Vasodilator reserve in collateral-dependent myocardium as measured by positron emission tomography

Myocardial blood flow can be accurately quantitated in patients using positron emission tomography and oxygen-15 labelled water. The purpose of this study was to determine the vasodilator reserve in myocardium completely perfused by intramyocardial collateral blood flow. We hypothesized that altered relative flow reserve in such regions would correlate with the degree of ischaemia observed in these patients during exercise. The technique involves the inhalation of the positron emitting tracer C¹⁵O₂ which is converted to freely diffusible H₂¹⁵O by the lung. With rapid dynamic scanning, arterial and regional myocardial tissue concentrations can be obtained and time activity curves generated. With a two-compartment kinetic model, myocardial blood flow can be accurately quantitated over a wide range of blood flows. Five patients with stable exertional angina and normal ventricular function studies and who had an occluded major epicardial artery which completely opacified via intramyocardial collateral blood flow were studied. Myocardial blood flow (MBF) was measured both at rest and following an infusion of intravenous dipyridamole (0.56 mg . kg^-1) and the results were compared with measurements obtained from a group of eight normal volunteers. During resting conditions, MBF in the control group was 0.86±0.10 ml . g^-1 . min^-1 and in the patient group was 0.99±0.10 ml . g^-1 . min^-1 in normally perfused myocardium (ns) and 0.86 ± 0.14 ml . g^-1 . min^-1 in collateral-dependent myocardium (ns). Following dipyridamole, MBF increased to 3.58±0.89 ml . g^-1 . min^-1 in the control group and to 2.97±0.94 ml . g^-1 . min^-1 in the normal regions of the patients (ns). In the collateralized regions of the patients, the increase was less than that observed in the control group (1.66±1.02; P<0.005). Absolute coronary flow reserve (ACFR) (dipyridamole MBF/resting MBF) in the control group was 4.1±0.8 and in the patient group was 3.1±1.1 (ns) in normal regions and 1.9±1.0 (P<0.001) in collateralized regions. Relative coronary flow reserve, the ratio of ACFR in collateralized vs that of normally perfused myocardium was determined in each patient and correlated well with total exercise time (r=0.98;P<0.01) and peak double product (r=0.85;P=0.06) observed during a symptom-limited modified Bruce treadmill test. These studies support the hypothesis that vasodilator reserve in the distribution of non-infarcted collateral-dependent myocardium is abnormal compared with normally perfused myocardium. The degree of altered flow reserve correlates well with the degree of ischaemia during symptom-limited exercise, and may explain why these patients experience angina at high work loads.