Sensitivity analysis of closed-loop one-chamber and four-chamber models with baroreflex

Area of Science:

• Cardiovascular physiology
• Computational modeling
• Systems biology

Background:

• The baroreflex is a critical cardiovascular control mechanism.
• In silico models are valuable for studying complex physiological systems.
• Understanding parameter influence is key for accurate physiological modeling.

Purpose of the Study:

• To conduct the first global sensitivity analysis of closed-loop baroreflex models.
• To compare regulated and unregulated cardiovascular models.
• To identify key parameters influencing cardiovascular metrics in baroreflex regulation.

Main Methods:

• Utilized closed-loop in silico models of baroreflex regulation.
• Coupled baroreflex models to pulsatile mechanical heart models (1-chamber and 4-chamber).
• Performed global sensitivity analysis on cardiovascular and baroreflex parameters.

Main Results:

• Regulated parameters showed reduced influence compared to unregulated models.
• Parasympathetic arc parameters were most sensitive in physiological resting states.
• Model outputs like pressure and heart rate are significantly affected by specific regulatory pathways.

Conclusions:

• Baroreflex regulation modulates parameter influence on cardiovascular outputs.
• Parasympathetic pathways are critical drivers of cardiovascular dynamics in these models.
• This research is a foundational step towards using regulatory models in personalized healthcare.