Endotoxin Depresses Heart Rate Variability In Mice

[Lokzo]

Depression of HRV is associated with adverse outcomes in a number of chronic and acute pathological states, including myocardial infarction (17), congestive heart failure (3), diabetes (19), fetal asphyxia (18), and sepsis (6). In all of these conditions, the assumption has been that there is abnormal signaling from or response to the autonomic nervous system, though mechanistic studies are few. In addition, limited clinical studies suggest an association between a systemic inflammatory response and decreased HRV (15). In the case of chronic illness, an inverse correlation has been reported between plasma TNFα levels and HRV in adults with congestive heart failure (20) and between plasma IL-6 levels and HRV in adults with diabetes (9). In acute illness, elevated plasma IL-6 has also been linked to depressed HRV in adults with sepsis (32). In experimental sepsis in both animal models and healthy human volunteers, administration of lipopolysaccharide (LPS, endotoxin from gram-negative bacteria) decreases HRV (2, 7, 8, 21). While these data point to an association between the systemic inflammatory response and changes in HRV, causal links between the two have not been established.

Our group has previously shown that abnormal HR characteristics (HRC) comprising depressed HRV and repetitive brief HR decelerations often precede clinical signs of sepsis by as much as 24 h in neonatal intensive care unit patients (12, 15–17, 19, 20, 26). Other conditions and interventions have also been associated with abnormal HRC in neonatal intensive care unit patients without sepsis. Further characterization of abnormal HRC during sepsis would add to the diagnostic utility of HRC monitoring, and, to this end, we developed a mouse model of continuous radiotelemetric monitoring of ECG during exposure to bacterial toxins. We show that LPS leads to increased levels of multiple cytokines and to depression of HRV in both parasympathetic and sympathetic frequency bands, suggesting a balanced effect on the autonomic nervous system (ANS), or a non-ANS mechanism. TNFα administration was sufficient to induce similar changes, while cytokine-suppressing glucocorticoids reduced the duration of LPS-induced HRV depression and, interestingly, profoundly increased HRV when given alone. The changes in HRV were not obviously due to systemic effects of LPS or cytokines, such as hypotension or hypothermia. We propose that cytokines play a mechanistic role in reduced HRV during sepsis.


Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

 

[Grapelander]

Heart Rate Variability: An Indicator of Self-Regulatory Capacity, Autonomic Function and Health​

HeartMath Institute: An optimal level of HRV within an organism reflects healthy function and an inherent self-regulatory capacity, adaptability, and resilience. While too much instability, such as arrhythmias or nervous system chaos, is detrimental to efficient physiological functioning and energy utilization, too little variation indicates age-related system depletion, chronic stress, pathology or inadequate functioning in various levels of self-regulatory control systems.

The importance of HRV as an index of the functional status of physiological control systems was noted as far back as 1965, when it was found that fetal distress was preceded by reductions in HRV before any changes occurred in heart rate. In the 1970s, reduced HRV was shown to predict autonomic neuropathy in diabetic patients before the onset of symptoms. Reduced HRV also was found to be a higher risk factor of death post-myocardial infarction than other known risk factors. It has been shown that HRV declines with age and that age-adjusted values should be used in the context of risk prediction. Age-adjusted HRV that is low has been confirmed as a strong, independent predictor of future health problems in both healthy people and in patients with known coronary artery disease and correlates with all-cause mortality.

Reduced HRV may correlate with disease and mortality because it reflects reduced regulatory capacity and ability to adapt/ respond to physiological challenges.

Heart rate variability also indicates psychological resiliency and behavioral flexibility, reflecting an individual’s capacity to self-regulate and effectively adapt to changing social or environmental demands.