ROLE OF ADENOSINE IN HUMAN MYOCARDIAL ISCHEMIA

Project: Research project

Project Details

Description

A Metabolic Catheter has been developed which, for the first time,
allows accurate measurement of adenosine in the coronary sinus of
patients. The long-term goal of this project is to determine what role
adenosine plays in the pathogenesis of human myocardial ischemia. If
this project can demonstrate that coronary sinus adenosine concentration
is an accurate reflection of myocardial ischemia, the physiologic
assessment of obstructive coronary artery disease (CAD) visualized at
the time of cardiac catheterization will be possible. Aim 1: Develop
improved methods for the measurement of adenosine in human blood. Aim
1.1 is to develop procedures to ensure that no significant adenosine is
artifactually formed as a result of the breakdown of adenine nucleotides
released from platelets or hemolyzed red blood cells. Aim 1.2 is to
develop improved procedures to measure adenosine in blood by automated
radioimmunoassay. Aim 2: Determine if adenosine is an accurate marker
of myocardial ischemia in patients with CAD. Aim 2.1 is to determine if
coronary sinus adenosine and inosine release are a more precise
metabolic reflection of myocardial ischemia than the current gold
standard, coronary sinus lactate. Coronary sinus adenosine, inosine,
and lactate will be correlated with the ratio of myocardial blood supply
(assessed by thermodilution coronary sinus blood flow) to myocardial
demand (assessed by the rate-pressure product). Aim 2.2 is to determine
if basal and pacing-induced rises in coronary blood flow in patients
with multivessel obstructive coronary disease are in part dependent on
adenosine release. Coronary sinus adenosine and inosine levels will be
compared between patients with no epicardial or small resistance CAD to
those with multivessel CAD. Similar measurements will be repeated
during atrial pacing. Aim 2.3 is to determine if reactive hyperemia in
humans is mediated by increased production of adenosine. Patients with
obstructive CAD undergoing elective percutaneous transluminal
angioplasty will have coronary sinus adenosine and inosine levels
measured at baseline and during maximal reactive hyperemic flow. Aim
2.4 is to determine if coronary steal is due to increased interstitial
adenosine. The amount of coronary steal in CAD patients will be
determined by the severity of the initial thallium-201 defect and the
presence of delayed redistribution induced by intravenous dipyridamole
on quantitative scintigraphy, and correlated with the rise in coronary
sinus adenosine and inosine. Aim 3: Determine if adenosine is the link
between myocardial ischemia and angina. Aim 3.1 is to determine if
patients with predominantly "silent ischemia" have no change or less of
rise in coronary sinus adenosine and inosine in response to stress than
patients with symptomatic CAD. Aim 3.2 is to determine if ischemia in
"Syndrome X" is associated with a rise in coronary sinus adenosine and
inosine, which would strengthen the notion that adenosine production in
this condition dilates epicardial coronary arterioles, producing
subendocardial-to-epicardial steal.
StatusFinished
Effective start/end date7/1/926/30/96

Funding

  • National Institutes of Health: $107,456.00
  • National Institutes of Health
  • National Institutes of Health: $90,598.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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