BACKGROUND The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with 99mTc-RP805 and dynamic 201Tl for determination of myocardial blood flow, to quantify the effects of intracoronary delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. METHODS Studies were performed in control pigs (n=5) and pigs following 90-minute balloon occlusion-induced ischemia/reperfusion (I/R) of left anterior descending artery (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual isotope imaging was performed with 99mTc-RP805 and 201Tl along with contrast cineCT to assess left ventricular function. RESULTS The ischemic to nonischemic ratio of 99mTc-RP805 was significantly increased following I/R in saline group (4.03±1.40), and this ratio was significantly reduced with rTIMP-3 treatment (2.22±0.57; P=0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment group was associated with an improvement in relative MI region myocardial blood flow compared with the MI-saline group and improved myocardial strain in the MI region. CONCLUSIONS We have established a novel hybrid single-photon emission computed tomography/computed tomography imaging approach for the quantitative assessment of regional MMP activation, myocardial blood flow, and cardiac function post-I/R that can be used to evaluate therapeutic interventions such as intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases of post-MI remodeling.

中文翻译：

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应用混合基质金属蛋白酶靶向动态 201Tl 单光子发射计算机断层扫描/计算机断层扫描成像评估早期心肌梗死后重塑。

背景技术基质金属蛋白酶（MMP）的诱导和MMP组织抑制剂（TIMP）的减少在心肌梗塞（MI）后的缺血/再灌注（I/R）损伤和随后的左心室重构中发挥作用。我们开发了一种混合双同位素单光子发射计算机断层扫描/计算机断层扫描方法，用于无创评估区域心肌 MMP 激活，使用 99mTc-RP805 和动态 201Tl 测定心肌血流量，以量化重组 TIMP-3 冠状动脉内递送的影响(rTIMP-3) 对 I/R 损伤的影响。方法 在对照猪 (n=5) 和 90 分钟球囊闭塞诱导左前降支缺血/再灌注 (I/R) 后的猪 (n=9) 中进行研究。再灌注前，患有 I/R 的猪被随机分配至冠状动脉内输注 rTIMP-3 (1.0 mg/kg；n=5) 或盐水 (n=4)。I/R 三天后，使用 99mTc-RP805 和 201Tl 以及对比 cineCT 进行双同位素成像，以评估左心室功能。结果生理盐水组I/R后99mTc-RP805的缺血与非缺血比率显着增加（4.03±1.40），而rTIMP-3治疗后该比率显着降低（2.22±0.57；P=0.03）。MI-rTIMP-3治疗组中MMP活性的降低与MI-盐水组相比相对MI区域心肌血流量的改善以及MI区域心肌应变的改善相关。结论 我们建立了一种新型混合单光子发射计算机断层扫描/计算机断层扫描成像方法，用于定量评估局部 MMP 激活、心肌血流量和 I/R 后心脏功能，可用于评估冠状动脉内介入治疗等治疗干预措施递送 rTIMP-3 可减少 MI 后重塑早期阶段的 I/R 损伤。