118.
Matthew, C. B., Bastille, A. M., Gonzalez, R. R., & Sils, I. V. (2002). Heart rate variability and electrocardiogram waveform as predictors of morbidity during hypothermia and rewarming in rats Canadian Journal of Physiology and Pharmacology, 80, 925–933.PubMed
119.
Brauer, M., Ebelt, S. T., Fisher, T. V., Brumm, J., Petkau, A. J., & Vedal, S. (2001). Exposure of chronic obstructive pulmonary disease patients to particles: Respiratory and cardiovascular health effects. Journal of Exposure Analysis and Environmental Epidemiology, 11, 490–500.PubMed
120.
Chan, C. C., Chuang, K. J., Shiao, G. M., & Lin, L. Y. (2004) Personal exposure to submicrometer particles and heart rate variability in human subjects. Environmental Health Perspectives, 112, 1063–1067.PubMed
121.
Chuang, K. J., Chan, C. C., Chen, N. T., Su, T. C., & Lin, L. Y. (2005). Effects of particle size fractions on reducing heart rate variability in cardiac and hypertensive patients. Environmental Health Perspectives, 113, 1693–1697.PubMed
122.
Creason, J., Neas, L., Walsh, D., Williams, R., Sheldon, L., Liao, D., & Shy, C. (2001). Particulate matter and heart rate variability among elderly retirees: the Baltimore 1998 PM study. J Expo Anal Environ Epidemiol 11, 116–122.PubMed
123.
Devlin, R. B., Ghio, A. J., Kehrl, H., Sanders, G., & Cascio, W. (2003). Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability. European Respiratory Journal Suppl, 40, 76s–80s.PubMed
124.
Ebelt, S. T., Wilson, W. E., & Brauer, M. (2005). Exposure to ambient and nonambient components of particulate matter: A comparison of health effects. Epidemiology, 16, 396–405.PubMed
125.
Eninger, R. M., & Rosenthal, F. S. (2004). Heart rate variability and particulate exposure in vehicle maintenance workers: A pilot study. Journal of Occupational and Environmental Hygienic, 1, 493–499.
126.
Gold, D. R., Litonjua, A., Schwartz, J., Lovett, E., Larson, A., Nearing, B., Allen, G., Verrier, M., Cherry, R., & Verrier, R. (2000). Ambient pollution and heart rate variability. Circulation, 101, 1267–1273.PubMed
127.
Gong, H. Jr., Linn, W. S., Sioutas, C., Terrell, S. L., Clark, K. W., Anderson, K. R., & Terrell, L. L. (2003). Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in Los Angeles. Inhalation Toxicology, 15, 305–325.PubMed
128.
Gong, H., Jr., Linn, W. S., Terrell, S. L., Clark, K. W., Geller, M. D., Anderson, K. R., Cascio, W. E., & Sioutas, C. (2004). Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicology, 16, 335–343.PubMed
129.
Magari, S. R., Hauser, R., Schwartz, J., Williams, P. L., Smith, T. J., & Christiani, D. C. (2001). Association of heart rate variability with occupational and environmental exposure to particulate air pollution. Circulation, 104, 986–991.PubMed
130.
Magari, S. R., Schwartz, J., Williams, P. L., Hauser, R., Smith T. J., & Christiani, D. C. (2002). The association between personal measurements of environmental exposure to particulates and heart rate variability. Epidemiology, 13, 305–310.PubMed
131.
Park, S. K., O’Neill M. S., Vokonas, P. S., Sparrow, D., & Schwartz, J. (2005). Effects of air pollution on heart rate variability: The VA normative aging study. Environmental Health Perspectives, 113, 304–309.PubMed
132.
Pope, C. A. 3rd, Eatough, D. J., Gold, D. R., Pang, Y., Nielsen, K. R., Nath, P., Verrier, R. L., & Kanner, R. E. (2001). Acute exposure to environmental tobacco smoke and heart rate variability. Environmental Health Perspectives, 109, 711–716.PubMed
133.
Pope, C. A. 3rd, Hansen, M. L., Long, R. W., Nielsen, K. R., Eatough, N. L., Wilson, W. E., & Eatough, D. J. (2004). Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. Environmental Health Perspectives, 112, 339–345.PubMed
134.
Riediker, M., Devlin, R. B., Griggs, T. R., Herbst, M. C., Bromberg, P. A., Williams, R. W., & Cascio, W. E. (2004) Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions. Part Fibre Toxicology, 1, 2.
135.
Riediker, M., Herbst, M. C., Devlin, R. B., Griggs, T. R., Bromberg, P. A., & Cascio, W. E. (2005). Effect of the September 11, 2001 terrorist attack on a state highway patrol trooper’s heart rate variability. Annals of Noninvasive Electrocardiology, 10, 83–85.PubMed
136.
Riojas-Rodriguez, H., Escamilla-Cejudo, J. A., Gonzalez-Hermosillo, J. A., Tellez-Rojo, M. M., Vallejo, M., Santos-Burgoa, C., & Rojas-Bracho, L. (2006). Personal PM2.5 and CO exposures and heart rate variability in subjects with known ischemic heart disease in Mexico City. Journal of Exposure Analysis and Environmental Epidemiology, 16, 131–137.
137.
Romieu, I., Tellez-Rojo, M. M., Lazo, M., Manzano-Patino, A., Cortez-Lugo, M., Julien, P., Belanger, M. C., Hernandez-Avila, M., & Holguin, F. (2005). Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter. American Journal of Respiratory and Critical Care Medicine, 172, 1534–1540.PubMed
138.
Routledge, H. C., Manney, S., Harrison, R. M., Ayres, J. G., & Townend, J. N. (2006). Effect of inhaled sulphur dioxide and carbon particles on heart rate variability and markers of inflammation and coagulation in human subjects. Heart 92, 220–227.PubMed
139.
Sullivan, J. H., Schreuder, A. B., Trenga, C. A., Liu, S. L., Larson, T. V., Koenig, J. Q., & Kaufman, J. D. (2005). Association between short term exposure to fine particulate matter and heart rate variability in older subjects with and without heart disease. Thorax, 60, 462–466.PubMed
140.
Tunnicliffe, W. S., Hilton, M. F., Harrison, R. M., & Ayres, J. G. (2001). The effect of sulphur dioxide exposure on indices of heart rate variability in normal and asthmatic adults. European Respiratory Journal, 17, 604–608.PubMed
141.
Vallejo, M., Ruiz, S., Hermosillo, A. G., Borja-Aburto, V. H., & Cardenas, M. (2006). Ambient fine particles modify heart rate variability in young healthy adults. Journal of Exposure Analysis and Environmental Epidemiology, 16, 125–130.
142.
Wheeler, A., Zanobetti, A., Gold, D. R., Schwartz, J., Stone, P., & Suh, H. H. (2006). The relationship between ambient air pollution and heart rate variability differs for individuals with heart and pulmonary disease. Environmental Health Perspectives, 114, 560–566.PubMedCrossRef
143.
Godleski, J. J., Verrier, R. L., Koutrakis, P., Catalano, P., Coull, B., Reinisch, U., Lovett, E. G., Lawrence, J., Murthy, G. G., Wolfson, J. M., Clarke, R. W., Nearing, B. D., & Killingsworth, C. (2000). Mechanisms of morbidity and mortality from exposure to ambient air particles. Research Report (Health Effects Institute) 5–88; discussion 89–103.
144.
Lippmann, M., Hwang, J. S., Maciejczyk, P., & Chen, L. C. (2005). PM source apportionment for short-term cardiac function changes in ApoE-/- mice. Environmental Health Perspectives, 113, 1575–1579.PubMed
145.
Nurkiewicz, T. R., Porter, D. W., Barger, M., Castranova, V., & Boegehold, M. A. (2004). Particulate matter exposure impairs systemic microvascular endothelium-dependent dilation. Environmental Health Perspectives, 112, 1299–1306.PubMed
146.
Tankersley, C. G., Irizarry, R., Flanders, S. E., Rabold, R., & Frank, R. (2003). Unstable heart rate and temperature regulation predict mortality in AKR/J mice. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 284, R742–750.
147.
Sun, Q., Wang, A., Jin, X., Natanzon, A., Duquaine, D., Brook R. D., Aguinaldo, J. G., Fayad, Z. A., Fuster, V., Lippmann, M., Chen, L. C., & Rajagopalan, S. (2005). Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA, 294, 3003–3010.PubMed
148.
Huikuri, H. V., Jokinen, V., Syvanne, M., Nieminen, M. S., Airaksinen, K. E., Ikaheimo, M. J., Koistinen, J. M., Kauma, H., Kesaniemi, A. Y., Majahalme, S., Niemela, K. O., & Frick, M. H. (1999). Heart rate variability and progression of coronary atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology, 19, 1979–1985.
149.
McDonald, J. D., Eide, I., Seagrave, J., Zielinska, B., Whitney K., Lawson, D. R., & Mauderly, J. L. (2004). Relationship between composition and toxicity of motor vehicle emission samples. Environmental Health Perspectives, 112, 1527–1538.PubMed
150.
Rhoden, C. R., Wellenius, G. A., Ghelfi, E., Lawrence, J., & Gonzalez-Flecha, B. (2005). PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation. Biochimica et Biophysica Acta, 1725, 305–313.PubMed
151.
Melin, A., Bonnet, P., Eder, V., Antier, D., Obert, P., & Fauchier, L. (2005). Direct implication of carbon monoxide in the development of heart failure in rats with cardiac hypertrophy subjected to air pollution. Cardiovascular Toxicology, 5, 311–320.PubMed
152.
Sandercock, G. R., Bromley, P. D., & Brodie, D. A. (2005). The reliability of short-term measurements of heart rate variability. International Journal of Cardiology, 103, 238–247.PubMed
Metadata
Title
Heart rate variability in rodents: uses and caveats in toxicological studies
Authors
William H. Rowan III
Matthew J. Campen
Lindsay B. Wichers
William P. Watkinson
Publication date
01-03-2007
Publisher
Humana Press Inc
Published in
Cardiovascular Toxicology / Issue 1/2007
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-007-0004-6

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits