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PURPOSE: The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). METHODS: A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using (99m)Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. RESULTS: Estimated MPR was higher in control subjects than in patients (3.36 +/- 0.66 vs 1.91 +/- 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 +/- 0.78 vs 1.93 +/- 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 +/- 0.71 vs 1.83 +/- 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). CONCLUSION: LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.