Smith Brendon W, Simpson Douglas G, Sarwate Sandhya, Miller Rita J, Erdman John W, O'Brien William D
Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (B.W.S., S.S., R.J.M., W.D.O.), Division of Nutritional Sciences (B.W.S., J.W.E., W.D.O.), and Departments of Statistics (D.G.S.), Pathology (S.S.), and Food Science and Human Nutrition (J.W.E.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA.
J Ultrasound Med. 2015 Jun;34(6):1115-22. doi: 10.7863/ultra.34.6.1115.
Ultrasound contrast agents (UCAs) enhance cardiovascular ultrasound imaging. Adverse biological effects have occurred after administration of UCAs, and more research is needed for a comprehensive understanding of the risks involved. We used the ApoE(-/-) mouse model of atherosclerosis to characterize the effects of ultrasound and UCAs on atherosclerosis and plasma biomarkers.
Male ApoE(-/-) mice (8 weeks old; n = 24) were intravenously infused with a UCA (2 × 10(10) Definity microbubbles per hour; Lantheus Medical Imaging, North Billerica, MA) and exposed to 2.8-MHz center frequency ultrasound (10 Hz pulse repetition frequency, 1.4 microseconds pulse duration, 2 minutes exposure duration, and 2 sites) at 1 of 3 derated peak rarefactional pressure amplitudes (0, 1.9, or 3.8 MPa), and then consumed either a chow or Western diet for 4 weeks (n = 4 per group). Blood plasma samples were collected before ultrasound exposure and at 2 and 4 weeks after exposure and assayed for total cholesterol and von Willebrand Factor (vWF). A pathologist measured atheroma thickness in formalin-fixed, hematoxylin-eosin-stained transverse aorta sections and scored them for severity of atherosclerosis.
Plasma total cholesterol initially averaged 286 mg/dL in the Western diet group and increased to 861 mg/dL after 4 weeks on the diet (P < .0001). Total cholesterol did not increase significantly in the chow diet group. Plasma vWF increased after 2 weeks on the Western diet (P < .0001). Atheroma thickness was greater in animals consuming the Western diet than in chow-fed animals (P < .05). Ultrasound had no significant effect on plasma total cholesterol, plasma vWF, or atheroma thickness.
Contrast ultrasound did not increase the severity of atherosclerosis or alter cardiovascular biomarkers in the ApoE(-/-) mouse model.
超声造影剂（UCA）可增强心血管超声成像。UCA给药后出现了不良生物学效应，需要更多研究以全面了解其中涉及的风险。我们使用动脉粥样硬化的ApoE（-/-）小鼠模型来表征超声和UCA对动脉粥样硬化和血浆生物标志物的影响。
将雄性ApoE（-/-）小鼠（8周龄；n = 24）静脉内注入UCA（每小时2×10¹⁰个Definity微泡；Lantheus Medical Imaging，马萨诸塞州北比勒里卡），并在3个降额峰值稀疏压力幅度（0、1.9或3.8 MPa）之一的条件下，暴露于2.8 MHz中心频率超声（10 Hz脉冲重复频率、1.4微秒脉冲持续时间、2分钟暴露持续时间和2个部位），然后食用普通饲料或西式饮食4周（每组n = 4）。在超声暴露前以及暴露后2周和4周采集血浆样本，测定总胆固醇和血管性血友病因子（vWF）。病理学家在福尔马林固定、苏木精-伊红染色的主动脉横切片中测量动脉粥样硬化斑块厚度，并对动脉粥样硬化的严重程度进行评分。
西式饮食组血浆总胆固醇最初平均为286 mg/dL，饮食4周后增至861 mg/dL（P <.0001）。普通饮食组总胆固醇没有显著增加。西式饮食2周后血浆vWF升高（P <.0001）。食用西式饮食的动物的动脉粥样硬化斑块厚度大于食用普通饲料的动物（P <.05）。超声对血浆总胆固醇、血浆vWF或动脉粥样硬化斑块厚度没有显著影响。
在ApoE（-/-）小鼠模型中，超声造影并未增加动脉粥样硬化的严重程度或改变心血管生物标志物。
