# Disentangling the Mechanisms of Coronary Blood Flow Regulation through Multi-scale Modeling

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $668,090

## Abstract

Disentangling the Mechanisms of Coronary Blood Flow Regulation through Multi-scale Modeling
The coronary circulation is regulated by numerous mechanisms that precisely modulate myocardial perfusion
to ensure that myocardial oxygen delivery (supply) is adequate to meet the metabolic requirements for ATP
production (demand). This balance between coronary blood flow and myocardial oxygen consumption (MVO2)
is preserved over a variety of patho-physiologic perturbations, including critical reductions in perfusion
pressure which occur distal to sites of atherosclerotic stenosis. The innate ability of the coronary circulation to
maintain blood flow constant as driving pressures are reduced to values as low as 40-60 mmHg is an essential
phenomenon that mitigates hypoperfusion, cardiac dysfunction, and overt ischemic injury. Despite the crucial
nature of this intrinsic response, understanding the mechanisms responsible for coronary pressure-flow
autoregulation remains one of the most fundamental questions in the coronary field today.
The most prominent theories to explain coronary autoregulatory behavior are the local metabolic and myogenic
hypotheses. However, given that these pathways share common end-effector pathways and microvascular
responses, differ transmurally across layers of the myocardium, and are influenced by structural and contractile
properties of the myocardium, our knowledge remains rather phenomenological. The primary goal of this
proposal is to address this deficit through computational and experimental studies to build, test, and refine
competing hypotheses for the metabolic mechanism in the context of a multi-scale model of coronary flow
regulation. Our approach builds on our recent efforts with constrained mixture theory models and in vivo
assessment of coronary pressure at zero-flow (Pzf), an index of underlying myogenic tone. Applying this
experimental and modeling framework to test and refine hypotheses regarding pathologically over-active
myogenic response in coronary microvascular dysfunction associated with obesity will provide further insight
into short- vs. long-term impact of microvascular adaptions in health and disease.

## Key facts

- **NIH application ID:** 10465986
- **Project number:** 1R01HL158723-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** DANIEL A BEARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $668,090
- **Award type:** 1
- **Project period:** 2022-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465986

## Citation

> US National Institutes of Health, RePORTER application 10465986, Disentangling the Mechanisms of Coronary Blood Flow Regulation through Multi-scale Modeling (1R01HL158723-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465986. Licensed CC0.

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