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Initial Infarct Size Predicts Subsequent Cardiac Remodeling in the Rat Infarct Model: An In Vivo Serial Pinhole Gated SPECT Study

¹ UHP-INSERM U684, Faculty of Medicine, Nancy, France; ² Nuclear Medicine Department, University Hospital, Nancy, France; ³ In Vivo Cellular and Molecular Imaging Center, University of Brussels (VUB), Brussels, Belgium; ⁴ Laboratory of Surgery School, Nancy, France; and ⁵ Superior National School of Chemical Industries, CNRS and INPL, Nancy, France

Correspondence: For correspondence contact: Fatiha Maskali, MSc. Unité mixte INSERM-UHP U684, Faculté de Médecine de Nancy, 54505 Vandoeuvre-Les-Nancy, France. E-mail: fatiha.maskali{at}medecine.uhp-nancy.fr

The rat infarct model is widely used to study left ventricular (LV) remodeling, a main cause of heart failure characterized by progressive LV dilatation. Using pinhole collimators and advances in data processing, gated SPECT was recently adapted to image the rat heart. The aim of this study was to assess this new imaging technique for predicting and quantifying variable LV remodeling from the rat infarct model. Methods: Pinhole ^99mTc-sestamibi gated SPECT was validated for determining LV volume and identifying the necrotic and nonviable LV segments (<50% of ^99mTc-sestamibi uptake) in rats, and it was applied to monitor rat LV function from 48 h to 12 wk after occlusion of the left anterior descending coronary artery (LAD) (n = 20) or sham operation (n = 9). Results: In LAD-occluded rats, 48-h SPECT necrosis was large (30% LV) in 6, limited (<30% LV) in 6, and undetectable in 8. End-diastolic volume of LAD-occluded rats was equivalent to that of sham-operated rats at 48 h (320 ± 84 µL vs. 293 ± 48 µL; not significant) but became higher at 12 wk (501 ± 191 µL vs. 343 ± 46 µL; P = 0.01). The follow-up increase in end-diastolic volume, which reflects the remodeling process, was closely related to the initial extent of necrosis revealed by the SPECT images (P < 0.001; R² = 0.85). This increase was limited in sham-operated rats (50 ± 15 µL) and in the LAD-occluded rats with undetectable necrosis (55 ± 35 µL) but it was around 3- and 7-fold higher in the LAD-occluded rats with limited (165 ± 57 µL) and large (366 ± 113 µL) necrosis, respectively. Conclusion: The variable LV remodeling documented after coronary occlusion in rats closely relates to the variable extent of necrosis provided by this model. Pinhole gated SPECT allows this remodeling to be predicted and quantified and, hence, constitutes an original tool for the experiments scheduled on the rat infarct model.

Key Words: remodeling • myocardial infarction • rat • gated SPECT • sestamibi

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