Endotoxin depresses heart rate variability in mice: cytokine and steroid effects
- 1 October 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 297 (4), R1019-R1027
- https://doi.org/10.1152/ajpregu.00132.2009
Abstract
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 TNFα 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 TNFα 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.Keywords
This publication has 33 references indexed in Scilit:
- A combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetesScandinavian Journal of Clinical and Laboratory Investigation, 2008
- Low-dose steroid altersin vivoendotoxin-induced systemic inflammation but does not influence autonomic dysfunctionInnate Immunity, 2007
- DEPRESSED HEART RATE VARIABILITY IS ASSOCIATED WITH HIGH IL-6 BLOOD LEVEL AND DECLINE IN THE BLOOD PRESSURE IN SEPTIC PATIENTSShock, 2007
- Heart rate dynamics in iNOS knockout miceLife Sciences, 2006
- Heart Rate Characteristics Monitoring for Neonatal SepsisIEEE Transactions on Biomedical Engineering, 2005
- Relations of inflammatory markers to lipid levels and autonomic tone in patients with moderate and severe chronic kidney disease and in patients under maintenance hemodialysisClinical Nephrology, 2005
- Heart Rate Characteristics: Novel Physiomarkers to Predict Neonatal Infection and DeathPEDIATRICS, 2005
- Approximate entropy of fetal heart rate variability as a predictor of fetal distress in women at term pregnancyActa Obstetricia et Gynecologica Scandinavica, 2005
- Experimental human endotoxemia increases cardiac regularityCritical Care Medicine, 1996
- Spectral analysis of heart rate variability in the sepsis syndromeClinical Autonomic Research, 1993