Kondo Isao, Ohmori Koji, Oshita Akira, Takeuchi Hiroto, Yoshida Junji, Shinomiya Kaori, Fuke Sachiko, Suzuki Takeo, Mizushige Katsufumi, Kohno Masakazu
Second Department of Internal Medicine, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
Circulation. 2004 Mar 2;109(8):1056-61. doi: 10.1161/01.CIR.0000115586.25803.D5. Epub 2004 Feb 16.
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.
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 x kg(-1) x d(-1)) or high dose (10 mg x kg(-1) x 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).
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.
心脏移植后，需要反复进行心内膜心肌活检以监测免疫抑制剂的效果。靶向白细胞的微泡对比超声可检测急性白细胞浸润。我们研究了靶向白细胞的心肌对比超声心动图（MCE）是否能够对急性心脏排斥反应进行定量评估。
将来自棕色挪威大鼠或刘易斯大鼠的心脏移植到其他棕色挪威大鼠体内。比较移植后第3天的同基因移植以及未处理的同种异体移植组，或移植前3天接受低剂量（3mg·kg⁻¹·d⁻¹）或高剂量（10mg·kg⁻¹·d⁻¹）环孢素A（CsA）治疗的同种异体移植组。4组之间超声心动图测得的左心室壁增厚情况相当。通过MCE评估心肌血流，将脉冲间隔与信号强度（SI）相关联，仅未处理的同种异体移植组心肌血流略有下降。然而，在注射造影剂后经过10分钟使微泡与白细胞相互作用后获得的心肌SI（灰度级）在这些组中呈现出明显的梯度（未处理的同种异体移植组为12±2，低剂量CsA治疗的同种异体移植组为9±5，高剂量CsA治疗的同种异体移植组为6±3，同基因移植组为2±1，P<0.001）。各组之间SI的差异模式与ED-1阳性细胞（巨噬细胞）计数的差异模式非常吻合（分别为每高倍视野25±7、12±4、5±3和1±0个细胞，P<0.001），且与CD3阳性细胞（T淋巴细胞）计数相关（分别为每高倍视野33±5、22±5、9±4和1±0个细胞，P<0.001）。
靶向白细胞的MCE可通过直接揭示心肌内巨噬细胞和T淋巴细胞浸润的程度，对移植心脏的排斥程度进行无创评估。
