# AGE-RELATED CARDIAC RESPONSE TO THEOPHYLLINE IN MAN

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1992 · $73,570

## Abstract

Human aging is associated with several significant alterations in cardiac
function that are deleterious.  The incidence of sinus node dysfunction
increases with age, and the chronotropic response to exercise is impaired
in healthy elderly persons.  Data from isolated cardiac muscle of
senescent rats reveal a prolonged duration of contraction and relaxation
when compared to younger animals.  Theophylline is a widely-used
bronchodilator drug with significant cardiac effects, including increased
heart rate and contractility.  These effects may be mediated by several
mechanisms: stimulation of the sympathetic nervous system, inhibition of
cAMP phosphodiesterase, antagonism of the binding of extracellular
adenosine at cell-surface receptors, or direct effects on the
availability of intracellular calcium.  Based on our preliminary studies
that show an increased inotropic response to intravenous theophylline in
healthy elderly men compared with healthy young men, we propose further
studies to investigate the hypothesis that the inotropic response to
acute theophylline administration is greater in elderly than in younger
adults.  We have preliminary evidence that the difference is not due to
sympathetic nervous system activation.  Therefore, autonomic blockade
should not attenuate this age-related effect.  However, chronic
theophylline administration may result in similar cardiac effects among
different age groups in the absence of sympathetic nervous system
activation, possibly due to up-regulation of adenosine receptors.  The
objectives of this study are: (1) to derive age-adjusted calculations for
systolic time intervals as a noninvasive measure of the inotropic state
of the heart; (2) to determine the age-related inotropic effect of acute
theophylline administration; (3) to determine the cardiac effects of
chronic oral theophylline administration; and (4) to determine if the
age-related differences of acute and chronic theophylline administration
on cardiac function are due to sympathetic nervous system stimulation.
The results of the proposed research will increase our understanding of
the pharmacology of the aging heart and may lead to new therapeutic
approaches for the management of cardiac disease in elderly patients.

## Key facts

- **NIH application ID:** 3121432
- **Project number:** 5R01AG009559-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** ROBERT E VESTAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $73,570
- **Award type:** 5
- **Project period:** 1991-03-01 → 1994-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121432

## Citation

> US National Institutes of Health, RePORTER application 3121432, AGE-RELATED CARDIAC RESPONSE TO THEOPHYLLINE IN MAN (5R01AG009559-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121432. Licensed CC0.

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