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Endotoxin depresses heart rate variability in mice: cytokine and steroid effects.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2009 Oct; Vol. 297 (4), pp. R1019-27. Date of Electronic Publication: 2009 Aug 05. - Publication Year :
- 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 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.
- Subjects :
- Animals
Blood Pressure
Body Temperature
Cytokines administration & dosage
Disease Models, Animal
Electrocardiography, Ambulatory
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
Sepsis chemically induced
Sepsis drug therapy
Sepsis immunology
Sepsis prevention & control
Telemetry
Time Factors
Tumor Necrosis Factor-alpha blood
Up-Regulation
Cytokines blood
Dexamethasone pharmacology
Glucocorticoids pharmacology
Heart Rate drug effects
Sepsis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 297
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19657103
- Full Text :
- https://doi.org/10.1152/ajpregu.00132.2009