Administration of endotoxin in mice caused a prolonged period of depressed heart rate variability that temporally correlated with peak expression of multiple cytokines.
Does endotoxin administration reduce heart rate variability in mice, and is this effect mediated by cytokines?
Endotoxin-induced depression of heart rate variability in mice is temporally correlated with cytokine release and can be partially blunted by dexamethasone, suggesting a mechanistic role for cytokines in abnormal HRV during sepsis.
Absolute Event Rate: 694% vs 547%
p-value: p=<0.01
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.
Fairchild et al. (2009) studied Endotoxemia / Sepsis. Lipopolysaccharide (LPS) vs. Vehicle (sterile normal saline) was evaluated on Heart rate variability (HRV) and heart rate (p=<0.01). Administration of endotoxin in mice caused a prolonged period of depressed heart rate variability that temporally correlated with peak expression of multiple cytokines.