Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent

Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent
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DOI:
10.1016/s0735-1097(01)01759-4
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发表时间:
2002-02-06
影响因子:
24
通讯作者:
Kaul, S
Kaul, S
中科院分区:
医学1区
文献类型:
--
作者:
Fisher, NG;Christiansen, JP;Kaul, S

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目的研究新型第三代超声造影剂BR14的心肌和微血管动力学。这一发现的机制尚不清楚。方法9只单支冠状动脉非严重狭窄的开胸犬在冠状动脉充血时静脉推注BR14。在正常床和狭窄床上绘制时间-声强(AI)图,用放射性标记微球测量心肌血流量(MBF)。对11只野生型小鼠的外提睾肌进行活体显微镜观察。结果在峰值对比增强时,狭窄床和正常床的AI比值为0.44+/-0.23,与放射性标记微球来源的两床的MBF比值(0.45+/-0.20)相近。在注射后400时,尽管MBF没有变化,但两床之间的AI比率接近于1(0.99+/-0.07),表明药物重新分布。BR14的心肌动力学可用修正的滞后正常密度函数来描述。估计只有3%的给药微泡保留在心肌中。活体显微镜显示大多数气泡仅短暂滞留在毛细血管内(S 2~3个)。结论BR14由于暂时性滞留在毛细血管内而发生再分布。因此,与TL-201类似,它有可能用于检测应激期间单次注射后的冠状动脉狭窄和心肌存活。(C)2002年,由美国心脏病学会提供。
OBJECTIVES This study sought to investigate the myocardial and microvascular kinetics of BR14, a novel third-generation ultrasound contrast agent.BACKGROUND BR14 produces persistent myocardial opacification after the administration of a single intravenous bolus when the left ventricular cavity contrast has considerably diminished. The mechanism of this finding is unknown.METHODS Nine open-chest dogs with non-critical stenosis of a single coronary artery were given intravenous bolus injections of BR14 during coronary hyperemia. Time versus acoustic intensity (AI) plots were generated from the normal and stenosed beds and myocardial blood flow (MBF) was measured with radiolabeled microspheres. Intravital microscopy was performed on an exteriorized cremaster muscle in 11 wild-type mice to study the microvascular kinetics of the agent.RESULTS At peak contrast enhancement, the ratio between AI in the stenosed and normal bed was 0.44 +/- 0.23, which was similar to the radiolabeled microsphere-derived MBF ratio between the two beds (0.45 +/- 0.20). At 400 s after injection, the AI ratio between the two beds approximated unity (0.99 +/- 0.07) despite no changes in MBF, indicating redistribution of the agent. The myocardial kinetics of BR14 was best characterized by a modified lagged normal density function. Only about 3% of administered microbubbles were estimated to be retained in the myocardium. Intravital microscopy showed that most of these bubbles were retained only transiently (2 to 3 s) within capillaries.CONCLUSIONS BR14 demonstrates redistribution because of transient retention within capillaries. Therefore, similar to Tl-201, it could potentially be used to detect both coronary stenosis and myocardial viability after a single injection during stress. (C) 2002 by the American College of Cardiology.