Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial

Area of Science:

• Physiology
• Cardiovascular Research
• Sepsis Pathogenesis

Background:

• Heart rate variability (HRV) reflects autonomic nervous system function.
• Endotoxemia, a state of elevated endotoxin levels, can impact physiological systems.
• Understanding HRV changes during endotoxemia is crucial for sepsis research.

Purpose of the Study:

• To investigate the association between human endotoxemia and the loss of physiological beat-to-beat heart rate variability.
• To assess the impact of endotoxin on heart rate regularity using various analytical measures.

Main Methods:

• Prospective, randomized, crossover, single-blind study involving healthy volunteers.
• Intravenous administration of Escherichia coli endotoxin or saline placebo.
• Continuous electrocardiogram recording and analysis of R-R intervals using time domain, frequency domain, and approximate entropy.

Main Results:

• Endotoxin administration led to a significant loss of heart rate variability across all measured domains.
• Heart rate regularity, measured by approximate entropy, increased following endotoxin infusion.
• These changes persisted even when ibuprofen administration blocked fever and other endotoxin-related symptoms.

Conclusions:

• Human endotoxemia causes a measurable loss of heart rate variability and increased regularity.
• Approximate entropy changes may serve as an early indicator for sepsis detection.
• Reduced heart rate regularity aligns with models of multiple organ system dysfunction syndrome involving physiological uncoupling.