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Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 6, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn150
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

The Circadian Pacemaker Generates Similar Circadian Rhythms in the Fractal Structure of Heart Rate in Humans and Rats

Kun Hu1,*, Frank A.J.L. Scheer1,2, Ruud M. Buijs2,3 and Steven A. Shea1,*

1 Harvard Medical School and Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA
2 Department of Hypothalamic Integration Mechanisms, Netherlands Institute for Brain Research, Amsterdam, The Netherlands
3 Department Physiology, Instituto Biomedicas, Universidad Nacional Autónoma de México

Corresponding authors: Harvard Medical School and Division of Sleep Medicine, Brigham & Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, Phone: (617)-667-0346; fax: (617)-667-0351; email: khu{at}bidmc.harvard.edu

Harvard Medical School and Division of Sleep Medicine, Brigham & Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, Phone: (617)-732-5013; fax: (617)-278-0683; email: sshea{at}hms.harvard.edu

Aims: Adverse cardiovascular events in humans occur with a day/night pattern, presumably related to a daily pattern of behaviors or endogenous circadian rhythms in cardiovascular variables. Healthy humans possess a scale-invariant/fractal structure in heartbeat fluctuations that exhibits an endogenous circadian rhythm and changes towards the structure observed in cardiovascular disease at the circadian phase corresponding to the time of the broad peak of adverse cardiovascular events (~10 AM). To explore the relationship between the rest/activity cycle, endogenous circadian rhythmicity and cardiac vulnerability, we tested: (i) whether the fractal structure of heart rate exhibits a similar circadian rhythm in a mammalian species that is nocturnally active (Wistar rats) compared to diurnally active humans, and (ii) how this fractal structure changes after lesioning the circadian pacemaker in rats (suprachiasmatic nucleus: SCN).

Methods and results: Analysis of heart rate data collected over 10 days in 8 intact and 6 SCN-lesioned Wistar rats during constant darkness revealed that: (i) as with humans, rats exhibit an endogenous circadian rhythm in the scaling exponent characterizing the hourly fractal structure of heart rate (p = 0.0005) with larger exponents during the biological day (inactive phase for rats; active phase for humans); (ii) SCN lesioning abolished the rhythm in the fractal structure of heart rate and systematically increased the exponent (p = 0.01).

Conclusion: Rats possess a circadian rhythm of fractal structure of heart rate with a similar temporal pattern as previously observed in humans despite opposite rest/activity cycles between the two species. The SCN imparts this endogenous rhythm. Moreover, lesioning the SCN in rats results in a larger scaling exponent, as occurs with cardiovascular disease in humans.

KEYWORDS heart rate control; cardiac vulnerability; circadian rhythms; scale-invariant/fractal structure; behavior; rest/activity cycle; suprachiasmatic nucleus

Time for primary review: 29 days

* To whom correspondence may be addressed. E-mail: khu{at}bidmc.harvard.edu or sshea{at}hms.harvard.edu.

Abbreviations: DFA, detrended fluctuation analysis; SCN, suprachiasmatic nucleus; SCNx, SCN-lesioned


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