Wearable Patch Heart Rate Variability is An Early Marker of Systemic Inflammation During Experimental Human Endotoxemia

Heart rate variability (HRV), the quantification of beat-to-beat variability, has been studied as a potential prognostic marker in inflammatory diseases such as sepsis. HRV normally reflects significant levels of variability in homeostasis, which can be lost under stress. Much effort has been placed in interpreting HRV from the perspective of quantitatively understanding how stressors alter HRV dynamics, but the molecular and cellular mechanisms that give rise to both homeostatic HRV and changes in HRV have received less focus. Here, we develop a mathematical model of human endotoxemia that incorporates the oscillatory signals giving rise to HRV and their signal transduction to the heart. Connections between processes at the cellular, molecular, and neural levels are quantitatively linked to HRV. Rhythmic signals representing autonomic oscillations and circadian rhythms converge to modulate the pattern of heartbeats, and the effects of these oscillators are diminished in the acute endotoxemia response. Based on the semimechanistic model developed herein, homeostatic and acute stress responses of HRV are studied in terms of these oscillatory signals. Understanding the loss of HRV in endotoxemia serves as a step toward understanding changes in HRV observed clinically through translational applications of systems biology based on the relationship between biological processes and clinical outcomes.

Download Full-text

Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes

Acta Endocrinologica ◽

10.1530/eje-07-0090 ◽

2007 ◽

Vol 157 (1) ◽

pp. 31-38 ◽

Cited By ~ 38

Author(s):

J-M González-Clemente ◽

C Vilardell ◽

M Broch ◽

A Megia ◽

A Caixàs ◽

...

Keyword(s):

Insulin Resistance ◽

Heart Rate ◽

Heart Rate Variability ◽

Type 1 Diabetes ◽

Systemic Inflammation ◽

Insulin Dose ◽

Plasma Concentrations ◽

Glucose Disposal ◽

Low Grade

Objective: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. Design: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. Methods: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor α receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. Results: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (r=−0.244, P=0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; r=−0.231, P=0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. Conclusions: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.

Download Full-text