Cardiovascular regulation in response to multiple hemorrhages: analysis and parameter estimation.

Area of Science:

• Physiology
• Biomedical Engineering
• Mathematical Biology

Background:

• Mathematical models are crucial for interpreting experimental data.
• Identifying data-informed model parameters is essential for rigorous analysis.
• Previous studies often analyze single large blood withdrawals, limiting understanding of dynamic responses.

Purpose of the Study:

• To develop a method for estimating an identifiable subset of cardiovascular model parameters from pressure and volume data.
• To analyze time-varying cardiovascular parameters during a series of blood withdrawals.
• To model cardiovascular regulation during hemorrhage using empirical functional expressions.

Main Methods:

• Parameter identifiability analysis using baseline left ventricular pressure and volume time series data.
• Estimation of time-varying parameters using piecewise linear splines to minimize data-model mismatch.
• Fitting spline trends with empirical functions to model cardiovascular regulation.
• Data collected from a Sprague-Dawley rat undergoing sequential blood withdrawals.

Main Results:

• Identifiable baseline parameters include cardiac contraction timing, systemic vascular resistance, and cardiac contractility.
• Systemic vascular resistance and cardiac contractility were identified as time-varying parameters.
• Acute decreases and partial recovery in vascular resistance and contractility were observed during each withdrawal.
• Chronic decreases in vascular resistance and contractility were noted across the series of withdrawals.

Conclusions:

• The study successfully identified and analyzed time-varying cardiovascular parameters during simulated hemorrhage.
• Findings reveal dynamic changes in systemic vascular resistance and cardiac contractility in response to blood loss.
• This approach provides a novel framework for analyzing cardiovascular responses to multiple perturbations, advancing our understanding of circulatory control.