Title | Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. | ||
Author | Fairchild, Karen D; Saucerman, Jeffrey J; Raynor, Laura L; Sivak, Joseph A; Xiao, Yuping; Lake, Douglas E; Moorman, J Randall | ||
Journal | Am J Physiol Regul Integr Comp Physiol | Publication Year/Month | 2009-Oct |
PMID | 19657103 | PMCID | PMC2763816 |
Affiliation | 1.Departments of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. Kdf2n@virginia.edu. |
Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS (Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNFalpha 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3-9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low- and high-frequency HRV. Administration of recombinant TNFalpha caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.