Computational model-based assessment of baroreflex function from response to Valsalva maneuver

Abstract

Functional metrics of autonomic control of heart rate, including baroreflex sensitivity, have been shown to be strongly associated with cardiovascular risk. A decrease in baroreflex sensitivity with aging is hypothesized to represent a contributing causal factor in the etiology of primary hypertension. To assess baroreflex function in human subjects, two complementary methods to simulate the response in heart rate elicited by the Valsalva maneuver were developed and applied to data obtained from a cohort of healthy normal volunteers. The first method is based on representing the baroreflex arc as a simple linear filter, transforming changes in arterial pressure to changes in R-R interval. The second method invokes a physiologically based model for arterial mechanics, afferent baroreceptor strain-dependent firing, and control of heart rate via central autonomic response to changes in afferent inputs from aortic and carotid sensors. Analysis based on the linear filter model reveals that the effective response time of the baroreflex arc tends to increase with age in healthy subjects and that the response time/response rate is a predictor of resting systolic pressure. Similar trends were obtained based on the physiologically based model. Analysis of the Valsalva response using the physiologically based model further reveals that different afferent inputs from the carotid sinus and the aortic arch baroreceptors govern different parts of the heart rate response. The observed relationship between baroreflex sensitivity and systolic pressure is surprising because hypertensive subjects were excluded from the study, and there was no observed relationship between arterial pressure and age. NEW & NOTEWORTHY We introduce two methods to assess baroreflex function from data recorded from human subjects performing the Valsalva maneuver. Results demonstrate that the baroreflex response time tends to increase with age in healthy subjects, that response time represents a predictor of resting systolic pressure, and that the Valsalva response reveals different effects mediated by baroreceptors in the carotid sinus compared with those in the aortic arch.

Multiscale Modeling of Cardiovascular Function Predicts That the End-Systolic Pressure Volume Relationship Can Be Targeted via Multiple Therapeutic Strategies

“…A real heart would obviously be subject to autonomic control. Although beyond the scope of this work, it will be possible to reproduce autonomic control in future research by implementing a virtual baroreceptor ( Kosinski et al, 2018 ). This could be done by monitoring the arterial blood pressure predicted by the model and adjusting the heart-rate in order to maintain pressure within pre-set limits.…”

A model-based analysis of autonomic nervous function in response to the Valsalva maneuver

“…Several deterministic mathematical models have been proposed to explain the autonomic response to the VM. These can be split into the following two categories: 1) closed-loop models simulating blood pressure and heart rate dynamics simultaneously (30,37,40,59) and 2) open-loop models that either take blood pressure as an input and compute heart rate as an output or take heart rate as an input and compute blood pressure as an output (10,35). In this study, we pursue the open-loop approach, predicting changes in heart rate in response to the VM.…”

Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats

“…Numerous techniques exist for assessing baroreflex function based on measuring responses to externally imposed changes in pressure. For example, the Valsalva maneuver elicits a drop in transmural pressures in the aortic arch and carotid arteries, generating a reflex-mediated increase in HR, which may be analyzed by a variety of mathematical techniques (39). Studies in animals and humans have also used administration of vasodilators and vasoconstrictors to bring about arterial pressure and corresponding HR changes to assess the baroreflex response (40,41).…”

“…Data on RR interval — RR( t ), HR =1/RR — were compared with predictions from a linear filter similar to the model used by Kosinski et al ( 39 ) analyzing the autonomic response to the Valsalva maneuver in human subjects. Using the MAP data as an input, the model assumes that the RR interval determined by the autonomic baroreflex is captured by the first-order linear filter:…”

“…Time-series analysis of the telemetry data is based on the assumption that when the HR is controlled through the baroreflex, changes in arterial pressure should effect changes in HR; i.e., transient increases/ decreases in MAP and/or PP should be followed by proportional decreases/increases in HR. The simple linear filter-based approach of Kosinski et al (39) was modified to distinguish time windows when the baroreflex is functioning ("on") or is not functioning ("off "). In other words, "off " represents times when the expected relationship between BP and HR does not exist.…”