Abstract
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Objectives: To dynamically evaluate the effect of metformin (MF) in a rat model of ischemia/reperfusion (I/R) injury at different time points by 18F-fluorodeoxyglucose (18F-FDG) micro PET/CT imaging.
Methods: The I/R injury model in Sprague-Dawley (SD) rat was established by ligation of left anterior descending (LAD) coronary artery near the pulmonary arch root for 30min. SD rats (n=12) were randomly divided into 2 groups: control group (n=6) without any intervention and metformin intervention (MF) group (n=6) with oral administration of metformin (50 mg/kg) twice per day. Rats were anesthetized with isoflurane. Gated 18F-FDG(40Mbq)micro PET/CT imaging was performed at different time points (day 1st , day 7th , day 14th and day 30th after surgery) for 10min. Volumes of interest (VOIs) were drawn to identify different myocardium regions (ischemia center, peri-ischemia area and remote area). Standardized uptake values (SUVs) (SUVmean and SUVmax) were analyzed to evaluate the FDG uptake activity, and center/remote ratio was calculated. In addition, the left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and LV ejection fraction (LVEF) were obtained. 30th day at the end of study, the rats were scarified and myocardial ischemia was analyzed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining and demonstrated by pathology.
Results: In control group, center/remote ratio was gradually reduced from 1st day to 30th day after reperfusion. In the meantime, LVEDV was increased gradually with time. And there was a significant negative correlation between center/remote ratio and LVEDV (r = -0.732,p<0.05). In MF group, center/remote ratio was relatively stable(p>0.05). At day 30th after reperfusion, center/remote ratio in MF group was significantly higher than that in control group (0.81±0.06 vs 0.65±0.09, p<0.05) while LVEDV in MF group was significantly lower than in control group (358.21±22.62 vs. 457.53±29.91, p<0.05). It indicated that MF attenuated the severity of I/R injury on the myocardium, thus, delayed the development of LV remodeling. However, no significant difference of LVEF was observed between control group and MF group at different time points after reperfusion(p>0.05).
Conclusions: MF attenuated the severity of I/R injury on myocardium and thus, may delay or prevent the progress of LV remodeling. It warrants further investigation to evaluate the effects of I/R injury on the myocardium with different dose of MF treatment. Keywords: ischemia/reperfusion injury; metformin; PET/CT; 18F-FDGFund project: National Natural Science Fund (NO.81071177, 81571717)