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.
