Abstract 567: Myocardial Perfusion Heterogeneity Correlates With Capillary Density in a Rat Model of Diabetic Cardiomyopathy
Introduction: An early hallmark of coronary artery disease (CAD) is endothelial dysfunction and microcirculation abnormalities. Such alterations are also observed in the setting of diabetic cardiomyopathy. The noninvasive assessment of microcirculation abnormalities would therefore be of great experimental value for the study of cardiac alterations induced by early CAD or diabetes.
Hypothesis: We hypothesized that the experimental quantification of myocardial perfusion heterogeneity using small animal SPECT imaging would allow for the detection of microcirculation abnormalities.
Methods: Twelve Sprague-Dawley rats received an intraperitoneal injection of either streptozotocin (STZ, 65 mg/kg, n = 6) for the induction of type 1 diabetes, or vehicle (control, n = 6). Five weeks later, myocardial perfusion was assessed following IV injection of the perfusion tracer Tl-201 (118±6 MBq) using in vivo pinhole SPECT imaging (resolution 0.9 mm; total # of acquired myocardial events, 8 – 13×106). Following euthanasia, the hearts were quickly excised, rinsed, and weighed. Immunohistochemistry of the endothelial marker CD31 quantified capillary density. A Markovian analysis of myocardial perfusion heterogeneity was performed on Tl-201 images. Markovian heterogeneity analysis examines the probability that a pixel with a given intensity will have a neighbor with a different intensity, leading to the determination of the heterogeneity index (HI).
Results: Significant differences were observed between control and STZ animals with respect to body weight (435±16 vs. 187±10 g, respectively, p<0.01), heart weight (1.2±0.1 vs. 0.7±0.1 g, respectively, p<0.01), heart-to-body weight ratio (2.9±0.1 vs. 4.0±0.3 mg/g, respectively, p<0.05), and blood glucose (62±10 vs. 332±12 mg/dL, respectively, p<0.01). An excellent correlation was observed between capillary density and myocardial perfusion heterogeneity as quantified using HI (R2 = 0.8, P< 0.05).
Conclusions: Myocardial perfusion heterogeneity as quantified using Markovian analysis of small animal SPECT perfusion images correlates with capillary density and supports this noninvasive marker of microcirculation abnormalities in an experimental animal model of diabetic cardiomyopathy.