In vivo characterization of murine myocardial perfusion with myocardial contrast echocardiography - Validation and application in nitric oxide synthase 3-deficient mice
In vivo characterization of murine myocardial perfusion with myocardial contrast echocardiography - Validation and application in nitric oxide synthase 3-deficient mice
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DOI：
10.1161/circulationaha.107.707737
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发表时间：
2007-09-11
期刊：
影响因子：
37.8
通讯作者：
Scherrer-Crosbie, Marielle
中科院分区：
文献类型：
--
作者：
Raher, Michael J.;Thibault, Helene;Scherrer-Crosbie, Marielle
背景-在体内非侵入性评估小鼠心肌血流量（MBF）的能力将为心血管研究提供一个重要的工具。心肌造影超声心动图（MCE）已被用于测量MBF，但尚未在小鼠中验证。本研究评估MCE是否可以评估静息和血管舒张后的MBF，并测量小鼠MBF的最大增加（冠状动脉储备）。研究了野生型（WT）和一氧化氮合酶3（NOS 3）缺陷型（NOS 3（-/-））小鼠。方法和结果-MCE在基线和静脉输注乙酰胆碱或腺苷后进行。输注去甲肾上腺素造影剂，并以实时模式采集胸骨旁视图。获得心肌对比剂的补充曲线，并计算信号上升率（β）和平台强度（A）。用A和β的乘积（A β）估算的MBF与用荧光微球测量的MBF进行比较。MCE分析在98%（52/53）的小鼠中可行。微球测得的MBF随腺苷增加而增加，并与A β密切相关。WT和NOS 3（-/-）小鼠在休息时MCE衍生的MBF没有差异。腺苷输注使NOS 3（-/-）小鼠的MBF增加3.0 +/- 0.6倍，WT增加2.5 +/- 0.3倍（基因型之间P = 0.58）。乙酰胆碱在WT小鼠中诱导MBF增加2.4 +/-0.2倍，但在NOS 3（-/-）小鼠中不增加MBF（相对于WT，P < 0.0005）。结论：心肌声学造影可以准确地评价完整小鼠的心肌血流量、冠状动脉储备和血管舒张反应。该方法证明了与WT小鼠相比，NOS 3（-/-）小鼠对腺苷的冠状动脉反应保留，但乙酰胆碱诱导的血管舒张受损。
Background-The ability to noninvasively evaluate murine myocardial blood flow (MBF) in vivo would provide an important tool for cardiovascular research. Myocardial contrast echocardiography (MCE) has been used to measure MBF; however, it has not been validated in mice. This study assesses whether MCE can evaluate MBF at rest and after vasodilation and measure the maximal augmentation ( coronary reserve) of MBF in mice. Wild-type (WT) and nitric oxide synthase 3 (NOS3)-deficient (NOS3(-/-) ) mice were studied. Methods and Results-MCE was performed at baseline and after intravenous infusion of acetylcholine or adenosine. Definity contrast agent was infused, and parasternal views were acquired in real-time mode. Replenishment curves of myocardial contrast were obtained, and rates of signal rise (beta) and plateau intensity ( A) were calculated. MBF estimated by the product of A and beta ( A beta) was compared with that measured with fluorescent microspheres. MCE analysis was feasible in 98% ( 52/53) of mice. MBF measured by microspheres increased with adenosine and correlated closely with A beta. There was no difference in MCE-derived MBF between WT and NOS3 (-/-) mice at rest. Adenosine infusion increased MBF by 3.0 +/- 0.6-fold in NOS3 (-/-) mice and 2.5 +/- 0.3-fold in WT ( P = 0.58 between genotypes). Acetylcholine induced an increase of 2.4 +/- 0.2-fold in MBF in WT mice but did not increase MBF in NOS3 (-/-) mice ( P < 0.0005 versus WT). Conclusions-MBF, coronary reserve, and vasodilator responses can be evaluated accurately in the intact mouse by MCE. This method demonstrated a preserved coronary response to adenosine but an impaired acetylcholine-induced vasodilation in NOS3 (-/-) mice compared with WT mice.