Rubin P J, Hartman J J, Hasapes J P, Bakke J E, Bergmann S R
Cardiovascular Division, Washington University School of Medicine, St Louis, Mo, USA.
Circulation. 1996 Nov 1;94(9 Suppl):II298-303.
Cardiac transplantation is an increasingly important treatment for patients with end-stage heart failure. Rejection is one of the major limitations, and currently, serial endomyocardial biopsies are required to diagnose rejection. In the year after transplantation, patients routinely undergo 12, 14, or more biopsies. Infiltration of lymphocytes into the graft is a central feature of rejection. Previous studies from our laboratory have demonstrated the feasibility of detecting early rejection noninvasively with gamma scintigraphy after administration of autologous lymphocytes labeled with 111In.
Eight patients were studied at the time of routine biopsy an average of 4.5 months after cardiac transplantation. Autologous lymphocytes were isolated and labeled with 111In. Forty-eight to 72 hours later, patients underwent planar scintigraphic imaging. Myocardial accumulation of labeled lymphocytes was quantified (indium excess, IE) with a previously described and validated technique. Animal studies have shown that an IE > or = 0.07 is associated with rejection. Two of four patients with biopsy grade 0 or 1A rejection had no excess accumulation of labeled lymphocytes. The other two patients with biopsy grade 0 or 1A had an average IE of 0.13 +/- 0.04 (SD), which may actually represent the higher sensitivity of the scintigraphic approach, since the whole myocardium is interrograted. All four patients with biopsy grade 1B rejection had increased accumulation of labeled lymphocytes (IE = 0.18 +/- 0.06, P = .06 compared with all patients with grade 0 or 1A biopsies).
The development of a sensitive, specific, and noninvasive method of diagnosing cardiac allograft rejection in humans might obviate the need for endomyocardial biopsy as well as improve the accuracy of diagnosis. The results suggest that scintigraphic detection of labeled lymphocytes is a promising approach for the noninvasive detection of cardiac transplant rejection. In addition, the approach should permit the assessment of the efficacy of antirejection therapy.
心脏移植对于终末期心力衰竭患者而言，正成为一种愈发重要的治疗手段。排斥反应是主要限制因素之一，目前需要通过系列心内膜心肌活检来诊断排斥反应。在移植后的第一年，患者通常要接受12次、14次或更多次活检。淋巴细胞浸润到移植物中是排斥反应的核心特征。我们实验室之前的研究已经证明，在注射用111铟标记的自体淋巴细胞后，通过γ闪烁显像术无创检测早期排斥反应是可行的。
对8例患者进行了研究，这些患者在心脏移植后平均4.5个月时接受常规活检。分离出自体淋巴细胞并用111铟进行标记。48至72小时后，患者接受平面闪烁显像。用先前描述并验证过的技术对标记淋巴细胞在心肌中的蓄积进行定量（铟过量，IE）。动物研究表明，IE≥0.07与排斥反应相关。4例活检为0级或1A级排斥反应的患者中有2例标记淋巴细胞没有过量蓄积。另外2例活检为0级或1A级的患者平均IE为0.13±0.04（标准差），这实际上可能代表了闪烁显像方法更高的敏感性，因为整个心肌都被检测了。4例活检为1B级排斥反应的患者标记淋巴细胞蓄积均增加（IE = 0.18±0.06，与所有活检为0级或1A级的患者相比，P = 0.06）。
开发一种敏感、特异且无创的诊断人类心脏同种异体移植排斥反应的方法，可能无需进行心内膜心肌活检，同时还能提高诊断准确性。结果表明，闪烁显像检测标记淋巴细胞是无创检测心脏移植排斥反应的一种有前景的方法。此外，该方法应能评估抗排斥治疗的疗效。
