Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model
Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model
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DOI：
10.1161/01.cir.0000115586.25803.d5
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发表时间：
2004-03-02
期刊：
影响因子：
37.8
通讯作者：
Kohno, M
中科院分区：
文献类型：
--
作者：
Kondo, I;Ohmori, K;Kohno, M
背景-重复的肌内膜活检对监测心脏移植后免疫抑制剂的作用是必要的.微泡靶向白细胞的超声造影检测急性白细胞浸润。我们研究了白细胞靶向心肌造影超声心动图（MCE）是否可以提供定量评估急性心脏排斥反应。方法和结果-心脏从布朗挪威大鼠或刘易斯大鼠移植到其他布朗挪威大鼠。同种移植物和未处理或用低剂量（3 mg . kg（-1）。d（-1））或高剂量（10 mg . kg（-1）。d（-1）），移植后第3天进行比较。超声心动图显示的左室壁增厚在4组之间相当。心肌血流与MCE评估，脉冲间隔与信号强度（SI），仅在未经处理的同种异体移植物略有下降。然而，心肌SI在这些组中，在注射造影剂后允许微泡-白细胞相互作用的10分钟时间段后获得的（灰度级）显示出明显的梯度（在未处理的同种异体移植物中为12 +/-2，在用低剂量CsA处理的同种异体移植物中为9 +/-5，在用高剂量CsA处理的同种异体移植物中为6 +/-3，在同种异体移植物中为2 +/-1，P < 0.001）。各组间SI的差异与艾德1阳性细胞的SI差异一致（巨噬细胞）计数（每个高倍视野分别为25 +/- 7、12 +/- 4、5 +/- 3和1 +/- 0个细胞，P < 0.001），这与CD 3阳性细胞相关（T淋巴细胞）计数（每个高倍视野分别为33 +/-5，22 +/-5，9 +/-4和1 +/-0个细胞，P < 0.001）。结论-白细胞-靶向MCE可以通过直接显示心肌内巨噬细胞和T细胞浸润的程度，淋巴细胞
Background - Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte- targeted myocardial contrast echocardiography ( MCE) could provide for the quantitative assessment of acute cardiac rejection.Methods and Results - Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A ( CsA) at a low dose ( 3 mg . kg(-1) . d(-1)) or high dose (10 mg . kg(-1) . d(-1)) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography- derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity ( SI), was slightly decreased only in untreated allografts. However, myocardial SI ( in gray levels) obtained after a 10- minute period allowing microbubble - leukocyte interactions after contrast injection exhibited a clear gradient in these groups ( 12 +/- 2 in untreated allografts, 9 +/- 5 in allografts treated with low- dose CsA, 6 +/- 3 in allografts treated with high- dose CsA, and 2 +/- 1 in isografts, P < 0.001). The pattern of difference in SI among the groups agreed well with that in ED- 1 - positive cell ( macrophage) count ( 25 +/- 7, 12 +/- 4, 5 +/- 3, and 1 +/- 0 cells per high- power field, respectively, P < 0.001), which correlated with CD3- positive cell ( T lymphocyte) count ( 33 +/- 5, 22 +/- 5, 9 +/- 4, and 1 +/- 0 cells per high- power field, respectively, P < 0.001).Conclusions - Leukocyte- targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.