Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although ¹⁸F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with ¹⁸F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. ¹⁸F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = −0.669, P = 0.010). PET imaging identified significantly higher left ventricular ¹⁸F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The ¹⁸F-FDG signal correlated with ejection fraction (r = −0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using ¹⁸F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.

炎症有助于心肌缺血后的心室重构，但人们对炎症在非缺血性心力衰竭中的作用了解甚少。致病过程中难以连续评估局部组织炎症。尽管¹⁸ F-FDG会积聚在炎症性白细胞中，因此可以识别心肌微环境中的炎症，但尚不清楚这种成像技术是否可以隔离压力超负荷心力衰竭中的弥散性白细胞。我们旨在评估在压力超负荷引起的心力衰竭的早期阶段是否可以连续成像¹⁸ F-FDG的炎症，并将时间过程与心脏MRI评估的功能障碍进行比较。方法：对C57Bl6 / N小鼠行主动脉缩窄（TAC）（n = 22），假手术（n = 12）或冠状动脉结扎作为炎症阳性对照（n = 5）。TAC后2天和8天，MRI评估了心室的几何形状和收缩功能。免疫染色确定了压力超负荷早期炎症性白细胞浸润的程度。在TAC后第3和第7天进行了^18次F-FDG PET扫描，在氯胺酮-甲苯噻嗪麻醉下抑制心肌葡萄糖的摄取。结果：与假手术相比，压力超负荷引起左心室快速扩张（收缩末期容积：第2天：40.6±10.2μLvs. 23.8±1.7μL，P <0.001）。收缩功能也同样受损（第2天的射血分数：40.9％±9.7％对59.2％±4.4％，P<0.001）。收缩损伤的严重程度与第8天的组织学定义的心肌巨噬细胞密度成比例（r = -0.669，P = 0.010）。PET成像发现，第3天，TAC小鼠的左心室¹⁸ F-FDG积聚明显高于假小鼠（注射剂量[％ID] / g为10.5±4.1％，而3.8±0.9％ID / g，P <0.001），并且在第7天（7.8±3.7％ID / g与3.0±0.8％ID / g，P = 0.006），尽管在TAC小鼠中心肌细胞抑制的效率是可变的。的¹⁸ F-FDG的信号与射血分数（相关- [R = -0.75，P = 0.01）和心室容积（[R = 0.75，P <0.01）。Western免疫印迹法显示TAC后8 d，左心室心肌葡萄糖转运蛋白4表达增加60％，表明葡萄糖代谢发生改变。结论： TAC引起左心室几何结构和收缩功能的快速改变，同时炎症性巨噬细胞同时适度浸润。使用¹⁸ F-FDG PET成像，新陈代谢的重塑掩盖了炎性白细胞信号。要确定压力超负荷中的弥漫性局部炎症，必须使用更具选择性的炎症示踪剂。