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Myocardial perfusion imaging with adenosine triphosphate (ATP) has been used increasingly to diagnose coronary artery disease (CAD) and assess risk for this disease. This study compared absolute myocardial blood flow (MBF) and myocardial flow reserve index (MFR) with ATP and dipyridamole (DIP) in patients with CAD. MBF was quantified by 15O-H2O PET in 21 patients with CAD (17 male, 4 female), aged 55 to 81 years. MBF was measured at rest, during intravenous injection of ATP (0.16 mg/kg/min), and again after DIP infusion (0.56 mg/kg). Regions of interest were drawn in nonischemic and ischemic segments based on findings from thallium-201 (201T1) scintigraphy and coronary angiography (CAG). Absolute MBF values and indexes of MFR were calculated in nonischemic and ischemic segments. Intravenous injection of ATP and DIP significantly increased MBF in nonischemic (2.4 +/- 0.9 and 2.1 +/- 0.8 ml/g/min, respectively; p < 0.01, for both) and in ischemic segments (1.3 +/- 0.4 and 1.5 +/- 0.4 ml/g/min, respectively; p < 0.01, for both). There was a significant difference in MBF values between ATP and DIP in nonischemic segments (p < 0.05), which was not observed in ischemic segments. In nonischemic segments, ATP produced higher MFR than DIP (2.1 +/- 0.8 and 1.8 +/- 0.7, respectively; p < 0.05), while no significant difference was observed in ischemic segments (1.5 +/- 0.6 and 1.7 +/- 0.3, respectively). ATP produced a greater hyperemia than DIP between the ischemic and nonischemic myocardium in patients with CAD. ATP is as effective as DIP for the diagnosis of CAD.

Purpose: The purpose of this study was to evaluate the effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor (Cilazapril) for early hypertensive patients in terms of coronary blood flow reserve evaluated by 13NH3-positron emission tomography (PET)., Methods: Before and after 12 weeks of ACE inhibitor treatment, 13NH3-PET with dipyridamole provocation test was performed, and definite myocardial perfusion and coronary flow reserve (CFR) were calculated., Results: Compared to our normal subjects previously reported (2.61+/-0.74), average coronary flow reserve was decreased (1.70+/-0.64 in hypertensive patients), and improved after treatment (1.77+/-0.52), but not significantly. Of 12 patients, five (42%) showed improved coronary flow reserve from 1.34 to 1.99 without a significant change in the resting flow. Only one patient (8%) showed deterioration after the ACE inhibitor treatment. The coronary vascular resistance (CVR) after ACE inhibitor treatment of the patients with CFR < 2.0 decreased significantly compared with those with CFR> or = 2.0 (p < 0.03)., Conclusions: These results indicate that hypertensive patients at the early stage show decreased coronary flow reserve despite having normal resting flow. Treatment with an ACE inhibitor (Cilazapril) for 12 weeks improved coronary flow reserve in 42% of our patients. The CVR of the patients with CFR < 2.0 showed improvement compared to those with CFR> or = 2.0. This result indicates that an ACE inhibitor (e.g., Cilazapril) should be one of the choices for improving CFR if hypertensive patients in early stage show signs of ischemia or diastolic dysfunction, which may be one of the sequels of reserve restriction.

A variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.

Unlabelled: Noninvasive quantification of regional myocardial blood flow (MBF) has been successfully achieved with N-13 ammonia. The microsphere method as a simple method for quantifying regional myocardial blood flow was reevaluated in comparison with Patlak graphical analysis. In addition coronary vasodilator reserve (CVR) was estimated by both methods., Methods: Dynamic N-13 ammonia PET studies were performed in 10 healthy volunteers and 10 patients with coronary artery disease at baseline and after dipyridamole infusion (0.56 mg/kg). MBF was estimated by the microsphere method at various times and by Patlak graphical analysis. In order to reduce the noise level in the microsphere method, MBF estimates were also performed after data in 10-40 seconds were averaged., Results: In the studies on normal subjects MBF (ml/min/g) determined by the microsphere method significantly differs from time to time. However, MBF determined by the modified microsphere method [with average (Extraction fraction) x MBF values obtained between 100 and 120 sec] linearly correlated well with MBF by Patlak graphical analysis (r = 0.97, slope = 0.98, intercept = 0.20). In the studies on patients with coronary artery disease a good agreement of the MBF estimates was also observed (r = 0.97, slope = 0.98, intercept = 0.22). In the studies on the normal subjects and patients with coronary artery disease, CVR obtained by the modified microsphere method after correcting the overestimated MBF values also correlated well with that by Patlak graphical analysis (r = 0.90, slope = 1.14, intercept = -0.15, and r = 0.92, slope = 0.82, intercept = 0.25, respectively)., Conclusion: The modified microsphere method is a very simple and reliable approach for quantifying MBF with N-13 ammonia PET which is comparable to Patlak graphical analysis. It also makes possible CVR assessment as accurate as Patlak graphical analysis.

To assess the clinical value of combined SPECT imaging with I-123-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and thallium-201 (Tl), the findings were compared with those obtained in a stress Tl study and positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in 22 patients with myocardial infarction. In 20 patients who underwent a stress Tl study, among 75 hypoperfused segments, 27 segments exhibited less BMIPP uptake than Tl (discordant segments), and the remaining 48 segments showed a similar decrease in BMIPP uptake (concordant segments). Twenty-two of 27 discordant segments (81%) exhibited redistribution on stress Tl study. On the other hand, only one of the 48 concordant segments had redistribution (p < 0.001). In 10 patients who underwent a FDG PET study, among 33 hypoperfused segments, seven segments were discordant segments, and the remaining 25 segments were concordant segments. Seven of the eight discordant segments (88%) demonstrated an increase in FDG uptake. In contrast, only five of 25 concordant segments (20%) showed increase in FDG uptake (p < 0.01). Thus, the segments showing discordant BMIPP uptake are considered to be ischemic but viable myocardium. We conclude that combined imaging with BMIPP and Tl is a useful mean for evaluating tissue viability in patients with coronary artery disease, but it may underestimate the extent of tissue viability, compared with FDG PET imaging.

Experimental studies indicated the clearance rate constant of 11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n = 7), after oral glucose administration (n = 4), and during dobutamine infusion (n = 7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008 min-1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.