Hook S, Caple J F, McMahon J T, Myles J L, Ratliff N B
Department of Anatomic Pathology, Cleveland Clinic Foundation, OH 44195, USA.
J Heart Lung Transplant. 1995 Mar-Apr;14(2):351-8.
Myocyte necrosis has been cited as a key feature in the diagnosis and classification of both moderate and severe acute cellular rejection (International Society for Heart and Lung Transplantation grades 3A to 4). However, our previous work suggests that myocyte necrosis is not a typical feature of cellular rejection.
To clarify this point and to elucidate differences between cellular rejection and acute vascular rejection, we compared the light and electron microscopic features of 35 consecutive endomyocardial biopsy specimens from six patients with acute vascular rejection diagnosed with positive immunofluorescence, 12 consecutive endomyocardial biopsy specimens from three patients with mixed acute vascular rejection and cellular rejection, and 435 endomyocardial biopsy specimens of International Society for Heart and Lung Transplantation grades 2 to 4 cellular rejection.
Endomyocardial biopsy specimens from eight of nine patients with acute vascular rejection and mixed acute vascular rejection/cellular rejection exhibited classic myocyte necrosis as the typical form of myocardial cell injury. Myocyte necrosis was characterized by lysis of the sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cell injury in cellular rejection was reversible. Reversible cellular rejection was characterized by extensive loss of myosin filaments and Z-lines with subsarcolemmal and intracytoplasmic accumulation of Z-band material. Cell swelling, mitochondrial swelling, intramitochondrial densities, and lysis of sarcolemma were not observed.
We conclude that myocyte necrosis is a characteristic feature of acute vascular rejection, whereas reversible myocardial cell injury is characteristic of cellular rejection, including grade 4. Myocyte necrosis is not a feature of cellular rejection. The presence of true myocyte necrosis in endomyocardial biopsy specimens from cyclosporine-treated heart transplants implicates some process other than cellular rejection. Processes producing myocyte necrosis include acute vascular rejection, peritransplantation ischemia, and accelerated atherosclerosis.
心肌细胞坏死一直被认为是中度和重度急性细胞排斥反应（国际心肺移植学会3A至4级）诊断和分类的关键特征。然而，我们之前的研究表明，心肌细胞坏死并非细胞排斥反应的典型特征。
为阐明这一点并明确细胞排斥反应与急性血管排斥反应之间的差异，我们比较了6例经免疫荧光检查确诊为急性血管排斥反应患者的35份连续心内膜心肌活检标本、3例混合性急性血管排斥反应和细胞排斥反应患者的12份连续心内膜心肌活检标本以及国际心肺移植学会2至4级细胞排斥反应的435份心内膜心肌活检标本的光镜和电镜特征。
9例急性血管排斥反应及混合性急性血管排斥反应/细胞排斥反应患者中的8例的心内膜心肌活检标本显示，典型的心肌细胞损伤形式为经典的心肌细胞坏死。心肌细胞坏死的特征为肌膜溶解、线粒体明显肿胀以及线粒体内出现絮状致密物。相比之下，细胞排斥反应中心肌细胞损伤的典型形式是可逆的。可逆性细胞排斥反应的特征为肌球蛋白丝和Z线广泛丢失，Z带物质在肌膜下和胞质内积聚。未观察到细胞肿胀、线粒体肿胀、线粒体内致密物以及肌膜溶解。
我们得出结论，心肌细胞坏死是急性血管排斥反应的特征性表现，而可逆性心肌细胞损伤是细胞排斥反应（包括4级）的特征性表现。心肌细胞坏死并非细胞排斥反应的特征。在接受环孢素治疗的心脏移植患者的心内膜心肌活检标本中出现真正的心肌细胞坏死意味着存在细胞排斥反应以外的其他过程。导致心肌细胞坏死的过程包括急性血管排斥反应、移植围手术期缺血以及加速性动脉粥样硬化。
