# Myocardial infarction and mechanisms of impaired sleep and breathing

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $391,250

## Abstract

SUMMARY
Impaired sleep and breathing has multiple systemic and organ-specific effects including inflammation,
sympathetic activation and heightened metabolic and cardiovascular risk. Recently, attention has focused on
the relationship between cardiac events and disrupted sleep and breathing; sleep disordered breathing is
associated with poor cardiac outcomes, and cardiac disease has, in turn, been identified as a possible cause
of sleep disordered breathing and fragmentation of sleep. We propose that poor sleep quality may affect
primary outcomes after myocardial infarction (MI), and contribute to a feedforward mechanism leading to
subsequent cardiac events and worse outcomes. We have developed murine models to examine the
relationship between experimentally-induced MI and impaired sleep and breathing in both the presence and
absence of obesity, a major co-morbidity in cardiovascular disease. Our preliminary studies demonstrate that
two days of sleep fragmentation in healthy lean mice induces a pro-inflammatory state in the heart and
significantly increases cardiac dysfunction and mortality to subsequent MI. Conversely, in mice with MI there
are marked sleep disturbances, primarily characterized by (1) a striking increase in total NREM sleep time in
the dark/active period, simulating `daytime sleepiness' in humans and (2) a marked increase in arousal
frequency, predominantly in the light period of consolidated sleep, simulating fractured, poor sleep quality in
humans. Associated with these changes in sleep after MI, we observed an increase in cytokine expression in
the hypothalamus that was dependent on intact cardiac sympathetic pathways. We, will use state-of-the-art
physiologic techniques to investigate the relationship between sleep disruption and MI and mechanistically
examine the role of cardiac neural and pro-inflammatory pathways in lean and obese mice. Aim 1 will examine
the effect of prior sleep disruption on worsening MI outcomes and Aims 2-4 will examine the effect of MI on
subsequent sleep and breathing disruption and the development of a feedforward mechanism further
worsening MI outcomes. Our aims are:
Aim 1: To determine the impact of prior sleep fragmentation and the role of cardiac sympathetic pathways and
obesity on cardiac function and mortality after MI. Aim 2: To determine the role of MI-mediated breathing
instability on the development of sleep fragmentation and `daytime sleepiness.' Aim 3: To determine the role
of cardiac afferent sympathetic pathways in fragmenting sleep and increasing `daytime sleepiness' after MI.
Aim 4: To determine the role of activation of CNS cytokines in increasing `daytime sleepiness' after MI.
This study will provide insights into the relationship between dysfunctional sleep and breathing and cardiac
pathology using discrete interventions to define mechanistic pathways that are not possible in clinical studies.
Moreover, our long-term goal is to translate our findings back to the clinical arena a...

## Key facts

- **NIH application ID:** 9902504
- **Project number:** 5R01HL132877-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** CHRISTOPHER P O'DONNELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902504

## Citation

> US National Institutes of Health, RePORTER application 9902504, Myocardial infarction and mechanisms of impaired sleep and breathing (5R01HL132877-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9902504. Licensed CC0.

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