Clinical and experimental aspects of functional and flow reserve of the myocardium

Basic research over the past 50 years has provided the clinician with important concepts for understanding human coronary physiology. One such tool is the determination of coronary blood flow reserve. Defined as the ratio of maximal to resting coronary flow, flow reserve may be helpful in assessing the need for revascularization in selected patients (1), as well as providing insight into pathophysiological states involving small arterial vessels (2-4). Many methodologies have been developed for measuring myocardial blood flow in patients, however most are limited by poor spatial resolution, the need for prolonged sampling periods or inherent inaccuracies with the measurements (5). Two invasive techniques have recently shown promise in the determination of coronary flow reserve in patients. Ultrasonic Doppler catheters have become small and steerable and can accurately assess changes in coronary blood flow velocities following infusions of vasodilators such as papaverine and adenosine. The technique has gained widespread acceptance for use in the catheterization laboratory, particularly to evaluate the success of interventions such as percutaneous trans luminal coronary angioplasty ( 6). Another invasive modality combines videodensitometry and digital subtraction angiography. This method uses a measurement of contrast density at two different vessel locations to determine the transit time and together with vascular volume can provide measurements of coronary blood flow (7). Both of these techniques are safe and show good results when validated against other accepted techniques. The major disadvantage however is that neither absolute blood flow nor transmural flow distributions can be measured. Positron emission tomography (PET) is non-invasive, and thus does not theoretically alter baseline flows such as might occur with an intracoronary catheter. Positron emitting tracers such as H20 15 are administered either intravenously or as inhaled C02 15 and are rapidly extracted by the myocardium. With the use of high resolution, rapid tomographic scanners, one can measure time activity curves in the left ventricular chamber and the myocardial regions of interest. Using tracer kinetic principles, total and regional myocardial blood flows can be accurately quantitated. The results correlate well with flow measurements obtained from radiolabeled microspheres in dogs, over a wide range of flows (8). Because of the short half-lifes of the tracers, sequential measurements can be made to evaluate multiple interventions.