腺苷应激 T1 映射的分子机制。
Molecular Mechanisms of Adenosine Stress T1 Mapping.
机构信息
Department of Biomedical Engineering (S.A.S., C.E.R., B.A.F., F.H.E.), University of Virginia, Charlottesville, VA.
Department of Radiology (B.A.F., F.H.E.), University of Virginia, Charlottesville, VA.
出版信息
Circ Cardiovasc Imaging. 2021 Mar;14(3):e011774. doi: 10.1161/CIRCIMAGING.120.011774. Epub 2021 Mar 12.
BACKGROUND
Adenosine stress T1 mapping is an emerging magnetic resonance imaging method to investigate coronary vascular function and myocardial ischemia without application of a contrast agent. Using gene-modified mice and 2 vasodilators, we elucidated and compared the mechanisms of adenosine myocardial perfusion imaging and adenosine T1 mapping.
METHODS
Wild-type (WT), AAR (adenosine A receptor knockout), AAR (adenosine A receptor knockout), AAR (adenosine A receptor knockout), and eNOS (endothelial nitric oxide synthase knockout) mice underwent rest and stress perfusion magnetic resonance imaging (n=8) and T1 mapping (n=10) using either adenosine, regadenoson (a selective AAR agonist), or saline. Myocardial blood flow and T1 were computed from perfusion imaging and T1 mapping, respectively, at rest and stress to assess myocardial perfusion reserve and T1 reactivity (ΔT1). Changes in heart rate for each stress agent were also calculated. Two-way ANOVA was used to detect differences in each parameter between the different groups of mice.
RESULTS
Myocardial perfusion reserve was significantly reduced only in AAR compared to WT mice using adenosine (1.06±0.16 versus 2.03±0.52, <0.05) and regadenoson (0.98±026 versus 2.13±0.75, <0.05). In contrast, adenosine ΔT1 was reduced compared with WT mice (3.88±1.58) in both AAR (1.63±1.32, <0.05) and AAR (1.55±1.35, <0.05). Furthermore, adenosine ΔT1 was halved in eNOS (1.76±1.46, <0.05) versus WT mice. Regadenoson ΔT1 was approximately half of adenosine ΔT1 in WT mice (1.97±1.50, <0.05), and additionally, it was significantly reduced in eNOS mice (-0.22±1.46, <0.05). Lastly, changes in heart rate was 2× greater using regadenoson versus adenosine in all groups except AAR, where heart rate remained constant.
CONCLUSIONS
The major findings are that (1) although adenosine myocardial perfusion reserve is mediated through the A receptor, adenosine ΔT1 is mediated through the A and A receptors, (2) adenosine myocardial perfusion reserve is endothelial independent while adenosine ΔT1 is partially endothelial dependent, and (3) ΔT1 mediated through the A receptor is endothelial dependent while ΔT1 mediated through the A receptor is endothelial independent.
背景
腺苷应激 T1 映射是一种新兴的磁共振成像方法，可用于研究冠状动脉功能和心肌缺血，而无需使用造影剂。使用基因修饰的小鼠和 2 种血管扩张剂，我们阐明并比较了腺苷心肌灌注成像和腺苷 T1 映射的机制。
方法
在 rest 和 stress 状态下，对野生型（WT）、AAR（腺苷 A 受体敲除）、AAR（腺苷 A 受体敲除）、AAR（腺苷 A 受体敲除）和 eNOS（内皮型一氧化氮合酶敲除）小鼠进行磁共振灌注成像（n=8）和 T1 映射（n=10），使用腺苷、regadenoson（一种选择性 AAR 激动剂）或生理盐水。通过灌注成像和 T1 映射分别计算心肌血流和 T1，以评估心肌灌注储备和 T1 反应性（ΔT1）。还计算了每种应激剂引起的心率变化。采用双因素方差分析检测不同小鼠组之间每个参数的差异。
结果
仅在使用腺苷和 regadenoson 时，与 WT 小鼠相比，AAR 小鼠的心肌灌注储备显著降低（分别为 1.06±0.16 与 2.03±0.52，<0.05；0.98±026 与 2.13±0.75，<0.05）。相比之下，与 WT 小鼠相比，AAR 小鼠的腺苷 ΔT1 降低（3.88±1.58）（AAR 为 1.63±1.32，<0.05；AAR 为 1.55±1.35，<0.05）。此外，eNOS 小鼠的腺苷 ΔT1 降低至 WT 小鼠的一半（1.76±1.46，<0.05）。与 WT 小鼠相比，regadenoson ΔT1 约为腺苷 ΔT1 的一半（1.97±1.50，<0.05），并且在 eNOS 小鼠中，其值显著降低（-0.22±1.46，<0.05）。最后，除了 AAR 组之外，所有组中使用 regadenoson 引起的心率变化均为使用腺苷的 2 倍，而 AAR 组的心率保持不变。
结论
主要发现是：（1）尽管腺苷心肌灌注储备通过 A 受体介导，但腺苷 ΔT1 通过 A 和 A 受体介导；（2）腺苷心肌灌注储备不受内皮影响，而腺苷 ΔT1 部分依赖内皮；（3）通过 A 受体介导的 ΔT1 依赖内皮，而通过 A 受体介导的 ΔT1 不受内皮影响。
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